Musculoskeletal Transplant Foundation Research Articles

Allograft Research and Transplantation: Editorial Comment

The Musculoskeletal Transplant Foundation (MTF) has sponsored research grants since the early 1990s, with the goal of increasing scientific information on allograft tissue transplantation. To foster interchange between scientists and physicians interested in transplantation, the Foundation has also supported periodic symposia in which leaders in this field have gathered for two days of scientific presentations and discussion. In September 2011, the Sixth MTF Symposium was held in Chicago, IL, USA. This symposium highlighted major themes of transplantation important to the biologic reconstruction of patients, including (1) tissue processing and transplantation, (2) transplants involving ligaments and soft tissues, (3) molecular pathways and growth factors affecting transplantation, (4) stem cells in biologic reconstruction, and (5) tissue engineering affecting transplantation. In addition to discussing advances in transplantation, the symposium program also recognized the sacrifices and generous gifts of donor families. The cochairs of the symposium, Dr. J. A. Buckwalter of the University of Iowa (Iowa City, IA, USA) and Dr. M. E. Bolander of the Mayo Clinic (Rochester, MN, USA), acknowledged the unselfish decisions all donor families make in times of crises. As guest editors, we want to quote the core of their comments from the symposium program: “Donor families have led [the field of transplantation] in a manner we intuitively understand, yet struggle to fully appreciate or comprehend. Their altruism is the true spirit of humanity. To say more seems to lessen the depth of our appreciation.” The dual role of the symposium fostered a special connection between researchers and physicians and the public they serve. A symposium is a specific collection of scientists and clinicians presenting the latest information on a particular topic. In this case, the collection is the result of MTF’s Peer Reviewed Grant Program. Twenty-four of the 25 presentations at this symposium were funded in the last 5 years by this program. In this publication, a number of manuscripts from the symposium are presented. The intriguing question that traverses all of these papers is: where are we now or what has changed since the two Guest Editors began their research on tissue transplantation in the mid-1970s? In short, we have evolved from studying macrobiologics and biomechanics in tissue incorporation to examining the influence of microbiologics on healing and manipulation of healing pathways. Nonetheless, the basic facts of incorporation of transplanted tissue remain the same, as has the rate of success in the use of allograft tissues. Tissue transplantation continues to be important in providing options in the treatment of musculoskeletal problems afflicting hundreds of thousands of patients each year. Fig. 1 Hans Burchardt, PhD, is shown. Fig. 2 William W. Tomford, MD, is shown. Knowing where we are, the followup question is: where are we going? As illustrated in this symposium, one possible direction is the application of advances in computerized engineering such as dynamic contrast enhancement (DCI)-MRI and cone tomography to evaluate angioneogenesis in bone formation. The “Holy Grail” of developing appendages in vitro or in vivo remains the ultimate goal. There are interesting beginnings as scientists are now using synthetic matrices with human stem cells to form the rudiments of appendages. In fact, the research community has clearly focused on the use of stem cells to replicate human tissues on demand. We want to thank all of the participants of the Sixth symposium for the creative interaction that occurred between physicians and scientists. We also want to thank CORR for the opportunity to include these manuscripts as peer-reviewed entities that emphasize the importance of continued research in transplantation. Inclusion in a journal of CORR’s excellence and recognition in the professional community assures the added distribution of these findings to the scientific world.

A Novel Prospective Three-Dimensional Analysis of Nasolabial Fold Augmentation

There are many products approved for aesthetic soft tissue augmentation. Despite this abundance, there is limited objective data regarding safety, longevity, and complication rates. Instead, most reports rely on subjective measures to report volume changes and outcomes, making product comparison difficult. The authors developed and validated a mathematical model to prospectively calculate and analyze three-dimensional (3D) volumetric changes associated with nasolabial fold augmentation based on human acellular dermis. Seven consecutive patients were included in this prospective review. The patients underwent nasolabial fold treatment with BellaDerm (Musculoskeletal Transplant Foundation, Edison, NJ), administered by a single surgeon. 3D photographs were obtained and analyzed with a novel mathematical model to determine absolute volumetric changes and objective longevity. Mean preoperative nasolabial fold volume was 0.17 mL. The mean one-, three-, and six-month postoperative fill volumes were 0.35, 0.19, and 0.07 mL, respectively. Fill volumes and contour changes returned to baseline by 24 weeks postoperatively in the majority of patients. The mathematical model utilized in this study provided prospective and objective data regarding longevity and volumetric changes associated with nasolabial fold augmentation. The analysis demonstrated minimal objective filler permanence beyond six months, with peak volume enhancement between one and three months. Adoption of objective 3D mathematical metrics into the assessment of soft tissue filler outcomes is critical to obtaining more accurate product-to-product comparisons.

Reversed Acellular Dermis: Failure of Graft Incorporation in Primary Tissue Expander Breast Reconstruction Resulting in Recurrent Breast Cellulitis

Sir: The use of acellular dermis in breast reconstruction has gained traction among patients. Despite its low overall complication rate, this procedure is not without risk; as with any foreign body, acellular dermis can generate a host inflammatory reaction and overt infection. The transition from inert graft to integrated tissue is dependent on vascularization and incorporation of the acellular dermis. The proper orientation of the graft is defined by placement of the dermal surface toward the vascularizing tissue. We present the first report of the clinical consequence of inadvertent placement of reversed acellular dermis during immediate expander breast reconstruction. The patient is a 60-year-old woman who underwent right skin-sparing mastectomy with sentinel lymph node biopsy, followed by immediate expander breast reconstruction with allograft acellular dermis (Flex-HD; Musculoskeletal Transplant Foundation, Edison, N.J.). There were no immediate postoperative complications. While receiving adjuvant chemotherapy, she had multiple episodes of self-limiting superficial cellulitis responsive to oral antibiotics. Ultrasound imaging revealed no evidence of fluid collection or abscess. At the routine expander/implant exchange procedure, intraoperative examination revealed capsule formation surrounding the acellular dermis graft, without significant tissue incorporation. On closer evaluation, the graft was noted to be reversed, with the tissue ingrowth dermal surface facing toward the expander. The unincorporated graft was removed. Postoperatively, the patient did not experience any further episodes of cellulitis. Pathologic evaluation of the dermal graft revealed dense foreign-body reaction without evidence of tissue revascularization (Fig. 1).Fig. 1.: Intraoperative and histologic evaluation of acellular dermal graft. (Above) Intraoperative image detailing reversed acellular dermis (grasped by tissue forceps) with absence of tissue incorporation. (Below) Histologic image of acellular dermal graft after removal detailing avascularity and inflammatory response.The incidence of cellulitis after tissue expander breast reconstruction is reportedly between 3 and 7 percent.1,2 Recently, within the breast literature, there have been reports of a latent clinical syndrome, termed “delayed breast cellulitis,” occurring months after the index mastectomy procedure.3 In our particular case, the patient did not have any of the risk factors for this syndrome. Several articles have also reported a longstanding erysipelas-like process that can occur following breast reconstruction.4 In these cases, resolution occurred gradually over months, without significant response to antibiotics. In our particular case, each episode of cellulitis was discrete, self-limited, and responsive to oral antibiotics. The transition from inert acellular dermal graft to host-integrated tissue is dependent on neovascularization of the graft, which reportedly occurs by week 12 after implantation.2 The proper orientation of the graft is dependent on matching the appropriate side of the graft to the vascularizing tissue. Electron microscopic studies indicate a demonstrable difference between acellular dermal graft surfaces: one that is more porous to enable cell infiltration and vascularization, and another that is more inert (Fig. 2). The lack of proper tissue ingrowth and revascularization is significant in our case, and suggests that graft orientation is crucial.Fig. 2.: Electron microscopic images of Flex-HD acellular dermal graft detailing the polarity differences of the graft surfaces. (Above) Porous “dermal” side, which effectively promotes incorporation and vascularization. (Below) Nonporous “epidermal” side, which is more inert. (Images courtesy of Dr. Bruce Ramshaw, Sheila Grant, and the BICAM materials team at the University of Missouri, Columbia, Mo.).In summary, there is a danger that reversed acellular dermis may not incorporate after primary tissue expander reconstruction. The lack of sufficient neovascularization may create a chronic foreign body reaction that presents as episodic cellulitis without concomitant seroma or abscess. This cause should be considered when such a constellation of symptoms presents in the setting of acellular dermis use in tissue expander breast reconstruction. Kamaldeep Heyer, M.D. Donald W. Buck, II, M.D. Caroline Kato, B.S. Seema A. Khan, M.D. Murad Alam, M.D. John Y. S. Kim, M.D. Division of Plastic and Reconstructive Surgery Northwestern University Feinberg School of Medicine Chicago, Ill. DISCLOSURE The authors have no conflicts of interest with regard to this research.

Laparoscopic adjustable gastric banding after previous Roux-en- Y gastric bypass

Weight regain and inadequate weight loss after gastric bypass remain significant concerns, with potential effects on multiple quality measures. Poor restriction of oral intake owing to dilation of the small gastric pouch or the gastrojejunostomy is a potential cause of recidivism. Operative revision of the pouch or anastomosis can be technically difficult, carrying significant perioperative risk. Placement of a laparoscopic adjustable gastric band around the gastric pouch is an alternative for intervention in this patient population. We reviewed the pertinent data and describe our technique for laparoscopic placement of an adjustable gastric band after previous gastric bypass. The essential aspects of intraoperative anatomy, dissection, and decision making are covered, including the options for band fixation according to a particular patient’s history of previous gastric bypass and remnant tube gastrostomy. Methods The present case (and the corresponding video) was that of a 53-year-old morbidly obese woman with multiple comorbidities, including back pain, depression, and significant gastroesophageal reflux disease, with changes in Barrett’s esophagus after laparoscopic Nissen fundoplication. She had undergone laparoscopic Roux-en-Y gastric bypass with takedown of her previous fundoplication and decompression of her gastric remnant by tube gastrostomy. She had recovered well from that operation, with improvement of her gastroesophogeal reflux disease symptoms. However, she experienced poor (50%) excess weight loss during long-term follow-up, despite ongoing dietary evaluation and behavior modification counseling. Her principle complaint was an inadequate sense of restriction of oral intake. She completed an extensive workup, including a contrast swallow study and flexible upper endoscopy, which revealed a dilated gastrojejunostomy measuring approximately 3 cm in diameter. She subsequently underwent endoscopic suture plication of her gastrojejunostomy 29 months after her bypass, with minimal additional weight loss. After discussion of her options for additional intervention, she elected to undergo placement of an adjustable gastric band over her bypass. The pneumoperitoneum and our standard laparoscopic adjustable gastric band (LAGB), 5-port setup, were established. We then proceeded with careful dissection of the anterior small gastric pouch, Roux limb, and gastrojejunostomy away from the overlying liver, which was then elevated with a Nathanson retractor. A combination of ultrasonic, electrosurgical, and blunt dissection was used to identify the pars flaccida and angle of His. The pars flaccida was divided to reveal the right crus and distinguish it from the more laterally lying inferior vena cava. An opening for the retrogastric tunnel was created by dissecting along the medial aspect of the right crus. An esophageal dissector was then passed bluntly through the retrogastric tunnel and articulated to expose the tip at the angle of His. An AP standard LapBand (Allergan, Irvine, CA) was introduced into the patient’s abdomen and passed through the retrogastric tunnel using the esophageal dissector. The LapBand tubing and buckle were secured in the standard fashion. This patient’s gastric remnant remained fixed to the anterior abdominal wall with extensive adhesions from the previous tube gastrostomy, precluding safe use for band fixation. Therefore, we fashioned a piece of DermaMatrix (Musculoskeletal Transplant Foundation, Edison, NJ), measuring approximately 2 cm 8 cm, and secured it with permanent 2-0 Ethibond suture (Ethicon, Somerville, NJ) to

Molecular Biology and Therapeutics in Musculoskeletal Oncology*

Musculoskeletal oncology encompasses a broad array of diseases and treatment challenges. The most important issue facing a patient with a sarcoma is cure. Traditional cytotoxic chemotherapy has evolved empirically over the last several decades. While substantial improvements have been made in cure rates for pediatric patients with sarcoma, cure rates have plateaued at considerably less than 100% and chemotherapy for adult patients is far less effective. Starting with cytogenetic analysis and, more recently, the molecular dissection of tumors, it has become obvious that “sarcoma” is not a diagnosis per se but a group of diseases. Adult soft-tissue sarcoma alone comprises many different histologic subtypes. A better understanding of the biology of tumors at the molecular level has brought forth the possibility of targeted therapy, prompting the American Academy of Orthopaedic Surgeons (AAOS) and the Orthopaedic Research Society (ORS) to hold the Molecular Biology and Therapeutics in Musculoskeletal Oncology Research Symposium in September 2008. In contrast to the broad-spectrum drugs that are used in traditional chemotherapy, targeted therapy is biologically based and attempts to counteract the exact abnormality of the tumor cell. The types of abnormalities include overactive cell-surface receptors, which are part of the signaling cascades that drive growth; the secretion of proteins that stimulate angiogenesis; and the loss of function of tumor-suppressor genes that normally restrain growth. The types of therapeutics used include monoclonal antibodies, drugs that block overactive receptors, and gene-therapy techniques. The concept is that instead of using the same drugs for all patients with a particular stage of disease, the treatment would be personalized on the basis of the biologic abnormalities. The difficulties include the fact that there are many molecular abnormalities in any one tumor, with heterogeneity from one cell to the next; genetic instability leading to additional abnormalities over time; an overlap of biochemical pathways between normal physiologic processes and tumor growth; and a lack of therapeutics capable of reversing or blocking many of the molecular abnormalities found in tumors. Another limitation of the strategy is that blocking the effect of a molecular abnormality does not usually cure the patient in the traditional sense but can suppress tumor growth for some period of time. Fortunately, sometimes there are synergies when targeted, biologically based therapy is combined with cytotoxic chemotherapy, leading to a higher chance of cure. The AAOS-ORS Molecular Biology and Therapeutics in Musculoskeletal Oncology Research Symposium was held in Salt Lake City, Utah, in September 2008, to address these issues. In addition to the AAOS and ORS sponsorship, the symposium received grant support from the Orthopaedic Research and Education Foundation, the National Cancer Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; collaborative sponsorship from the Musculoskeletal Tumor Society and the WWWW Foundation, Inc. (QuadW); and industry support from the Musculoskeletal Transplant Foundation, Stryker, and Biomet. The organizers cast a wide net so as to include leaders in the field representing academia, the National Institutes of Health, the U.S. Food and Drug Administration, industry, leading cancer institutions, and cancer-related organizations, both from within and outside the traditional orthopaedic boundaries. A complete list of participants and their affiliations is included in the Appendix. The objectives of the symposium were to establish the state of the art of molecular biology and therapeutics in musculoskeletal oncology, identify barriers and potential solutions to advance the field, establish research priorities, and provide an educational forum that could foster collaborations for new and established investigators. The meeting was organized around the major diseases in musculoskeletal oncology; current topics in cancer biology, including genomic screening; and novel therapies. The following summary of the presentations and deliberations of the breakout sessions is provided as a record of the meeting and to guide prioritization of research funding.

New Approaches to Allograft Transplantation: Editorial Comment

The Musculoskeletal Transplant Foundation Symposium, held in Vancouver, B.C. in October 2007, was the fifth invitational meeting since 1993. These Symposia have reflected the Foundation’s commitment to the science of allografts and bioconstructs. This 5th International Symposium celebrated the Foundation’s 20th year and recognized the founders’ dreams for a viable institution capable of furthering scientific advances in transplantation. Through the support of internal and external research, the ultimate goal has been to advance the medical treatment of patients. Dr. J. Buckwalter of the University of Iowa and Dr. M. Bolander of the Mayo Clinic were the architects and co-chairs for this international meeting. In addition to being members of the Musculoskeletal Transplant Foundation (MTF) Board of Directors, these individuals are well-known, both nationally and internationally, as advocates of scientific research. At the opening of the Symposium, Dr. William F. Enneking and Dr. V. Frankel were formally acknowledged as the two founding members of MTF who have provided key stewardship since its inception in 1987. Both Drs. Enneking and Frankel are recognized nationally and internationally as leaders in the fields of orthopaedics, education, and research. Their vision prompted the development of a peer-review grant program that encouraged young investigators to enter today’s competitive research environment. More than a grant program, this program also emphasized presentation and publication. Since 1993, the MTF grant program has awarded over $20 million for allograft and bioconstruct research to men and women representing more than 112 institutions. The five International Symposia are landmarks of this program. The 5th Symposium is of even greater importance since 32 of the 40 presentations were recipients of awards within the last seven years. The Symposium’s three sessions emphasized cartilage, soft tissue, and bone transplantation. The 40 presentations represented the work of researchers from Europe, South America, Canada, and the United States. Each session was characterized by the intermixture of basic science, tissue banking safety, or the technological improvements being explored with hard and soft tissue engineering. Twenty-three manuscripts were submitted for publication, with the 20 published here best representing the entire spectrum of the Symposium. The articles in CORR have been reordered from the original presentation to better group the topics of tissue transplantation. Thus, the reader will first encounter clinical work, such as the use of transplants in children, followed by research with autologous cartilage cell transplants in a synthetic matrix. New clinical information is also presented on the characteristics of graft failure in allografts, and the lack of immunogenic consequences to tissue transplants. The futuristic topics in tissue transplantation are of unusual interest to both professionals and the lay public. Three articles emphasize the modification of natural remodeling characteristics usually associated with transplants to enhance incorporation. Another focuses on interference with the first phase of cortical bone remodeling, namely resorption. The question remains: Does modifying the resorptive phase allow for normal incorporation and biomechanical properties of the transplants? The hard and soft tissue engineering field is the forerunner of change in today’s transplantation research. Therefore, the articles on growth factors, the use of stem cells, nano meshes and microspheres are of particular interest. This modern engineering includes newer technologies capable of assessing biological materials in vivo using a dynamic contrast-enhanced MRI to quantify vascularity, or the testing of transplant materials in an in vivo bioreactor. It seems we have an obligation to provide continuing support to evaluate transplants. Decisions must be made regarding their success in relation to the use of synthetics, which seem to emerge from many directions. It is possible the future of tissue transplants will demonstrate a greater merging with synthetics and pharmaceuticals, whereby transplants will act as carriers of future technologies. Undoubtedly, research in the next 5 decades will dazzle us even more than the scientific changes we have witnessed in the past 50 years. The most surprising advances will likely come from the direction that research takes unexpectedly by incorporating newer technologies. The recognition in the 60’s and 70’s that musculoskeletal tissue transplantation could be performed with relative immunological impunity led to tissue banking. The maturing of the newest experimental advances will lead to twists and turns not yet comprehended. I thank all of the investigators for their contributions to the Symposium. The publication process has become more detailed and exacting, and these changes reflect the greater expectations demanded from all of us to better serve the medical needs of the public. Finally, I want to express to all of you involved in the Symposium and the publication, my appreciation for your efforts and my gratitude for your dedicated support.

Effects of Irradiated Frozen Allogenic Bone and Musculoskeletal Transplant Foundation on Bone Formation in Human Fetal Osteoblasts

Effects of Irradiated Frozen Allogenic Bone and Musculoskeletal Transplant Foundation on Bone Formation in Human Fetal Osteoblasts

Intact genetic material is present in commercially processed cadaver allografts used for pubovaginal slings.

We determined the presence, quantitated the concentration and assessed the length of DNA present in 4 commercially available human cadaver allografts. We evaluated 10 tissue samples from each of 4 commercial sources of human allograft (Mentor Corp., Santa Barbara, California; Musculoskeletal Transplant Foundation, Edison, New Jersey; Regeneration Technologies, Inc., Alachua, Florida; and Life Cell Corp., Woodlands, Texas) for intact DNA segments. All allograft samples underwent a standard extraction technique (proteinase K/sodium dodecyl sulfate/phenol) to isolate genetic material. Spectrophotometry evaluation was done to quantify DNA concentrations. Polymerase chain reaction was performed to amplify the retrieved DNA material. Agarose gel electrophoresis was performed to determine the size of DNA fragments. Of the 49 samples tested from all 4 commercial sources of human allograft fascia 39 (97.5%) contained DNA of 400 to 2,000 bp segments. A 400 bp DNA segment was present in 9 Mentor, 10 Musculoskeletal Transplant Foundation, 10 Regeneration Technologies and 10 Life Cell samples. A 700 bp DNA segment was present in 10 Musculoskeletal Transplant Foundation, 10 Regeneration Technologies and 10 Life Cell allografts. A 2,000 bp DNA segment was present in 10 Life Cell tissues. Intact genetic material was present in all 4 commercially processed human allografts. Tissue processing did not completely eliminate intact DNA segments. The size of the intact DNA and the concentration of DNA varied widely based on tissue processing methods.

Tissue Donor Selection and Safety

Authors of recent reports in the medical literature indicate that allograft-associated infection primarily is attributable to violations of proper tissue processing procedures, and illustrate the need for effective quality assurance systems to avoid transplantation of potentially infectious tissue. I describe the experience of the members of the Musculoskeletal Transplant Foundation with the selection, the processing, and the safety of bone and tissue donors for allograft implantation. In 2002, the Musculoskeletal Transplant Foundation screened 10,497 potential donors, but only 4431 (42%) met stringent criteria for recovery. After recovery, another 10% of the donors were rejected, usually because of positive infectious disease tests (45%) or an autopsy finding (31%) that rendered the tissues unsuitable for transplantation. Procedures used by the Musculoskeletal Transplant Foundation for ensuring safety of the tissue and for investigating reports of putative infection are described. The Musculoskeletal Transplant Foundation has had no confirmed cases of allograft-associated infection in over 2 million units transplanted during the past 15 years.

Safety and FDA Regulations for Musculoskeletal Allografts

The Musculoskeletal Transplant Foundation Symposium held in September 2003, in Edinburgh, Scotland provided the opportunity for an orthopaedic surgeon experienced in tissue banking and musculoskeletal allograft transplantation to summarize to orthopaedic colleagues the past and current efforts made by the Food and Drug Administration to ensure the safety of allograft tissues, aspects of tissue banking, concerns of allograft safety and future Food and Drug Administration proposals. The review allows an orthopaedic surgeon an understanding of allograft safety issues and provides information for better informed consent to be obtained by the orthopaedic surgeon from the recipient patient.

Intact Genetic Material is Present in Commercially Processed Cadaver Allografts Used for Pubovaginal Slings

We determined the presence, quantitated the concentration and assessed the length of DNA present in 4 commercially available human cadaver allografts. We evaluated 10 tissue samples from each of 4 commercial sources of human allograft (Mentor Corp., Santa Barbara, California; Musculoskeletal Transplant Foundation, Edison, New Jersey; Regeneration Technologies, Inc., Alachua, Florida; and Life Cell Corp., Woodlands, Texas) for intact DNA segments. All allograft samples underwent a standard extraction technique (proteinase K/sodium dodecyl sulfate/phenol) to isolate genetic material. Spectrophotometry evaluation was done to quantify DNA concentrations. Polymerase chain reaction was performed to amplify the retrieved DNA material. Agarose gel electrophoresis was performed to determine the size of DNA fragments. Of the 49 samples tested from all 4 commercial sources of human allograft fascia 39 (97.5%) contained DNA of 400 to 2,000 bp segments. A 400 bp DNA segment was present in 9 Mentor, 10 Musculoskeletal Transplant Foundation, 10 Regeneration Technologies and 10 Life Cell samples. A 700 bp DNA segment was present in 10 Musculoskeletal Transplant Foundation, 10 Regeneration Technologies and 10 Life Cell allografts. A 2,000 bp DNA segment was present in 10 Life Cell tissues. Intact genetic material was present in all 4 commercially processed human allografts. Tissue processing did not completely eliminate intact DNA segments. The size of the intact DNA and the concentration of DNA varied widely based on tissue processing methods.

Bone-graft substitutes: facts, fictions, and applications.

It is estimated that more than 500,000 bone-grafting procedures are performed annually in the United States, with approximately half of these procedures related to spine fusion. These numbers easily double on a global basis and indicate a shortage in the availability of musculoskeletal donor tissue traditionally used in these reconstructions (Fig. 1). Fig. 1: United States trends in musculoskeletal tissue donors. Source: United Network for Organ Sharing and the Musculoskeletal Transplant Foundation. This reality has stimulated a proliferation of corporate interest in supplying what is seen as a growing market in bone-substitute materials (Fig. 2). These graft alternatives are subjected to varying degrees of regulatory scrutiny, and thus their true safety and effectiveness in patients may not be known prior to their use by orthopaedic surgeons. It is thus important to gain insight into this emerging class of bone-substitute alternatives. Fig. 2: United States sales of bone graft and bone substitutes. Source: Orthopedic Network News, industry estimates. The biology of bone grafts and their substitutes is appreciated from an understanding of the bone formation processes of osteogenesis, osteoinduction, and osteoconduction. Graft osteogenesis: The cellular elements within a donor graft, which survive transplantation and synthesize new bone at the recipient site. Graft osteoinduction: New bone realized through the active recruitment of host mesenchymal stem cells from the surrounding tissue, which differentiate into bone-forming osteoblasts. This process is facilitated by the presence of growth factors within the graft, principally bone morphogenetic proteins (BMPs). Graft osteoconduction: The facilitation of blood-vessel incursion and new-bone formation into a defined passive trellis structure. All bone graft and bone-graft-substitute materials can be described through these processes. Fresh autogenous cancellous and, to a lesser degree, cortical bone are benchmark graft materials that allograft and bone substitutes attempt to match in in vivo performance. They incorporate all of the above properties, are …

Editorial Comment

The following articles are a partial representation of subjects discussed at the Charles H. Herndon, MD International Symposium on Bone and Soft Tissue Allografts sponsored by the Musculoskeletal Transplant Foundation that was held in Washington, DC, April 30 to May 2, 1999. It is the guest editors' pleasure to dedicate the symposium and this work to the memory of Charles H. Herndon, MD, an outstanding orthopaedic surgeon and leader. The symposium is divided into two components that cover issues of adult reconstruction and issues of spine and trauma. Each component starts with a review of relevant basic science followed by descriptions and commentary on specific clinical applications. Within the adult reconstruction component, structural and particulate bone grafts are discussed. Within the spine and trauma component, mineralized and demineralized bone grafts are discussed. Bone allografts have become routine in certain clinical applications and, in many ways, the work presented at this symposium shows that current questions are about which graft and surgical procedure to use, rather than whether to use an allograft. Allografts have been proven to be reliable and safe components in the surgical treatment of many orthopaedic problems. Although there certainly are exciting new technologies, such as recombinant protein or gene therapy, it is the editors' belief that these new technologies most likely will be adjuncts and enhancers of allografts for the foreseeable future, rather than replacements for them. Sharon Stevenson, DVM, PhD La Jolla, CA Allan E. Gross, MD Ontario, Canada

Bone apposition onto oral implants in the sinus area filled with different grafting materials. A histological study in beagle dogs.

The placement of oral implants into jaw bone has a high predictability provided an adequate bone volume surrounding the implant is present to ensure primary stability and resistance to functional loading forces after completion of osseointegration. In the distal area of the maxilla, an adequate bone volume is often lacking because of the proximity of the sinus cavities. The aim of this study was to evaluate histologically the simultaneous placement of endosseous implants into the sinus cavity and the surgical elevation of the sinus floor including filling the cavity with different grafting materials. In 9 sinus areas of 5 beagle dogs, 9 titanium implants (ITI Dental Implant System) were placed, and the void space of the sinus cavity was filled simultaneously with either demineralized freeze-dried human cortical bone (Musculoskeletal Transplant Foundation), resorbable hydroxyapatite (Osteogen) or natural cancelleous bovine bone mineral (Bio-Oss). To study bone formation, fluorochrome markers (tetracycline HCl and calcein green) were used at 2 and 8 weeks. Clinically, all implants healed uneventfully, and 5 months after implant placement the dogs were killed for histologic evaluation. All implants exhibited osseointegration within the pre-existing cortical bone of the sinus floor. The implants surrounded by freeze-dried bone xenografts yielded no formation of new bone, whereas the sites with hydroxyapatite or natural bovine bone mineral demonstrated newly formed bone with direct contact at the implant surface. The average extent of bone to implant contact was 25% (SD = 10.6%) and 27% (SD = 8.8%), respectively in relation to the length of the originally denuded implant surface.(ABSTRACT TRUNCATED AT 250 WORDS)