Bone Augmentation In Implant Dentistry MICHAEL A. PIKOS, Richard J. Miron

Nha khoa cấy ghép Implant đã phát triển vượt bậc trong ba thập kỷ qua và đang nhanh chóng tiến bộ khi các vật liệu và quy trình mới ra đời. Mặc dù vật liệu sinh học và các hướng dẫn lâm sàng từng được cho là sẽ thay đổi sau mỗi 3 đến 5 năm, nhưng những tiến bộ mới hiện đang được đưa vào lĩnh vực của chúng tôi hàng năm. Ngày nay, nha khoa cấy ghép implant có lẽ là chuyên ngành được nghiên cứu rộng rãi nhất trong lĩnh vực của chúng tôi và nhiệm vụ của các bác sĩ là phải cập nhật các xu hướng và quy trình hiện hành. Với số lượng tiến bộ được thực hiện trong phương tiện truyền thông và tiếp thị dựa trên kỹ thuật số, bác sĩ lâm sàng bắt buộc phải có khả năng tách các xu hướng mới khỏi các giao thức dựa trên bằng chứng. Không nghi ngờ gì khi mục tiêu của mọi bác sĩ lâm sàng là mỗi bệnh nhân được điều trị với kết quả tốt nhất có thể trong tâm trí. Do đó, chúng ta nên cố gắng thực hiện các quyết định dựa trên bằng chứng hợp lý dựa trên các tài liệu hiện có để cho phép chúng ta đưa ra các lựa chọn đúng đắn và có thể dự đoán được. Mục tiêu của cuốn sách này là chia sẻ kinh nghiệm lâm sàng của tôi, cả thành công và thất bại, với các đồng nghiệp của tôi để tạo điều kiện học tập thông qua các trường hợp được ghi lại mà tôi đã thực hiện trong hơn 35 năm qua. Để thực hiện điều này, cuốn sách giáo khoa này đã được tách thành sáu chương cốt lõi. Mỗi ca lâm sàng được bổ sung với các ghi chú cá nhân được in nghiêng mô tả kinh nghiệm học được từ từng ca, các thủ thuật lâm sàng và ngọc trai từ ca đó, các ghi chú kỹ thuật hướng tới việc tạo điều kiện cho người đọc khả năng lâm sàng thực hiện các ca ​​kỹ thuật tương tự, cũng như phân tích chuyên sâu và đánh giá quan trọng về cách tôi sẽ thực hiện từng trường hợp hôm nay (nhiều trường hợp đã được thực hiện hơn 10 năm trước). Hai chương dành riêng cho vật liệu sinh học và dụng cụ được sử dụng cho các quy trình nâng xương và tạo cơ sở cho vật liệu sinh học và dụng cụ phẫu thuật được sử dụng trong suốt các chương phẫu thuật. Rõ ràng là số lượng thay đổi được thực hiện trong thiết kế vật liệu thiết bị đo đạc đã tạo điều kiện (và trong nhiều trường hợp được cải thiện) khả năng thực hiện các thủ thuật phẫu thuật của các bác sĩ lâm sàng. Song song với điều này và không kém phần quan trọng, rất nhiều tiến bộ đã được thực hiện trong khoa học vật liệu sinh học. Trong khi vật liệu sinh học từng được coi là vật liệu cấu trúc thụ động nhằm lấp đầy các khoảng trống, ngày nay chúng hoạt động như các phân tử hoạt tính sinh học chịu trách nhiệm kích thích nhanh chóng tái tạo mô mới. Chương 2 trình bày về màng chắn, vật liệu ghép xương, cũng như các yếu tố tăng trưởng được sử dụng cho các quy trình nâng xương và mô tả nền tảng sinh học và ứng dụng lâm sàng của chúng trong nha khoa cấy ghép. Chương 3 là chương phẫu thuật đầu tiên và dành riêng cho việc quản lý ổ chiết. Tổng quan ngắn gọn về những thay đổi kích thước xảy ra sau đoạn văn được trình bày và sau đó sẽ đề cập đến các hướng dẫn lâm sàng với các quy trình từng bước. Thảo luận về việc sử dụng các vật liệu sinh học khác nhau và khả năng giảm thiểu sự thay đổi kích thước của chúng sau khi tiếp nhận ở cả khu vực thẩm mỹ và không gây mê được đưa ra. Hơn nữa, các quy trình bảo tồn sườn núi trong trường hợp không có đĩa đệm ngôn ngữ được bao gồm cũng như giới thiệu về khái niệm và chỉ định lâm sàng cho liệu pháp SOCKET SHIELD”. Chương 4 bao gồm chủ đề về sự tăng sinh của phế nang. Các chỉ định cụ thể và mô tả các tiêu chí lựa chọn bệnh nhân, quy trình phẫu thuật từng bước và các khía cạnh của điều trị sau phẫu thuật được trình bày. Chương này cũng bao gồm thông tin cơ bản về tái tạo xương có hướng dẫn, các kỹ thuật lấy xương trong khoang, các quy trình nâng cao xương sống theo chiều ngang và dọc ở các vùng sau và trước hàm trên hàm dưới, kỹ thuật tách xương sống và tạo hình tiền đình. Nhiều phức tạp phải đối mặt trong bất kỳ quy trình nào nêu trên cũng được thảo luận với các giải pháp cho những khó khăn như vậy. Chương 5 tập trung vào ghép xoang. Đầu tiên, lịch sử ghép xoang được trình bày tổng quan về những cân nhắc giải phẫu. Đánh giá lâm sàng và chụp X quang sau đó được xem xét với thảo luận chi tiết về giao thức cửa sổ bên so với giao thức crestal được sử dụng cho các chỉ định lâm sàng cụ thể. Phần nhấn mạnh trong chương này bao gồm thiết bị đo để ghép xoang, thiết kế đường rạch và quản lý vạt, lựa chọn và đặt mảnh ghép, sử dụng công nghệ thông khí hóa, cũng như các quy trình để sửa chữa màng xoang. Cả hai quy trình một giai đoạn và hai giai đoạn đều được thảo luận với các trường hợp được chỉ định cho các cung răng một hàm, nhiều răng và toàn hàm. Phần cuối cùng của chương này trình bày nhiều biến chứng tiềm ẩn phải đối mặt trong quá trình ghép xoang và cách giải quyết của chúng. Cuối cùng, chương 6 bao gồm việc tái thiết toàn bộ vòm bằng cách sử dụng các giao thức chuyển đổi thông thường và các giao thức tái tạo ngay lập tức được hướng dẫn đầy đủ mới hơn theo cách chi tiết từng bước bằng cách sử dụng công nghệ được cấp bằng sáng chế nSequence. Tôi hy vọng rằng thông qua nhiều trường hợp được trình bày trong cuốn sách này, các bác sĩ lâm sàng sẽ có thể thực hiện tốt hơn các quyết định lâm sàng dựa trên bằng chứng dẫn đến kết quả nâng xương có thể dự đoán được và thành công lâu dài. Chúng ta đang sống trong thời đại mà thông tin có thể được thu thập thông qua mạng xã hội với tốc độ ngày càng cao. Các bác sĩ lâm sàng hiện có thể tự do đăng các trường hợp trực tiếp lên mạng xã hội sau khi phẫu thuật và nhận được phản hồi gần như trực tiếp về công việc của họ. Điều này cung cấp cho bác sĩ lâm sàng và người đọc những phản hồi trực tiếp đối với công việc phẫu thuật của họ; tuy nhiên, với số lượng các kỹ thuật và giao thức mới được sử dụng và quảng bá trực tuyến, vẫn khó để đánh giá và phê bình một cách khoa học nhiều giao thức mới hơn này nếu không có sự theo dõi lâu dài. Đã làm nha khoa cấy ghép implant hơn 35 năm, tôi coi thời gian theo dõi 1 năm, 5 năm và 10 năm là vô cùng quan trọng. Cuốn sách này tập trung hoàn toàn vào các quy trình đã được phát triển trong nhiều năm với những theo dõi lâu dài đã được thiết lập để cung cấp cho người đọc một tập hợp các hướng dẫn và nguyên tắc phẫu thuật với các kết quả dài hạn có thể dự đoán được. Hơn nữa, một loạt video trực tuyến có sẵn tại www.pikosonline.com sẽ bổ sung cho cuốn sách để hướng dẫn thêm cho bác sĩ lâm sàng các biểu diễn phẫu thuật được cung cấp trong thư viện giảng dạy trực tuyến của chúng tôi. Tôi thực sự hy vọng rằng những video này kết hợp với nội dung của cuốn sách này sẽ mang lại trải nghiệm học tập thú vị và tôi mong nhận được phản hồi trong tương lai của bạn.

with Richard J Miron, dds , ms c , p h d

A Step-by-Step Guide to Predictable Alveolar Ridge and Sinus Grafting

MICHAEL A PIKOS received his DDS from The Ohio State

University College of Dentistry, after which he completed an internship at Miami Valley Hospital and residency training in Oral & Maxillofacial Surgery at the University of Pittsburgh Montefiore Hospital He is a Diplomate of the American Board of Oral and Maxillofacial Surgery, the American Board

of Oral Implantology/Implant Dentistry, and the tional Congress of Oral Implantologists and a Fellow of the American College of Dentists He is also an adjunct assistant professor in the Department of Oral & Maxillofacial Sur- gery at The Ohio State University College of Dentistry and Nova Southeastern University College of Dental Medicine

Interna-Dr Pikos is on the editorial boards of several journals and

is a well-published author who has lectured extensively on dental implants in North and South America, Europe, Asia, and the Middle East He is the founder and CEO of the Pikos Institute Since 1990, he has been teaching advanced bone and soft tissue grafting courses with alumni that now number more than 3,400 from all 50 states and 43 countries Dr Pikos maintains a private practice limited exclusively to implant surgery in Trinity, Florida (www.pikosinstitute.com).

Graft Window

Sinus Augmentation

Extraction Site

Group Leader, The Miron Research Lab Lead Educator, Advanced PRF Education

Venice, Florida

A Step-by-Step Guide to Predictable Alveolar Ridge and Sinus Grafting

author

Title: Bone augmentation in implant dentistry / Michael A Pikos and

Richard J Miron

Description: Batavia, IL : Quintessence Publishing Co Inc, [2019] |

Includes bibliographical references and index

Identifiers: LCCN 2019005043 | ISBN 9780867158250 (hardcover)

Subjects: | MESH: Alveolar Ridge Augmentation methods | Bone

Regeneration | Bone Transplantation | Dental Implantation methods

Classification: LCC RK667.I45 | NLM WU 640 | DDC 617.6/93 dc23

LC record available at https://lccn.loc.gov/2019005043

97%

©2019 Quintessence Publishing Co, Inc

Quintessence Publishing Co Inc

411 N Raddant Rd

Batavia, IL 60510

www.quintpub.com

5 4 3 2 1

All rights reserved This book or any part thereof may not be reproduced, stored in a retrieval system, or transmitted in any

form or by any means, electronic, mechanical, photocopying, or otherwise, without prior written permission of the publisher

Editor: Leah Huffman

Design: Sue Zubek

Production: Angelina Schmelter

Printed in China

C ontents

1 2 3 4 5 6

INSTRUMENTATION FOR ALVEOLAR RIDGE

MEMBRANES, GRAFTING MATERIALS,

Implant dentistry has evolved tremendously over the past

three decades and is rapidly progressing as new materials

and protocols become available While biomaterials and

clinical guidelines were once believed to turn over every

3 to 5 years, new advancements are now being brought to

our field every year Today, implant dentistry is perhaps the

most widely researched discipline in our field and mandates

that clinicians stay updated on current trends and protocols

With the number of advancements made in digitally based

media and marketing, it is imperative that the clinician be able

to separate new trends from evidence-based protocols It is

without question that the goal of every clinician is that each

patient be treated with the best possible outcome in mind As

such, we should strive to implement rational evidence-based

decisions grounded on available literature to allow us to make

sound and predictable choices The goal of this textbook is to

share my clinical experiences, both successes and failures, with

my colleagues to facilitate learning through documented cases

that I have performed over the past 35+ years

To accomplish this, this textbook has been separated into six

core chapters Each clinical case is supplemented with italicized

personal notes describing learned experiences from each case,

clinical tips and pearls from that case, technical notes geared

toward facilitating the reader’s clinical ability to perform

simi-lar cases/techniques, as well as in-depth analysis and critical

evaluation on how I would perform each case today (many

of the cases were performed 10+ years ago) Two chapters are

dedicated to biomaterials and instruments utilized for bone

augmentation protocols and form the basis for the

bioma-terials and surgical instrumentation utilized throughout the

surgical chapters It is clear that the number of changes made

in material design/instrumentation has facilitated (and in many

cases improved) the ability of clinicians to perform surgical

procedures Parallel to this and equally as important, a great

deal of advancement has been made in biomaterial sciences

While biomaterials were once considered to act as a passive

structural material aimed at filling voids, today they act as

bioac-tive molecules responsible for rapidly stimulating new tissue

regeneration Chapter 2 presents barrier membranes, bone grafting materials, as well as growth factors utilized for bone augmentation procedures and describes their biologic back-ground and clinical use in implant dentistry

Chapter 3 is the first surgical chapter and is dedicated to extraction socket management A brief overview of dimen-sional changes occurring postextraction is presented, and there-after clinical guidelines with step-by-step protocols are covered

Discussion of the use of various biomaterials and their ability

to minimize dimensional changes postextraction in both the esthetic and nonesthetic zones is provided Furthermore, proto-cols for ridge preservation in the absence of buccal/lingual plates are included as well as an introduction to the concept and clinical indication for “socket shield” therapy

Chapter 4 covers the topic of alveolar ridge augmentation

Specific indications and a description of patient selection criteria, step-by-step surgical procedures, and aspects of postoperative treatment are presented This chapter also includes background information on guided bone regener-ation, intraoral bone harvesting techniques, horizontal and vertical alveolar ridge augmentation procedures in maxil-lary/mandibular posterior and anterior regions, ridge split techniques, and vestibuloplasty The numerous complica-tions faced during any of the above-mentioned procedures are also discussed with solutions to such encounters

Chapter 5 focuses on sinus grafting First, the history of sinus grafting is presented with an overview of anatomical considerations Clinical and radiographic assessment is then considered with detailed discussion of the lateral window versus crestal protocol utilized for specific clinical indica-tions Emphasis in this chapter includes instrumentation for sinus grafting, incision design and flap management, graft selection and placement, the use of osseodensification tech-nology, as well as protocols for sinus membrane repair Both one- and two-stage protocols are discussed with cases shown for single-tooth, multiple-tooth, and fully edentulous arches

The final section of this chapter covers numerous potential complications faced during sinus grafting and their resolution

Lastly, chapter 6 covers full-arch reconstruction utilizing

conventional conversion protocols and newer fully guided

immediate-reconstruction protocols in a detailed

step-by-step manner utilizing the nSequence patented technology

My hope is that through the numerous cases presented

throughout this textbook, clinicians will be better able to

implement evidence-based clinical decisions that will lead

to predictable bone augmentation results and long-term

success We live in an age where information can be obtained

through social media at an ever-increasing speed Clinicians

are now free to post cases directly to social media following

surgery and obtain nearly live feedback on their work This

provides the clinician and reader with direct responses to

their surgical work; however, with the number of new

tech-niques and protocols being utilized and promoted online, it

remains difficult to assess and scientifically critique many of these newer protocols without proper long-term follow-up

Having practiced implant dentistry for more than 35 years,

I consider follow-up times of 1 year, 5 years, and 10 years to

be immeasurably important This book focuses exclusively

on the protocols that have been developed over numerous years with established long-term follow-ups to provide the reader with a set of surgical guidelines and principles with predictable long-term documented outcomes Furthermore,

an online video series available at www.pikosonline.com will supplement the book to further guide the clinician with surgical demonstrations provided within our online teaching library I sincerely hope that these videos in conjunction with the content of this book will provide an enjoyable learning experience, and I look forward to your future feedback

Acknowledgments

Although the acknowledgments are typically found in the

first pages of a book, they are usually the last piece to be

written And for good reason, as they allow the author to

reflect on those individuals who have contributed in one

way or another to its completion

For the development and production of this book, I owe

a deep sense of gratitude to the following people:

My incredible and selfless wife Diane, daughter Lindsey, and

son Tony for sacrificing our time together and for their

uncon-ditional love, support, and encouragement during all these years

My beloved mother Mary, and to the joyous memory

of my father Anthony, both of whom provided for me a

sound spiritual-based and loving environment with solid

core values from which to grow

The many teachers and mentors who have so impacted

my life and career, with special thanks to Carl Misch, Tom

Golec, Leonard Linkow, Hilt Tatum, P.D Miller, and Pat Allen

My Institute team—Alison Thiede, Kali Kampmann,

Mark Robinson, and Roger Hemond—for their

uncon-ditional commitment to excellence

My fellow clinicians and staff whom I have had the honor

of working with during my 36 years of private practice

The thousands of clinicians whom I have had the honor and privilege to meet both at my Institute and from main podium lectures throughout the world

The thousands of patients for entrusting me with their implant surgical care over all these years

Rick Miron, an awesome, highly intelligent, yet so humble colleague and friend without whose help this book would definitely not be possible

The entire team at Quintessence Publishing, including Leah Huffman (Senior Editor), Angelina Schmelter (Digital

& Print Production Specialist), Bryn Grisham (Director of Book Publications), and especially William Hartman (Execu-tive Vice President & Director) This book certainly has been improved many times over, and I thank each of you for your dedication, patience, and helpfulness leading to its completion

And Almighty God for blessing me with a profession that

I have had such great passion for, and more importantly for giving me the skill sets necessary to help transform people’s lives on a daily basis

I nstrumentatIon

for a lveolar r Idge

a ugmentatIon and

s Inus g raftIng

Taugmentation and sinus grafting has played a pivotal

role in modern regenerative dentistry Many tools such as cone beam computed tomography (CBCT) have greatly improved the clinician’s ability to diagnose and

treatment plan cases with optimal accuracy and predictability

in implant dentistry Other devices such as Osstell’s implant

stability quotient (ISQ) tool can be utilized to accurately

monitor implant stability over time Furthermore, radio-

frequency, Piezosurgery (Mectron), and osseodensification

(OD) burs have greatly improved surgical outcomes for the

clinician This chapter provides an overview of the various

instruments most frequently utilized by the author on a daily

basis within his private practice and institute Furthermore, a

brief overview of their technologies and uses in alveolar ridge

augmentation and sinus grafting is presented

CBCT

In the last decade, the use of 3D CBCT has dramatically

intro-duced (mainly in implantology), its use was limited to a small

number of specialists, due primarily to its limited indications,

high costs, and elevated dose of radiation In the late 1990s,

a new technology using a “cone beam” and a

reciprocat-ing detector, which rotates around the patient 360 degrees,

entered the dental implant field, making high-definition 3D

scans easily accessible to dentists and their patients

By 2005, I began utilizing CBCT technology in my own

private practice and teaching institution Because my

prac-tice has been limited to implant reconstruction for the past

25 years, I require ALL of my patients to have a CBCT scan,

as this 3D technology plays an integral role in overall

diag-nosis and treatment planning CBCT has seen widespread

use in all fields of dentistry, including implantology, oral

One of the major breakthroughs in CBCT technology

was the ability to use significantly smaller doses of

estab-lishment of sensitive radiographic techniques for assessing

Fig 1-1 (a) CBCT imaging

system (Carestream [CS]

9600) (b) Notice the

capa-bility to create 3D structions of bone and teeth with excellent resolution.

recon-b

a

dentoalveolar structures led to its more frequent use owing

to its higher safety standards Today, all patients within my practice requiring implant dentistry or bone augmenta-tion procedures must have a CBCT image taken prior to implant therapy, bone augmentation, or sinus augmentation

in order to fully characterize anatomical malities and diagnose potential pathology Furthermore, the use of CBCT for postgraft evaluation prior to implant placement has become routine

features/abnor-Carestream Dental provides a high-quality CBCT system

system include the ability to perform all necessary

exam-inations with one system (CS 9600 family) Image

reso-lution can reach up to 75 μm (sizes up to 16 × 17 cm),

ideal for a wide range of applications from implantology to

oral surgery, orthodontics, and endodontics (Fig 1-2) These

features will only further improve over time Low-dose

imaging modes are also possible with 3D image quality,

utilizing lower doses of radiation when compared to

tradi-tional panoramic radiographs Box 1-1 provides a list of

relevant features of the system

Hand Instruments

Hand instruments are widely utilized within any dental office,

with various companies now promoting sales of their

indi-vidual items Salvin Dental has been recognized as one of

the leaders in the field, and together we have codeveloped many specific trays for implant surgery (Fig 1-3), soft tissue grafting (Fig 1-4), block grafting (Fig 1-5), and sinus grafting (Fig 1-6) Each kit contains various useful instruments that have assisted our team in surgery

Nevertheless, each instrument must be chosen according

to the treating surgeon’s preference For example, one ment used specifically when dealing with full-arch cases is the right-angle torque wrench (Salvin AccessTorq Right Angle Variable Torque Driver), with adjustable Ncm features from 10 to 35 Ncm (Fig 1-7) This instrument is valuable for hard-to-reach areas Another tool frequently utilized in large bone augmentation procedures is the Pro-fix Preci-

self-drilling membrane fixation screws, self-drilling ing screws, and self-tapping bone fixation screws (Fig 1-8), shown in a number of bone augmentation procedures in chapter 4

tent-Fig 1-2 CS 9600 used to image a

full-arch case (a) Notice that a single scan

can be useful to identify pathologies with much greater accuracy than with

a conventional 2D radiograph (b)

Furthermore, the beauty of the CS

9600 is its capability to combine head facial features into the program for better treatment planning.

full-a

b

Panoramic modality

Sensor technology: CMOS Image field (mm): 6.4×140 (for adult patient), 6.4×120 (for child patient), 120×140 (for sinus one-shot examination) Magnification: 1.28

Exposure time: 0.5–13 seconds

Cephalometric modality

Sensor technology: CCD Exposure time: 0.1–3.2 seconds Radiologic examination options: Lateral, frontal

AP or PA, oblique, submentovertex, carpus Acquisition format size (cm): 18×18, 18×24, 24×24, 24×30, 30×30

X-ray generator and other specifications

Tube voltage: 60–90 kV Tube current: 2–15 mA Frequency: 140 kHz Tube focal spot: 0.3 or 0.7 mm

Fig 1-3 The Pikos implant surgical kit: Quinn Type Periosteal Elevator, 2

Minnesota Retractors, Jacobson Long Castroviejo Needle Holder, Seldin

Retractor, Dean Scissor, Siegel Round Scalpel Handle, Adson 1×2 Tissue

Forceps, Adson Serrated Tissue Forceps, Gerald Micro Surgical Tissue

Forceps–Serrated, Gerald Micro Surgical Tissue Forceps–1×2, Kelly Curved

Hemostat, Crile-Wood Needle Holder, Castroviejo Micro Scissors–Curved,

Periotome Straight, Molt Mouth Gag, Weider Tongue Retractor, Castroviejo

Caliper, Friedman Rongeur, 10×6 Instrument Cassette, 10×6 Instrument

Deep Cassette (Courtesy of Salvin Dental.)

Fig 1-4 The Pikos soft tissue grafting instrumentation kit: UNC Perio Probe, Frazier 3mm Surgical Aspirator, Siegel Round Scalpel Handle, Handle For Bendable Micro Blades, Bendable Micro Blades–Nordland #69 (Box of 6), Quinn Type Periosteal Elevator, Adson 1×2 Tissue Forceps, Adson Serrated Tissue Forceps, Gerald Micro Surgical Tissue Forceps–Serrated, Gerald Micro Surgical Tissue Forceps–1×2, Rhodes Chisel, Gracey 11/12 Curette, Kelly Curved Hemostat, Corn Plier, Crile-Wood Needle Holder, Dean Scissor, Micro Needle Holder, Castroviejo Micro Scissors, 10×6 Instrument Cassette, 10×6 Instrument Deep Cassette (Courtesy of Salvin Dental.)

Box 1-1 Features of the CS 9600 system

CMOS, complementary metal oxide semiconductor;

CCD, charge-coupled device; AP, anteroposterior; PA, posteroanterior.

Fig 1-5 The Pikos bone block grafting instrumentation kit: Tatum “D”

Shaped Spreader #3, Tatum “D” Shaped Spreader #4, 6mm Cottle Curved

Chisel, 6mm Sheehan Straight Chisel, Pikos Ramus Retractor, Quinn Type

Periosteal Elevator, Siegel Round Scalpel Handle, Castroviejo Caliper–Short,

Pikos Block Grafting Bur Kit, 1.5mm Wire Passing Bur, Stainless Steel

Orga-nizing Cassette (Courtesy of Salvin Dental.)

Fig 1-6 The Pikos sinus elevation kit: Set of 5 Sinus Curettes (#1, #5, Freer, Pikos #7, Pikos #8), Graft Material Packer–Double Ended, Bone Spoon / 4mm Graft Packer Combination, Stainless Steel Organizing Cassette (Cour- tesy of Salvin Dental.)

Fig 1-9 The Osstell IDx is a fast, noninvasive, and easy-to- use system to determine implant stability and assess osseointegration It provides accurate, consistent, and objec- tive information needed to assess when implants may be loaded (Courtesy of BioHori- zons.) Note: I utilize Osstell

technology primarily in delayed loading implant cases This gives me a frame of reference at the time of implant placement compared

to the time of loading My goal

is for an ISQ value of 65 or

Fig 1-7 Right-angle torque

wrench with adjustable Ncm

features from 10 to 35 Ncm

(Courtesy of Salvin Dental.)

Fig 1-8 The Pro-fix Precision Fixation System is manufac- tured to precise tolerances to ensure easy pickup of screws, stable transfer to the surgical site, and quick engagement in cortical bone (Courtesy of Osteogenics.)

Osstell IDx

The value of the Osstell system is that it helps clinicians

objectively determine implant stability and assess the

reviewed research articles supporting its use It is a fast, easy,

and reliable way to provide accurate and objective

informa-tion needed to proceed with implant loading My cases are

routinely tested for ISQ values to assess implant stability ISQ

values may potentially reduce treatment time, better manage

risk, and offer an ability to better communicate findings

with patients The Osstell system allows for the quick and

easy identification of which implants are ready for loading

and which need additional healing time in an objective way,

Radiosurgery Device

A radiosurgical energy source (Fig 1-10) delivers advanced

radiowave technology and provides outstanding surgical

control, precision, and versatility.15,16 Unlike lasers, the high

frequency of the 4-MHz Surgitron Dual 120 surgical device

minimizes heat dissipation, and thus cellular alteration, while

cutting and coagulating soft tissues Approximately 50 watts of

power is utilized with the ability to micro-coagulate pinpoint

locations This favors minimal charring or tissue necrosis and

is ideal for the oral maxillofacial region with critical anatomy

Advantages include reduced postoperative discomfort and

minimal scar formation Typical radiosurgery systems come

with the following four waveforms

Fully rectified filtered waveform

• Used for performing deep surgical incisions

• Waveform mimics the cut of a scalpel blade with only

minimal coagulation

produces the most delicate of incisions

Fig 1-10 The Surgitron Dual 120 surgical device (Ellman Interna- tional), utilized to cauterize blood vessels during surgery.

Fig 1-11 Use of the Ellman Surgitron device to cauterize a blood vessel following flap elevation.

Fully rectified waveform

• Produces an incision with concurrent coagulation

• Allows increased visibility due to enhanced coagulation

Partially rectified waveform

• Strictly a coagulating waveform

• Used in areas of bleeding or oozing

Bipolar radiosurgery

• Bipolar electrodes coupled with a radiosurgical wave form

• Higher radiofrequency of 4 MHz versus bipolar surgical signal of 1.8 MHz

electro-• Research has shown that high-frequency radiosurgery produces less tissue alteration and lateral heat to the surrounding tissue than does the low-frequency elec-trosurgical signal (Fig 1-11)

• The bipolar componentry of radiosurgery is a must for clinicians involved with implant surgery This is true because it allows for cauterization in the presence of body fluids (blood and saliva)

Piezosurgery Device

One of the most widely utilized new tools in implant

dentistry over the past decade has been the Piezosurgery

device (Fig 1-12) More specifically, Mectron’s dual-wave

technology has been frequently cited owing to its patented

Work pioneered by Professor Tomaso Vercellotti in Italy

demonstrated that a primary wave between 24 and 36 kHz

modulated by a secondary low-frequency wave from 30 to

60 Hz could be utilized to efficiently maximize bone cutting

Piezo-surgery handpiece is therefore a high-frequency electrical

impulse unit with micrometric movement of approximately

80 µm in the horizontal amplitude and 5 µm in the vertical

direction (Fig 1-13) The device comes with more than 100 different tips characterized by their ability to seamlessly and efficiently cut bone all while being capable of differentiat-ing between hard and soft tissues These features have been demonstrated to decrease the risk of damage to important anatomical structures such as nerves and membranes Piezo-surgery has been shown to clinically lower the rate of sinus membrane perforations and has also been frequently utilized during ridge split procedures and harvesting of bone blocks (Fig 1-14) The author utilizes piezosurgical technology on

a daily basis for a variety of bone-based surgical procedures that include but are not limited to the following: sinus graft-ing, ridge splitting, harvesting autogenous bone blocks, and recipient site preparation for bone grafts

Fig 1-12 Mectron’s Piezosurgery device Its patented technology allows for the precise cutting of alveolar bone while minimizing the risk of soft tissue injury.

Fig 1-13 The Piezosurgery handpiece is a high-frequency electrical impulse from the console to the ceramic disks The electricity induces mechanical deformations of the ceramic disks, which are transferred to the insert to generate a micrometric cutting action

The micrometric movement is approximately

80 µm in the horizontal amplitude and 5 µm

in the vertical direction.

Insert tip Concentrator Resonator

Mechanical dipole

Generator Piezo-ceramic

rings

Versah Burs

The use of OD burs has also substantially improved our

ability to obtain primary stability in low-density bone (Fig

1-15) The biomechanical stability of implants has typically

been dependent on several factors, including implant macro

and micro design as well as the quality and quantity of

to increase implant primary stability over the years:

• Drilling protocol: underpreparation of osteotomy

• Implant type: macrotexture and microtexture

• Longer implants providing greater bone-to-implant

contact (BIC)

• Techniques for osseocondensation of bone

Bone has long been considered an ideal tissue in the body because it is flexible, changing shape via deformation (without necessarily breaking/cracking), can withstand and widen during compression, and is able to lengthen during tension.23

Bone is typically prepared prior to implant placement utilizing standard drill burs Because fresh, hydrated trabecu-lar bone is a ductile material, it has a good capacity for plastic deformation Osseodensification is essentially a burnishing process that redistributes bone material on the bony surface through plastic deformation The counterclockwise rotation

of OD burs causes the lands of the bur to slide across the surface of the bone via low plastic deformation; these burs are purposefully designed with a compressive force less than the ultimate strength of bone As a result, OD burs have

Fig 1-14 (a and b) Use of a Piezosurgery device to harvest a symphysis bone block.

Fig 1-15 Group of 12 OD burs (Versah) utilized during crestal sinus augmentation procedures to compact bone.

b a

several reported advantages First, they create live, real-time

haptic feedback that informs the surgeon if more or less

force is needed, allowing the surgeon to make

instanta-neous adjustments to the advancing force depending on the

given bone density These burs rotate in a counterclockwise

direction and do not “cut” as expected with conventional

burs They therefore densify bone (D3, D4) by rotating in

the noncutting direction (counterclockwise at 800–1,200

rotations per minute) It has been recommended by the

manufacturer that copious amounts of irrigation fluid be

used during this procedure to provide lubrication between

the bur and bone surfaces and to eliminate overheating

OD burs have been shown to produce compression waves,

where a large negative rake applies outward pressure that

laterally compresses bone during the continuously rotating and concurrently advancing bur This facilitates “compaction autografting” or “osseodensification.” During this process, bone debris is redistributed up the flutes and is pressed into

auto-grafting supplements the basic bone compression, and the condensation effect acts to further densify the inner walls

of the osteotomy.25 Trisi et al were one of the first to study

OD burs increased the percentage of bone density/BIC values around dental implants inserted in low-density bone

(Fig 1-17) These burs are highlighted primarily in chapter

5 under sinus augmentation procedures

Fig 1-16 Results from a preclinical study demonstrating the

capability of OD to densify bone when utilized correctly (a)

Surface view of 5.8-mm standard drilling (SD), extraction

drill-ing (ED), and OD osteotomies (b and c) Microcomputed

tomography midsection and cross section Notice the layer of dense bone produced on the outer surface of the OD group

(Reprinted with permission from Huwais and Meyer 24 )

Fig 1-17 Clinical use of OD burs during a sinus augmentation dure with minimal residual bone height.

proce-a

b

c

The use of novel instruments has facilitated the ability of

the clinician to perform more predictable and accurate bone

augmentation and sinus grafting Today, the use of CBCT has

been shown to markedly improve diagnostics and treatment

planning in implant dentistry, and it is something I consider

a necessity and standard for the field In addition to hand

instruments that have been utilized and further refined over

the years, new instrumentation has become available This

includes but is not limited to radiosurgery, Piezosurgery,

Osstell ISQ implant stability devices, and OD burs, all of

which can be utilized on a routine basis for alveolar ridge

augmentation and sinus grafting in implant dentistry While

their introduction was brief in this chapter, their use is

further highlighted in the clinical chapters of this textbook

Furthermore, as the field continues to advance rapidly,

new devices will certainly be brought to market in the

coming years For a current list of the tools and instruments

utilized for alveolar ridge augmentation in my practice and

guidelines for their use, a detailed and up-to-date description

is provided at www.pikosonline.com

References

1 Scarfe WC, Angelopoulos C (eds) Maxillofacial Cone Beam Computed

Tomography: Principles, Techniques and Clinical Applications New York: Springer, 2018.

2 Benavides E, Rios HF, Ganz SD, et al Use of cone beam computed

tomography in implant dentistry: The International Congress of Oral Implantologists consensus report Implant Dent 2012;21:78–86.

3 Ludlow J, Timothy R, Walker C, et al Effective dose of dental CBCT—A

meta analysis of published data and additional data for nine CBCT units

Dentomaxillofac Radiol 2014;44:20140197.

4 Urban I, Jovanovic SA, Buser D, Bornstein MM Partial lateralization of

the nasopalatine nerve at the incisive foramen for ridge augmentation in the anterior maxilla prior to placement of dental implants: A retrospec- tive case series evaluating self-reported data and neurosensory testing

Int J Periodontics Restorative Dent 2015;35:169–177.

5 Chan HL, Benavides E, Tsai CY, Wang HL A titanium mesh and

partic-ulate allograft for vertical ridge augmentation in the posterior mandible:

A pilot study Int J Periodontics Restorative Dent 2015;35:515–522.

6 Herrero-Climent M, Santos-García R, Jaramillo-Santos R, et al

Assessment of Osstell ISQ’s reliability for implant stability ment: A cross-sectional clinical study Med Oral Patol Oral Cir Bucal 2013;18:e877–e882.

measure-7 Shin SY, Shin SI, Kye SB, et al The effects of defect type and depth, and measurement direction on the implant stability quotient (ISQ) value J Oral Implantol 2015;41:652–656.

8 Yoon HG, Heo SJ, Koak JY, Kim SK, Lee SY Effect of bone quality and implant surgical technique on implant stability quotient (ISQ) value J Adv Prosthodont 2011;3:10–15.

9 Baldi D, Lombardi T, Colombo J, et al Correlation between insertion torque and implant stability quotient in tapered implants with knife- edge thread design Biomed Res Int 2018;2018:7201093.

10 Bruno V, Berti C, Barausse C, et al Clinical relevance of bone density values from CT related to dental implant stability: A retrospective study

Biomed Res Int 2018;2018:6758245.

11 Buyukguclu G, Ozkurt-Kayahan Z, Kazazoglu E Reliability of the Osstell implant stability quotient and Penguin resonance frequency analysis to evaluate implant stability Implant Dent 2018;27:429–433.

12 Nakashima D, Ishii K, Matsumoto M, Nakamura M, Nagura T A study

on the use of the Osstell apparatus to evaluate pedicle screw stability: An in-vitro study using micro-CT PLoS One 2018;13:e0199362.

13 Balleri P, Cozzolino A, Ghelli L, Momicchioli G, Varriale A Stability measurements of osseointegrated implants using Osstell in partially edentulous jaws after 1 year of loading: A pilot study Clin Implant Dent Relat Res 2002;4:128–132.

14 Sim CP, Lang NP Factors influencing resonance frequency analysis assessed by Osstell™ mentor during implant tissue integration: I In- strument positioning, bone structure, implant length Clin Oral Implants Res 2010;21:598–604.

15 Sherman JA Oral Radiosurgery: An Illustrated Clinical Guide, ed 2

London: Martin Dunitz, 1997.

16 Sharma S, Gambhir R, Singh S, Singh G, Sharma V Radiosurgery in dentistry: A brief review Ann Dent Res 2014;2:8–21.

17 Vercellotti T, Nevins ML, Kim DM, et al Osseous response following resective therapy with Piezosurgery Int J Periodontics Restorative Dent 2005;25:543–549.

18 Vercellotti T, De Paoli S, Nevins M.The piezoelectric bony window osteotomy and sinus membrane elevation: Introduction of a new tech- nique for simplification of the sinus augmentation procedure Int J Periodontics Restorative Dent 2001;21:561–567.

19 Vercellotti T Piezoelectric surgery in implantology: A case report—A new piezoelectric ridge expansion technique Int J Periodontics Re- storative Dent 2000;20:358–365.

20 Vercellotti T, Nevins ML, Kim DM, et al Osseous response following resective therapy with piezosurgery Int J Periodontics Restorative Dent 2005;25:543–549.

21 Vercellotti T, Pollack AS A new bone surgery device: Sinus grafting and periodontal surgery Compend Contin Educ Dent 2006;27:319–325.

22 Meyer U, Vollmer D, Runte C, Bourauel C, Joos U Bone loading tern around implants in average and atrophic edentulous maxillae: A finite-element analysis J Craniomaxillofac Surg 2001;29:100–105.

pat-23 Seeman E Bone quality: The material and structural basis of bone strength J Bone Miner Metab 2008;26:1–8.

24 Huwais S, Meyer EG A novel osseous densification approach in implant osteotomy preparation to increase biomechanical primary stability, bone mineral density, and bone-to-implant contact Int J Oral Maxillofac Implants 2017;32:27–36.

25 Trisi P, Berardini M, Falco A, Podaliri Vulpiani M New osseodensification implant site preparation method to increase bone density in low-density bone: In vivo evaluation in sheep Implant Dent 2016;25:24–31.

M eMbranes ,

G raftinG M aterials , and G rowth

f actors

Tmodern regenerative dentistry While they were

once thought to act as passive structural als capable of filling bone voids, more recently,

materi-a number of regenermateri-ative materi-agents with biomateri-active properties

have been brought to market These materials act to

facil-itate bone regeneration and have vastly improved the ease

and predictability of bone augmentation procedures This

chapter provides an overview of the various biomaterials

used for bone regeneration and discusses the regenerative

properties of commercially available barrier membranes,

bone grafting materials, and growth factors Each

bioma-terial is discussed in the context of its biologic properties,

and clinical indications are provided with respect to their

application in alveolar bone augmentation procedures

Barrier Membranes

Guided tissue and bone regeneration were first introduced

to the dental field over 20 years ago Interestingly, in the

early 1970s, it was not common knowledge that periodontal

ligament cells were responsible for the healing capabilities

the mid-1980s, it was widely accepted and believed that

progenitor cells for all tissues found in the periodontium

late 1980s, and convincingly at the beginning of the 1990s

following a series of experiments in monkeys, that

conclu-sive evidence supported the notion that progenitor cells

in the periodontium were derived from the periodontal

ligament tissue.3–5

Based on these results, it was hypothesized that a higher

regenerative potential might be obtained if cells derived

from the periodontal ligament and alveolar bone were

exclusively allowed to repopulate the root surface away

from the faster-growing epithelium and gingival

attempted in the field of periodontology under the

work-ing name guided tissue regeneration (GTR) and was aimed at

Fig 2-1 The first barrier membranes utilized in dentistry for GTR were lose acetate laboratory filter or ePTFE membranes dating back to the 1980s

cellu-Demonstrated here are more modern smooth (a) and textured (b) Cytoflex

Tefguard (Unicare) ePTFE membranes.

selectively guiding tissue regeneration around tissues in the periodontium The first barrier membranes utilized were cellulose acetate laboratory filter or expanded polytetraflu-

months of healing, it was concluded by histologic evaluation that the test root surfaces protected from epithelial down-growth by membranes exhibited considerably more new

confirmed the hypothesis that by selectively controlling the proliferation of cells in the periodontium, and by prevent-ing contact with the epithelial and connective tissues, the space-maintaining capability of the membrane would allow for increased regeneration of underlying tissues

Subsequently, the basic principles of guided bone eration (GBR) were introduced by providing the cells from bone tissues with the necessary space intended for bone regeneration away from the surrounding connective tissue

clinical studies have since demonstrated that by applying the concepts of GBR, an increase in bone regeneration may be

tissue regeneration have been developed, GBR has remained one of the most predictable solutions to bone defect healing

This section presents the advantages and disadvantages of various membranes for GBR procedures, discussing their mechanical properties and degradation rates

Requirements of barrier membranes

for GBR

While the first successful barrier membrane was a cellulose

range of new membranes have been designed with better

biocompatibility for various clinical applications Each of

these membrane classes possesses distinct advantages and

disadvantages As a medical application in dentistry, barrier

membranes should fulfill some fundamental requirements

(Fig 2-2):

• Biocompatibility: The interaction between membranes and

host tissue should not induce a foreign body response

• Space-making: The ability to maintain a space for cells

from surrounding bone tissue for a specific time duration

• Cell occlusivity: Prevents fibrous tissue that delays bone

formation from invading the defect site

• Mechanical strength: Proper physical properties to allow

and protect the healing process, including protection of

the underlying blood clot

• Degradability: Adequate degradation time matching the

regeneration rate of bone tissue, avoiding a secondary

surgical procedure to remove the membrane

Several commercially available membranes are classified according to their material properties in Table 2-1 and high-lighted below.13–38

Nonresorbable membranes

Nonresorbable membranes include expanded (ePTFE), high-density (dPTFE), and titanium-reinforced (PTFE-TR)

animal studies involving various defect configurations as well

as histologic data from both animal and human studies have

Nonresorbable membranes have several advantages and disadvantages Their main advantage is their superior rigidity over resorbable collagen-based membranes Their main disadvantage is the requirement for a second surgical

which bears the potential for re-injuring and/or mising the obtained regenerated tissue However, clinical indications presented later in this textbook demonstrate various applications where their use is pivotal because of

nonre-sorbable membranes are effectively biocompatible and offer the added ability to maintain sufficient space in the membrane for longer periods when compared to resorbable membranes They have a more predictable profile during the healing process because of their better mechanical strength, and their handling has been made easier over the years.42

PTFE membranes

PTFE membranes were first introduced to dentistry in 1984

Prior to that, these membranes were utilized clinically for lar applications in general medicine as a vascular graft mate-rial for hernia repair.43,44 Each side of the porous structure of

micro-structure collar 1 mm thick and with 90% porosity retards the growth of the epithelium during the early wound healing phase; on the other side, a 0.15-mm-thick and 30% porous membrane provides space for new bone growth and acts to prevent fibrous ingrowth The average healing period after in vivo implantation is approximately 3 to 9 months depending

on the clinical application

The advantages of dPTFE membranes (Fig 2-3), which feature 0.2-µm pores, are that they do not require primary closure and have been widely utilized for ridge preservation

the conventional ePTFE, dPTFE membranes demonstrate lower rates of infection and are easily removed dPTFE membranes may also be reinforced with titanium (Fig 2-5)

These membranes are excellent choices for large GBR

Fig 2-2 The ideal barrier membrane for GBR procedures needs to fulfill

the following criteria: biocompatibility, space-making ability, cell occlusivity

to prevent epithelial tissue downgrowth, ideal mechanical strength, and

optimal degradation properties.

Space-making

Mechanical strength occlusivity Cell

Degradability timeline Compatibility

Table 2-1 Classification of different membranes in GBR

Non-

resorbable

membranes

GORE-TEX (W L Gore) ePTFE Good space maintainer; easy to handle Longest clinical experience 13,14

GORE-TEX-TI (W L Gore) ePTFE-TR Most stable space maintainer; filler material unnecessary Titanium should not be ex-posed; commonly used

in ridge augmentation 15

High-density GORE-TEX

Cytoplast (Osteogenics) dPTFE 0.3-μm pores Primary closure unnecessary 17

TefGen-FD (Lifecore Biomedical) dPTFE 0.2- to 0.3-μm pores Easy to detach18Nonresorbable ACE

(ACE Surgical Supply) dPTFE < 0.2-μm pores; 0.2 mm thick Limited cell proliferation19Titanium Augmentation

Micro Mesh (ACE Surgical Supply) Titanium mesh 1,700-µm pores; 0.1 mm thick Ideal long-term survival rate

20

Tocksystem Mesh (Tocksystem) Titanium mesh 0.1- to 6.5-µm pore; 0.1 mm thick Minimal resorption and inflammation 21

Frios BoneShields (Dentsply Friadent) Titanium mesh 0.03-mm pores; 0.1 mm thick Sufficient bone to regenerate21M-TAM (Stryker Leibinger) Titanium mesh 1,700-µm pores; 0.1 to 0.3 mm thick Excellent tissue compatibility 22

Synthetic

resorbable

membranes

OsseoQuest (W L Gore) Hydrolyzable polyester Resorption: 16–24 weeks Good tissue integration 23

Biofix (Bioscience) Polyglycolic acid Resorption: 24–48 weeks Good space-making ability 24

Vicryl (Ethicon) Polyglactin 910, polyglycolic-

polylactic acid 9:1

Well adaptable; resorption:

4–12 weeks Woven membrane; four prefabricated shapes 25

Atrisorb (Tolmar) Poly-DL-lactide and solvent Resorption: 36–48 weeks; inter-esting resorptive characteristics Custom-fabricated membrane “barrier kit”26EpiGuide (Kensey Nash) Poly-DL-lactic acid Three-layer membrane; resorption: 6–12 weeks Self-supporting; support- developed blood clot27

Resolut (W L Gore) Poly(DL-lactide- co-glycolide) Resorption: 10 weeks; good space maintainer Good tissue integration; separate suture material28VIVOSORB (Polyganics) Poly(DL-lactide- ε-caprolactone) Anti-adhesive barrier; up to 8 weeks’ mechanical

properties Acts as a nerve guide

Abundant growth factors and proteins mediate cell behav- iors; different formulations for various usages; total resorption

Enhances osseointegration and initial implant stability;

promotes new bone formation;

encourages soft tissue ery 30,31

recov-Bio-Gide (Geistlich) Porcine 1 and 3 Resorption: 24 weeks; mechani-cal strength: 7.5 MPa Usually used in combination with filler materials32BioMend (Zimmer Biomet) Bovine 1 Resorption: 8 weeks; mechani-cal strength: 3.5–22.5 MPa Fibrous network; modulates cell activities33BioSorb membrane

(3M ESPE) Bovine 1 Resorption: 26–38 weeks Tissue integration34Neomem (Citagenix) Bovine 1 Double-layer product; resorption: 26–38 weeks Used in severe cases 35

OsseoGuard (BIOMET 3i) Bovine 1 Resorption: 24–32 weeks Improves the esthetics of the final prosthetics36OSSIX (OraPharma) Porcine 1 Resorption: 16–24 weeks Increases the woven bone 37

ePTFE-TR, titanium-reinforced ePTFE; dPTFE, dense PTFE; M-TAM, micro titanium augmentation mesh (Reprinted with permission from

Miron and Zhang 38 )

procedures because they provide additional mechanical

strength for the underlying particulate graft complex

Titanium mesh

Titanium-reinforced barrier membranes were introduced as

an option for GBR because they provide advanced

mechan-ical support that allows a larger space for bone and tissue

regrowth (Fig 2-6) The exceptional properties of rigidity, elasticity, stability, and plasticity make Ti mesh an ideal alter-

space maintenance and prevents contour collapse, its ity prevents mucosal compression, its stability prevents graft displacement, and its plasticity permits bending, contouring, and adaptation to any unique bony defect (Fig 2-7) The main disadvantage of Ti mesh membranes is increased exposure due to their stiffness Several reports have demonstrated up

elastic-to 50% membrane exposure during their use (see chapter 4) Various strategies, including the utilization of leukocyte platelet-rich fibrin (L-PRF), are discussed later in this chapter

as approaches to minimize membrane exposure

Resorbable membranes

The advantage of resorbable membranes (Fig 2-8) is that they permit a single-step procedure, thus alleviating patient discomfort and costs from a second procedure and avoiding the risk of additional morbidity and tissue damage These membranes are more favorable for minor GBR procedures that do not require extensive bone regeneration Further-more, they are also utilized extensively during sinus elevation procedures to repair sinus membrane perforations as well as

Fig 2-3 (a and b) A dPTFE

membrane (Cytoplast).

Fig 2-4 Use of a dPTFE membrane for socket grafting. Fig 2-5 A dPTFE membrane reinforced with titanium (Cytoplast Titanium-

Reinforced) for improved mechanical strength in single-tooth cases with a facial plate.

Fig 2-6 Titanium mesh

to close lateral windows (Fig 2-9) The main disadvantage

of resorbable membranes are their varied and sometimes

unpredictable resorption rates, which directly affect bone

as their resorption times is presented in Table 2-1

Fig 2-8 (a and b) Type 1 crosslinked bovine collagen membrane (Mem-Lok Pliable, BioHorizons) The prime advantage of collagen membranes is their

superior biocompatibility.

Fig 2-7 (a and b) Titanium meshes are adapted according to the defect morphology Typically two 5-mm Pro-fix screws (Osteogenics) are utilized for

both facial and lingual fixation

Fig 2-9 Type 1 crosslinked bovine collagen membrane (Mem-Lok) utilized

to cover a lateral window during a sinus augmentation procedure.

Synthetic resorbable membranes

A series of resorbable membranes mainly consisting of

poly-esters—eg, polyglycolic acid (PGA), polylactic acid (PLA),

and poly-ε-caprolactone (PCL)—and their copolymers are

or polylactide, are derived from a variety of origins and can

be made in large quantities with a wide spectrum,

offer-ing different physical, chemical, and mechanical properties

Interestingly, the resorption of various membranes occurs

Tatakis et al demonstrated that a large majority of collagen

membranes are resorbed by enzymatic activity of

infiltrat-ing macrophages and polymorphonuclear leukocytes, while

polymers are typically degraded through hydrolysis, and the

degradation products are metabolized through the citric acid

cycle For these reasons, synthetic resorbable membranes generally cause a higher inflammatory response, and their use has not been widespread in alveolar bone reconstruc-tion procedures

Membranes based on natural materials

The highest number of reported clinical studies involves the use of biodegradable resorbable membranes from natu-ral collagen (see Table 2-1) Membranes based on natural collagen are typically derived from human skin, bovine achilles tendon, or porcine skin and can be characterized

by their excellent cell affinity and biocompatibility.48,49 The main drawbacks of these membranes are their potential for losing their space-maintenance ability under physio-logic conditions, higher cost, and potential introduction of

Fig 2-10 SEM analysis of a collagen barrier membrane at three magnifications (a and b) Membrane surface reveals many collagen fibrils that are

inter-twined with one another with various diameters and directions (original magnification ×50 and ×200, respectively) (c) High-resolution SEM demonstrating

collagen fibrils ranging in diameter from 1 to 5 μm (original magnification ×1,600) (d) Cross-sectional view of a collagen barrier membrane at approximately

300 μm (original magnification ×100) (Reprinted with permission from Miron et al 51 )

a

c

b

d

a foreign biomaterial when applying animal-derived

studied membrane available on the market and offer the

advantages of high biocompatibility and biodegradability,

eliminating the need for a second surgical procedure Figure

2-10 shows scanning electron micrographs (SEMs) of a

natural non-crosslinked collagen membrane commonly used

crosslinked collagen membrane and a standard membrane

Conclusion

Barrier membranes are pivotal biomaterials for bone

augmentation procedures and are greatly utilized

through-out the clinical chapters of this textbook dPTFE membranes

have better mechanical properties when compared to

resorb-able collagen membranes and have been further reinforced

with titanium more recently Similarly, Ti meshes have been

increasingly utilized over the years because of their excellent

combination of rigidity and stability, which enables them to

prevent flap collapse and ensure tension-free bone

regenera-tion Their drawback, however, is a higher rate of membrane

exposure Resorbable membranes are favored when a second

surgical procedure is not needed, preventing secondary

complications associated with membrane removal, including

additional patient morbidity and potential risk for

second-ary infection Collagen membranes are utilized in chapter 5

during sinus elevation procedures for sinus membrane repair

and also for lateral window closure Over the years, each

of these classes of barrier membranes has become

increas-ingly more biocompatible Ongoing research is presently

investigating the use of barrier membranes with a variety

of additional regenerative agents such as growth factors and

antibacterial agents The next generation of membranes is

expected to incorporate more functional biomolecules into

the design of current standards and is projected to more favorably promote the success of GBR therapies

Bone Grafting Materials

The use of bone grafting materials in implant dentistry and oral surgery has become so widespread over the past two decades that new products are rapidly brought to market year after year Each material and category of bone graft has its specific regenerative properties The most common classification of bone grafting materials includes the following (Fig 2-12):

• Autografts (same individual)

• Allografts (human cadaver bones)

• Xenografts (animal source)

• Alloplasts (synthetic source)This section focuses on the research and regenerative poten-tial of each of these classes of bone grafting materials

Originally bone grafting materials were developed to serve

as a passive, structural supporting network, with their main

advance-ments in tissue engineering and regenerative medicine have enhanced each of their regenerative capacities, as confirmed

by histologic analysis (Fig 2-13) Today many bone ing materials have specially designed surface topographies

graft-at both the micro- and nanoscales aimed to further guide new bone formation once implanted in situ (Fig 2-14)

Data from the United States has shown convincingly that allografts are by far the most utilized bone graft currently available on the market (Fig 2-15) Interestingly, only 15%

of augmentation procedures utilize autogenous bone, despite

it being the gold standard for bone grafting

Fig 2-11 SEM analysis of a dense crosslinked collagen membrane (Mem-Lok) versus a standard membrane (Bio-Gide).

CLASSIFICATION OF BONE GRAFTING MATERIALS

Allogeneic bone

Bone from the same species but another individual

Xenogeneic bone

Material of biologic origin but from another species

Alloplast

Material of synthetic origin

Freeze-dried bone allograft Material derived from corals Glass-ceramics

Demineralized freeze-dried bone allograft

Deproteinized bone allograft Material derived from wood Metals

Material derived from calcifying algae PolymersFree frozen bone from animal bonesMaterial derived Calcium phosphates

Fig 2-12 Classification of bone grafting materials including autografts, allografts, xenografts, and alloplasts.

Fig 2-13 (a to c) Core biopsies were harvested prior to implant placement and investigated for new bone formation

after grafting with freeze-dried bone allograft (FDBA, MinerOss [BioHorizons]) After 4 months of healing, the nonvital bone was only 5% of the bone mass.

Fig 2-14 (a to d) SEMs demonstrating the 3D shape and topography of bone grafting materials (Reprinted with permission from Miron and Zhang.38 )

• Can be immunogenic

• Can carry infection

DEMINERALIZED BONE ALLOGRAFT 16%

• Donor site morbidity

• Pain, cost, operative risk

• Limited volume available

XENOGRAFT 22%

• Can be immunogenic

• Can carry infection

Fig 2-15 Data regarding the proportional use of each class of bone grafting material in the United States in 2019 The largest percentage of regenerative

procedures are performed with allografts (37% mineralized, 16% demineralized), followed by xenografts (22%), autografts (15%), and synthetic grafts/bone

morphogenetic protein (5% each) (Reprinted with permission from Miron and Zhang 38 )

The global market for bone grafting materials has now

surpassed $2.5 billion dollars annually and is only expected

of the regenerative properties of each of these bone grafting

materials is necessary; more specifically, clinical guidelines

throughout this textbook are presented with rationales for

selecting each grafting material for specific clinical

indica-tions Considering the wide range of uses for bone grafting

materials, it should be expected that no single material can

fulfill the task of augmenting bone in every clinical situation

Furthermore, in many clinical instances, a combination of

two or more bone grafting materials is necessary to lead to

better and more predictable outcomes

Each grafting material needs to fulfill several properties

related to its use, including optimal biocompatibility, safety,

ideal surface characteristics, proper geometry and handling,

as well as good mechanical properties Nevertheless, bone

grafts are routinely characterized by their osteogenic, osteo-

inductive, and osteoconductive properties The ideal graft

should therefore (1) contain osteogenic progenitor cells

within the bone grafting scaffold capable of laying new

bone matrix, (2) demonstrate osteoinductive potential by

recruiting and inducing mesenchymal cells to differentiate

into mature bone-forming osteoblasts, and (3) provide an

osteoconductive scaffold that facilitates three-dimensional

tissue ingrowth.55

Consequently, the gold standard for bone grafting is

autogenous bone because it possesses these three important

new bone formation, limitations including extra

surgi-cal time and cost as well as limited supply and additional

patient morbidity have necessitated alternatives This section

discusses harvesting techniques for autogenous bone with

respect to cell survival content, currently utilized bone

allografts, the advantages of xenografts, and the current

limitations of synthetic alloplasts.56–60

Autogenous bone

Autogenous bone grafting involves the harvesting of bone

obtained from the same individual and collected either

as a bone block or in particulate form (Fig 2-16) Typical

harvesting sites in the oral cavity include the mandibular

symphysis, ramus buccal shelf, and tuberosity (Fig 2-17) The

main advantage of autogenous bone is that it incorporates

all three of the primary ideal characteristics of bone grafts

(ie, osteoconduction, osteoinduction, and osteogenesis)

Autogenous bone grafts are known to release a wide

vari-ety of growth factors, including bone morphogenetic

proteins (BMPs), platelet-derived growth factor (PDGF),

transforming growth factor β (TGF-β), and vascular thelial growth factor (VEGF), as well as to regulate bone

using autogenous bone alone have been well documented

gold standard due to their ability to more rapidly stimulate new bone formation when compared to all other classes of

Harvesting techniques: Block graft versus particles

Much research over the years has compared the use of block grafts versus particulate grafts Of critical importance to the success of any autograft procedure is the clinician’s abil-ity to successfully harvest bone with vital osteoprogenitor cells It has previously been demonstrated that autograft preparations may be compromised by mechanical harvesting techniques as well as the duration of time between harvest-

blocks were commonly utilized as a means to augment major bone deficiencies.68–73 Their advantages include the ability to locally harvest a sufficient supply within the oral cavity and their excellent biocompatibility within host tissues Disad-vantages include additional patient morbidity such as nerve

previously utilized with great frequency, more commonly autogenous bone is harvested in particulate form due to ease of use and excellent predictability

Harvesting of bone particles can be achieved locally via several methods These include collections of bone parti-cles with a bone mill or piezosurgical device, collection of bone dust with a suction device, as well as the use of various instruments for bone scraping (Fig 2-19) Several studies have now pointed to the fact that harvesting technique has a significant influence on the viability of bone cells within the autografts.55,61,76,77 Briefly, these studies demon-strated that autogenous bone chips harvested with a bone mill or a bone scraper revealed much greater (up to four times higher) cell viability and subsequent growth factor release when compared to bone particles harvested with

a piezosurgical or bone suction device (Fig 2-20) High- resolution SEMs further showed that greater protein content was observed on the surface of bone particles harvested with the use of a bone mill and bone scraper It has therefore been generally recommended to minimize harvesting techniques with extensive washing in order to prevent protein removal

Two devices routinely utilized for autogenous bone ing include the SafeScraper (Geistlich) as well as the rotary bone harvester (RBH) system developed by Dr Homayoun Zadeh These two devices simplify the harvesting of autoge-nous bone chips and may be more commonly utilized by

harvest-Fig 2-16 Autogenous bone can be collected via either (a) a bone block or (b) bone particles.

Fig 2-18 (a and b) Autogenous bone demonstrates faster new bone formation when compared to all other groups in a number of comparative studies

In a study of 12 minipigs, three standardized defects (9 × 5 mm) were grafted with particulate autograft, Bio-Oss (Geistlich), or β-tricalcium phosphate

(β-TCP) plus an ePTFE membrane The animals were sacrificed at 1, 2, 4, or 8 weeks after grafting, and a histomorphometric study was carried out At 2

weeks, the autograft had the greatest new bone formation (17%), followed by the β-TCP (6.3%) and Bio-Oss (5.6%) At 4 and 8 weeks, the autograft and

β-TCP were comparable (54.4% and 57.4%, respectively) and showed greater new bone formation than the Bio-Oss (41.6%) The autograft resulted in

faster bone regeneration initially and an increased osseous maturity at all observation periods (Reprinted with permission from Jensen et al 66 )

Fig 2-19 (a to f) Various commercially available autogenous bone collectors.

0

2 weeks 4 weeks 8 weeks

TCP TCP TCP Autograft Bio-Oss Autograft Bio-Oss Autograft Bio-Oss

Histomorphometric analysis

Soft tissue Graft Bone

Autograft

β-TCP

Bio-Oss

Autograft

clinicians interested in optimizing large GBR procedures

with additional supplementation with autografts

Allografts

Bone allografts involve the harvesting of bone from a human

cadaver and safely processing and decontaminating it They

are categorized into two main groups: (1) fresh-frozen bone

or FDBA and (2) demineralized FDBA (DFDBA).While

allografts have been the most widely utilized replacement

grafting material in North America, a number of

Euro-pean and Asian countries do not permit their use The main

advantage of allografts over other commercially available

bone substitute materials are their incorporation of osteo-

inductive growth factors Many studies have demonstrated

their effectiveness in promoting new bone formation across

a wide array of defect types.78–81 Allografts remain the ideal

replacement material for a number of regenerative

proce-dures utilized in dentistry, including extraction socket

heal-ing, sinus elevation procedures, GBR procedures, and other

adjunctive grafting procedures in implant dentistry

Biologic background of allografts

Because allografts are derived from human tissues,

ster-ilization procedures aim to maintain certain regenerative

proteins and growth factors within their matrix,

includ-ing osteoinductive factors such as BMPs With respect

to allografts, it is important to note that because bone is

obtained from human cadavers from the general population, variability in their content does exist Reports have shown that certain commercially available allografts are less osteo- inductive than others due to patient variability as well as

of the first to report that allografts taken from different lots of various bone banks demonstrated marked variability ascribed to patient donor age, method of preparation, and/

or sterilization protocols.83,84

Differences have also been reported between FDBA and DFDBA, and it is important that the treating clinician be aware of these important distinctions Generally speaking, DFDBA is demineralized with hydrochloric acids, which facilitates the access and release of a multitude of growth

osteoinductive potential of allografts Nevertheless, DFDBA fails in that it resorbs rather quickly, and for these reasons FDBA is more routinely utilized for the majority of augmen-tation procedures Furthermore, FDBA grafts are also more radiopaque and can be visualized better on radiographs when compared to radiolucent DFDBA grafts (due to their absence of mineralized components) The use of allografts is covered extensively throughout this book, MinerOss being the material utilized for the majority of cases MinerOss is

a mixture of corticocancellous bone that takes advantage

of the increased regenerative properties of cancellous bone and the strength of cortical bone; its particles range in size from 600 to 1,200 microns (Fig 2-21)

Fig 2-20 (a and b) Experimental analysis from various preclinical models has convincingly shown that autogenous bone chips

harvested with a bone mill or bone scraper demonstrate significantly more cell viability and release much higher amounts of

growth factors than do bone chips harvested with a piezosurgical or bone suction device The asterisk denotes a significant

difference (Reprinted with permission from Miron and Zhang 38 )

Mill Piezo Slurry Scraper

Mill Piezo Slurry Scraper

When xenografts were first commercialized over two

decades ago, it was relatively unknown to what extent bone

resorption would occur following their implantation Today,

xenografts are perhaps the most widely researched bone

grafting material in the dental field, with their use being

widespread internationally It is understood that the most

prominent advantage is their nonresorbable properties

Unlike allografts, which are prone to dimensional change

over time, xenografts maintain their volume Over the years,

a variety of procedures in dentistry have been adapted to take

advantage of these low–substitution rate materials These are

covered extensively throughout the book

The most widely utilized and well-documented

DBBM is a highly purified anorganic bone matrix mineral

ranging in size from 0.25 to 1 mm, trademarked under the

name Bio-Oss (Fig 2-22) The advantages of DBBM as a

bone grafting material include its documented safety and

mineral content, which is comparable to human bone with

nonresorbable characteristics Xenografts do not possess

any form of osteogenic or osteoinductive potential due to

their complete deproteinization process However, their

nonresorbable features make them attractive bone grafts in

a variety of clinical situations where the clinician may be

As such, DBBM particles have been utilized in a number

of clinical indications, including for contour augmentation

in implant dentistry (especially in the esthetic zone), sinus augmentation procedures, vertical augmentation procedures, and major bone reconstructive surgery where the clini-cian might fear potential resorption While it was originally thought that all bone grafts should be slowly resorbed and replaced with native bone over time, accumulating evidence has in fact suggested that this class of nonresorbable material may in fact be favored for certain clinical indications high-lighted later in this book Histologic evidence from clinical studies is presented with long-term follow-up, demonstrat-ing how xenografts remain stable in host tissues years follow-ing their implantation

Alloplasts

Alloplasts are synthetically developed bone grafts fabricated

in a laboratory and are derived from different tions of hydroxyapatite (HA), β-TCP, polymers, and/or

Fig 2-21 MinerOss is mineralized irradiated allograft (cortical and cancellous), with particles ranging in size from 0.6 to 1.2 mm. Fig 2-22 DBBM is the most widely used xenograft, trademarked as

Bio-Oss.

osteoconductive surface that allows cell growth and 3D bone

growth, in comparison to the other classes of bone grafts,

they have generally demonstrated inferior bone-forming

ability in a number of comparative studies As presented in

Fig 2-15, only 5% of all augmentation procedures performed

in North America are done with an alloplast These

proce-dures are utilized most frequently for “holistic” patients/

clinics that generally do not wish to partake in any cadaver/

animal materials for either personal or religious reasons

One alloplast utilized clinically is NovaBone because of

its paste-like structure (see Fig 2-23c) It is considered a

calcium phosphosilicate synthetic bone graft composed

of 70% calcium phosphosilicate, with added polyethylene

glycol, embedded in glycerin The paste is designed for

improved handling properties in specific clinical indications

Its use as a putty has therefore been favored in various

clin-ical situations, most frequently with osseodensification burs

the Versah lift, a transcrestal sinus membrane elevation and

augmentation procedures are utilized to propel the bone

graft into the sinus beneath the sinus membrane with a lower

risk of perforation by utilizing NovaBone putty Clinical

uses and case presentations are demonstrated in chapter 5

Conclusion

Bone grafting materials are the most utilized rial in dentistry It is therefore of vast importance that the regenerative properties of each graft be fully understood

biomate-to make appropriate selections during surgery Aubiomate-tografts remain the gold standard due to their excellent proper-ties of osteoinduction, osteoconduction, and osteogenesis

Their use is necessary for challenging bone augmentation procedures, and they may also be combined with allografts

or xenografts when quantities are insufficient or to take advantage of the nonresorbable properties of xenografts

Allografts, on the other hand, are available in large supplies and are the standard replacement material of choice They are utilized most frequently in dentistry (over 50% of all cases performed in North America) and are covered in great detail throughout this textbook Xenografts are an interesting class of bone grafting materials that do not necessarily possess great bone-inducing potential Never-theless, their use is widespread across dentistry because of their nonresorbable properties For these reasons, xenografts are often combined with other bone grafts as a means to hold volume following augmentation procedures The last group of bone grafting materials includes all synthetically

Fig 2-23 Alloplasts are infrequently utilized in regenerative dentistry because of

their limited bone-inducing properties (a and b) These grafts are often found with

smooth surface topographies Future research aimed at further optimizing their

regenerative properties is underway (c) NovaBone is a frequently utilized bone graft

because of its injectable putty-like properties utilized for crestal sinus augmentation

procedures (Parts a and b reprinted with permission from Miron and Zhang.38 )

Cerasorb (Curasan)

NovaBone Putty (NovaBone)

maxresorb (botiss) maxresorb (botiss)

fabricated alloplasts These grafts generally do not possess

the same bone-forming potential as the other classes and are

not commonly utilized in implant dentistry Future research

aimed at optimizing their potential with and without growth

factors is certainly an area of ongoing study, as discussed in

the following section

Growth Factors

The use of growth factors with regenerative properties has

played a pivotal role in modern medicine Their use now

expands across every field of medicine, and the number of

available bioactive factors will only continue to rise With

respect to bone medicine, epidemiologic studies have now

shown that age-related bone disorders, such as osteoporosis,

affect over 200 million people worldwide.96–102 It has further

been reported that roughly 50% of 65-year-old white and

Asian women will experience at least one osteoporotic-

related fracture within their lifetime, causing major

morbid-ity.103,104 In dentistry, osteoporosis is a major cause of quicker

alveolar bone destruction, and because of this regenerative

procedures require particular attention, especially in those

individuals who are prescribed antiresorptive medications

The significant increase in bone metabolic diseases, in

combination with traumatic injuries, necessitates specific

growth factors with bone-inducing agents to increase bone

these regenerative procedures are often further complicated

by periodontal disease, which affects approximately 40%

of the US population In such cases, growth factors are a

more recent mode of therapy providing a rapid, effective,

and predictable solution to tissue regeneration

The growth factors utilized in dentistry are divided into

two main categories: the blood-borne bioactive modifiers

and recombinant growth factors The first group contains

platelet concentrates that have been utilized in dentistry for

nearly two decades These include platelet-rich plasma (PRP),

plasma rich in growth factors (PRGF), and platelet-rich fibrin

(PRF) After PRP, the next regenerative agent approved for

commercial use over 20 years ago was enamel matrix

deriv-ative (EMD; Emdogain, Straumann) utilized for periodontal

book because its use is not indicated for bone augmentation;

however, much clinical success has been observed following

its use in periodontology Lastly, two recombinant growth

factors that have been highly utilized in dentistry with US

Food and Drug Administration (FDA) approval are

recom-binant human BMP-2 (rhBMP-2) and recomrecom-binant human

PDGF (rhPDGF) Both have shown clear advantages for bone augmentation procedures and are discussed throughout this book These growth factors have been widely utilized

in regenerative dentistry, and it is expected that the number

of clinicians taking advantage of the regenerative properties

of biologic materials will only continue to increase as more scientific evidence is discovered

Platelet concentrates in regenerative dentistry

Platelet concentrates have been utilized in regenerative medicine as a means to concentrate growth factors from blood via centrifugation Their use extends to many fields

of medicine for the management of various indications, including osteoarthritic knees, the repair of rotator cuffs, skin regeneration, treatment of burn victims, cancer therapy,

developed as a first-generation platelet formulation in the

of anticoagulants such as bovine thrombin have been shown

has been utilized in many fields of medicine to regenerate various tissue types by releasing bioactive growth factors that are known to speed soft and hard tissue regeneration

In the late 1990s, Professor Robert Marx pioneered the use of platelet concentrates (PRP) for regenerative appli-

is still utilized by certain clinicians as a means to optimize tissue regeneration Nevertheless, a group of researchers showed that anticoagulant removal could further optimize

the development of a second generation of platelet

concen-trates termed platelet-rich fibrin (PRF), later renamed

leuko-cyte platelet-rich fibrin (L-PRF), successfully accomplishing

the goal of anticoagulant removal (Fig 2-24) This second- generation platelet concentrate differs significantly from previous versions in that a high concentration of leukocytes

is found within the formulations, drastically improving not only host–immune system defense against incoming patho-gens117,123–127 but also the secretion of growth factors and

The most common growth factors found in platelet

improves the migration, proliferation, and survival of mesenchymal lineage cells TGF-β is a large superfamily of more than 30 members known to induce cell proliferation

massive synthesis of matrix molecules such as collagen-1 and

fibronectin, whether by osteoblasts or fibroblasts VEGF is

the most potent growth factor leading to new blood vessel

factor possesses individual roles in tissue regeneration, it

remains interesting to note that PDGF, one of the main

growth factors in platelet concentrates, is commercially

avail-able as a recombinant growth factor under the trademark

name GEM 21S (Lynch Biologics) for the regeneration of

various tissues,132–134 as discussed later in this chapter

Technical differences in platelet concentrates:

From PRP to PRF

While the use of platelet concentrates has gained

tremen-dous momentum as a regenerative autologous source of

growth factors for various fields of medicine, it is important

to note that their utilization spans over three decades in

preparation, concentrated platelets derived from

autolo-gous sources could be collected in plasma solutions to be

utilized in surgical sites to reach supraphysiologic doses of

popular working name platelet-rich plasma, which was then

PRP was to collect the largest and highest quantities of growth factors from platelets, PRP was fabricated with a protocol of centrifugation cycles lasting over 30 minutes and requiring the use of anticoagulants to prevent clotting

The final composition of PRP contains over 95% lets, cells known to be responsible for the active secretion

plate-of growth factors involved in initiating wound healing plate-of various cell types, including osteoblasts, epithelial cells, and connective tissue cells.122,138

Following use of PRP, several limitations were observed

The technique and the preparation required the additional use of bovine thrombin or calcium chloride in addition

to coagulation factors, and it was found that these items reduced the healing process during the regenerative phase

Furthermore, the entire protocol was technique sensitive, with several separation phases lasting sometimes upward of

1 hour, making it inefficient for everyday medical purposes

In addition, because PRP is liquid in nature, it requires a scaffold to be utilized, most notably a bone grafting material

Interestingly, studies have shown that growth factor release from PRP occurs very rapidly, whereas an optimal prefer-ence would be to deliver growth factors over an extended

Fig 2-24 (a to d) L-PRF has become widespread in regenerative dentistry because of its ability to rapidly promote angiogenesis.

a

b

d

c

These combined limitations led to the emergence of PRF,

which takes advantage of the fact that without

anticoagu-lants, a fibrin matrix that incorporates the full set of growth

factors trapped within its matrix can slowly release these

contains white blood cells, which have been shown to be

key contributors to wound healing These cells, in

combi-nation with neutrophils and platelets, are the main players

in tissue wound healing and together are able to further

enhance new blood vessel formation (angiogenesis) and

tissue formation.125,143–146

To date, numerous studies have investigated the

regener-ative potential of PRF in various medical situations With

respect to tissue engineering, it has long been proposed that

in order to maximize the regenerative potential of various

bioactive scaffolds, three components are essential:

• A 3D matrix capable of supporting tissue ingrowth

• Locally harvested cells capable of influencing tissue

growth

• Bioactive growth factors capable of enhancing cell

recruitment and differentiation within the biomaterial

surface

PRF encompasses all three of these properties, whereby

(1) fibrin serves as the scaffold surface material; (2) cells

including leukocytes, macrophages, neutrophils, and platelets

attract and recruit future regenerative cells to the defect

sites; and (3) fibrin serves as a reservoir of growth factors

that may be released over 10 to 14 days (Fig 2-25) PRF may therefore be utilized in many aspects of regenerative dentistry and is often combined with various other bioma-terials to improve tissue vascularization

L-PRF: A natural fibrin matrix and its biologic properties

The removal of anticoagulants from PRF allows for the formation of a fibrin clot during the centrifugation process

Because clotting occurs rapidly, centrifugation must take place within seconds after blood harvesting This technol-ogy therefore requires that the office is equipped with a centrifuge and a collection system

The original PRF protocol was very simple: A blood sample is taken without anticoagulant in 10-mL tubes, which are then immediately centrifuged at 750 g for 12 minutes The absence of anticoagulant implies that within a few minutes, most platelets of the blood sample in contact with the tube walls are activated to release coagulation

layer of the tube, before the circulating thrombin transforms

it into fibrin A fibrin clot is then obtained in the upper- middle portion of the tube, just between the red corpuscles

at the bottom of the tube and the acellular plasma at the top (platelet-poor plasma [PPP])

As previously mentioned, the success of this technique depends entirely on the speed of blood collection and its subsequent transfer to the centrifuge Indeed, without anticoagulants, the blood samples start to coagulate almost immediately upon contact with the tube glass, and it takes a minimum of a few minutes of centrifugation to concentrate fibrinogen in the middle and upper part of the tube Quick handling is the only way to obtain a clinically usable PRF matrix If the duration required to collect blood and launch centrifugation is overly long, failure will occur By driving out the fluids trapped in the fibrin matrix, practitioners will obtain very resistant autologous fibrin membranes

Major cell type in L-PRF: Leukocytes

Platelets are the cornerstone for cells found in each of the platelet concentrates, including L-PRF In L-PRF platelets are theoretically trapped within the fibrin network, and their 3D mesh allows for their slow and gradual release as well as

Leuko-cytes are also trapped within the L-PRF membranes, unlike

in PRP Leukocytes play a prominent role in wound healing, and several studies have now pointed to their key role in

Studies from the basic sciences have revealed the potent and

Provisional extracellular matrix Bioactive molecules

Fig 2-25 PRF supports all three aspects of tissue engineering, including

cells, a scaffold, and growth factors These are all derived naturally from the

human body when PRF is utilized These include (1) cell types (platelets,

leukocytes, and red blood cells); (2) a provisional extracellular matrix 3D

scaffold fabricated from autologous fibrin (including fibronectin and

vitronec-tin); and (3) a wide array of over 100 bioactive molecules IGF, insulin-like

growth factor; EGF, epidermal growth factor (Reprinted with permission

from Miron et al 110 )

large impact of leukocytes on tissue regeneration around

factors and serve as key regulators controlling the ability

for biomaterials to adapt to new environments

Leuko-cytes also play a large role in host defense to incoming

pathogens A study conducted following extraction of third

molars showed that the placement of PRF scaffolds into

extraction sockets resulted in a 10-fold decrease in third

study, patients receiving PRF reported less pain and less need

for analgesics when compared to controls, most notably

due to the defense of immune cells that prevent infection,

promote wound closure, and naturally reduce swelling and

associated pain felt by these patients.151

Uses of L-PRF in regenerative dentistry

It is now known that the most important factor for tissue

regeneration is not necessarily the amount of growth factor

released but the maintenance of a low and constant

gradi-ent over time As the use of L-PRF has seen a continuous

and steady increase in regenerative medicine, there has also

been great interest in utilizing this technology for a wide

variety of procedures to increase angiogenesis of tissues, an

important scenario for tissue regeneration Prior to initiating

any blood collection, it is important that all centrifuges be

prepared, open, and ready for use at the appropriate settings

Because no anticoagulants are being utilized, blood

collec-tion and centrifugacollec-tion must occur rapidly to maximize the

regenerative potential of L-PRF After centrifugation, L-PRF

membranes are removed, separated from the red clot, and

Fig 2-26 (a to h) L-PRF can be cut into small fragments and mixed with a bone grafting material to improve its angiogenic potential.

Fig 2-27 L-PRF can

be centrifuged for shorter spin times to fabricate a liquid layer

of PRF This liquid may then be mixed with bone grafting materi- als to create an L-PRF block graft for im- proved angiogenesis, handling, and stability.

a

b

transported to the L-PRF box to create barrier membranes

Additionally, L-PRF clots can be utilized to fabricate plugs (1 cm in diameter) for extraction sockets, or they can be cut into small fragments and mixed with bone grafting materials

to improve their potential for angiogenesis (Fig 2-26)

More recently, it was proposed that a liquid PRF that clots after mixing with a bone grafting material could be fabricated

by centrifuging for less time This liquid plasma layer (which remains liquid for approximately 15 minutes) is mixed with bone grafting materials to create sticky bone (Fig 2-27) This liquid version of PRF contains an even higher concentration of leukocytes and growth factors and can be utilized to improve bone grafting material angiogenesis, handling, and stability

Clinical uses and indications for L-PRF

The clinical use of L-PRF has exploded in popularity across

many fields of medicine and dentistry over the past 15 years

Most notably, L-PRF has had a major impact on tissue

regeneration for various indications in dentistry, where it

can be utilized as a fast and relatively inexpensive procedure

to aid in the regeneration of various tissues often

encoun-tered in daily clinical practice L-PRF has been studied for

augmentation procedures,157–160 for gingival recessions,161–163

for palatal wound closure,164–166 and for regeneration of

dentistry because of its ability to speed revascularization of

defect tissues and to serve as a 3D fibrin matrix capable of

further enhancing wound healing

BMP-2

BMPs are a group of pleiotropic morphogens capable of

recruiting, proliferating, and differentiating

mesenchy-mal progenitor cells toward the bone-forming osteoblast

of numerous scientific studies performed by Marshall Urist,

who analyzed the potential for demineralized bone matrix

to induce ectopic bone formation in the late 1960s and

grafts were osteoinductive by forming ectopic bone, he

later determined the factors responsible for bone formation

In the early 1970s, he published the first article describing

BMP-2 as the main protein found in bone responsible for

osteoinductivity More recently, in vitro and in vivo studies

confirm that BMP-2 remains the best growth factor capable

research has investigated the cellular signaling pathways activated through BMP It is generally accepted that BMP

2004 the FDA approved the sale of rhBMP-2 supplied with a bovine collagen sponge, sold under the trade names Infuse Bone Graft (Medtronic, United States) and InductOs (Medtronic, United Kingdom) It was originally approved for orthopedic use following a large clinical trial in which rhBMP-2 was tested on 450 patients with open tibial frac-tures and demonstrated significantly higher union rates, improved wound healing, reduced infection, and fewer

been used for a variety of dental procedures, including

procedures,187,188 extraction socket preservation,189 alveolar

clinically used BMP, rhBMP-7, was sold under the trade names OP-1 Putty (Stryker) in the United States and Osi-

demon-strates osteoinductive potential and the ability to form bone

in fibular defects and scaphoid non-unions.193,194 The potency

of rhBMP-2 and rhBMP-7 has been compared in various comparative studies, and the results show that rhBMP-2

majority of clinicians utilize Infuse Bone Graft (rhBMP-2), which is demonstrated in various clinical cases later in this book for complex defect regeneration

Control BMP-2

10 (ng)

50 100 200

Fig 2-28 rhBMP-2 can be utilized to rapidly stimulate osteoblast

differ-entiation Notice that from low concentration (10 ng) to high concentration

(200 ng), more alkaline phosphatase staining can be observed, indicating

osteoblast differentiation (Reprinted with permission from Fujioka-

Kobayashi et al 177 )

80 60 40 20 0

The delivery of rhBMP-2 for clinical applications is

extremely important Because BMPs are osteoinductive

and therefore capable of inducing bone formation in

prac-tically any tissue, it is critical that the growth factor be

prop-erly utilized A number of studies have demonstrated that

BMPs adsorb favorably to collagen when compared to bone

For these reasons, rhBMP-2 is packaged with a delivery

system utilizing collagen Infuse Bone Graft is supplied

with an absorbable collagen sponge (ACS), which has been

shown to absorb rhBMP-2 with much greater efficiency

when compared to bone grafting materials It is therefore a

requirement for those working with rhBMP-2 to dissolve

the lyophilized protein in sterile water and to adsorb the

growth factor onto the collagen sponge for a 15-minute

period to allow proper adsorption of the protein (Fig 2-30)

Today, rhBMP-2 is the most utilized recombinant growth

factor in dentistry for the regeneration of complex

osse-ous defects because of its ability to recruit mesenchymal

progenitor cells and induce their differentiation toward

recombinant human growth factors in routine dental

prac-tice has primarily been limited to oral surgeons, the rapid

rate of new bone formation following use of rhBMP-2

makes it an attractive therapeutic option for bone ation It is generally considered an expensive product, but

regener-it has the major advantage that regener-it can be utilized in lieu of autogenous bone in various clinical scenarios The specific indications for utilizing rhBMP-2 in implant dentistry are discussed throughout this book as a potential tissue engi-neering replacement strategy for autogenous bone and for the treatment of complex cases such as vertical augmentation procedures and major reconstructive surgeries

PDGF

The second most utilized biologic growth factor for tissue regeneration in dentistry has been rhPDGF Following successful use of platelet concentrates, PDGF was isolated as

a recombinant growth factor and utilized at 1,000 times the physiologic dose.112,198 Following rigorous preclinical testing, rhPDGF was granted FDA approval as the first such growth factor of its kind built from recombinant proteins.199,200 Its main action is derived following injury by promoting rapid cell migration and proliferation to defect sites and for these reasons (and much like PRP or PRF) can be utilized for

Fig 2-30 (a to c) Lyophilized BMP-2 is dissolved in sterile water for a 5-minute period Afterward, the

collagen sponge is soaked with rhBMP-2 for a period of 15 minutes to 2 hours After 15 minutes, 93%

of the protein is adsorbed to the collagen sponge (d to j) Thereafter, the sponge may be cut into smaller

fragments and, if necessary, mixed with another biomaterial such as a bone allograft.