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biologics studies

Biologics Studies
AlloDerm™ Regenerative Tissue Matrix
Acellular Dermal Matrix for Mucogingival Surgery: A Meta-Analysis

Ricardo Gapski, Christopher Allen Parks & Hom-Lay Wang


Background:
Many clinical studies revealed the effectiveness of acellular dermal matrix (ADM) in the treatment of mucogingival defects. The purpose of this meta-analysis was to compare the efficacy of ADM-based root coverage (RC) and ADM-based increase in keratinized tissues to other commonly used mucogingival surgeries.


Methods:
Meta-analysis was limited to randomized clinical trials (RCT). Articles from January 1, 1990 to October 2004 related to ADM were searched utilizing the MEDLINE database from the National Library of Medicine, the Cochrane Oral Health Group Specialized Trials Registry, and through hand searches of reviews and recent journals. Relevant studies were identified, ranked independently, and mean data from each were weighted accordingly. Selected outcomes were analyzed using a meta-analysis software program. The significant estimates of the treatment effects from different trials were assessed by means of Cochrane's test of heterogeneity.


Results:


  • Few RCT studies were found to compile the data. In summary, selection identified eight RCT that met the inclusion criteria. There were four studies comparing ADM versus a connective tissue graft for root coverage procedures, two studies comparing ADM versus coronally advanced flap (CAF) for root coverage procedures, and two studies comparing ADM to free gingival graft in augmentation of keratinized tissue.
  • There were no statistically significant differences between groups for any of the outcomes measured (recession coverage, keratinized tissue formation, probing depths, and clinical attachment levels).
  • The majority of the analyses demonstrated moderate to high levels of heterogeneity. 4) Considering the heterogeneity values found among the studies, certain trends could be found:
    • three out of four studies favored the ADM-RC group for recession coverage;
    • a connective tissue graft tended to increase keratinized tissue compared to ADM (0.52-mm difference; P = 0.11);
    • there were trends of increased clinical attachment gains comparing ADM to CAF procedures (0.56-mm difference; P = 0.16).

Conclusions:
Differences in study design and lack of data precluded an adequate and complete pooling of data for a more comprehensive analysis. Therefore, considering the trends presented in this study, there is a need for further randomized clinical studies of ADM procedures in comparison to common mucogingival surgical procedures to confirm our findings. It is difficult to draw anything other than tentative conclusions from this meta-analysis of ADM for mucogingival surgery, primarily because of the weakness in the design and reporting of existing trials.


© J Periodontol 2005;76:1814-1822.


Management of Gingival Recession by the Use of an Acellular Dermal Graft Material: A 12-Case Series

A. Santos, G. Goumenos & A. Pascual


Background:
Different soft tissue defects can be treated by a variety of surgical procedures. Most of these techniques require the palatal area as a donor site. Recently, an acellular dermal graft has become available that can substitute for palatal donor tissue.


Methods:
This study describes the surgical technique for gingival augmentation and root coverage and the results of 12 clinical cases. A comparison between the three most popular mucogingival procedures for root coverage is also presented.


Results:
The results of the 12 patients and the 26 denuded surfaces have shown that we can obtain a mean root coverage of 74% with the acellular dermal graft. Thirteen out of the 26 denuded surfaces had complete root coverage. The average increase in keratinized tissue was 1.19 mm. It seems that the long-term results of the cases are stable.


Conclusion:
The proposed technique of root coverage with an acellular dermal graft can be a good alternative to soft tissue grafts for root coverage, and it should be part of our periodontal plastic surgery armamentarium.


© J Periodontol 2005;76:1982-1990.


A 2-Year Follow-Up of Root Coverage Using Subpedicle Acellular Dermal Matrix Allografts and Subepithelial Connective Tissue Autografts

A. Hirsch, M. Goldstein, J. Goultschin, B.D. Boyan & Z. Schwartz


Background:
Coverage of roots exposed by gingival recession is one of the main objectives of periodontal reconstructive surgery. A large variety of mucogingival grafting procedures are available. However, the long-term effectiveness of this procedure is still not clear. This study compared the effectiveness of subpedicle acellular dermal matrix allografts with subepithelial connective tissue autografts in achieving root coverage 2 years postoperatively.


Methods:
One hundred one (101) patients were treated with dermal matrix allografts (mean age, 28.4 ± 0.7 years; mean recession, 4.2 mm) and 65 patients treated with connective tissue graft (mean age, 30.1 ± 1.4 years; mean recession, 4.9 mm). All patients underwent full periodontal evaluation and presurgical preparation, including oral hygiene instruction and scaling and root planing.


The exposed roots were thoroughly planed and covered by a graft without any further root treatment or conditioning. There were no differences in the average age, time of follow-up, or gender between the two groups. Patients were evaluated periodically between 1 and 2 years. Residual recession and defect coverage were assessed.


Results:
Mean residual root recession after root coverage with acellular dermal matrix allograft was 0.2 ± 0.04 mm, with defect coverage of 95.9 ± 0.9%. Frequency of defect coverage was 82.2%. Root coverage was 98.8% ± 0.2%, resulting in a frequency of root coverage of 100%. Gain in keratinized gingiva was 2.2 ± 0.04 mm and attachment gain was 4.5 ± 0.1 mm per patient.


Connective tissue autografts resulted in mean residual root recession of 0.1 ± 0.04 mm, with percent defect coverage of 97.8% ± 0.6% and frequency of defect coverage of 95.4%. Root coverage was 99.1% ± 0.2%, and frequency of root coverage was 100%. Gain in keratinized gingiva was 3.0 ± 0.1 mm and attachment gain was 5.3 ± 0.2 mm per patient.


No significant differences in final recession and root coverage between the two treatment methods were found. However, autografts resulted in significant increases in defect coverage, keratinized gingival gain, attachment gain, and residual probing depth. The clinical results were stable for the 2-year follow-up period.


Conclusions:
These results indicate that coverage of root by subpedicle acellular dermal matrix allografts or subepithelial connective tissue autografts is a very predictable procedure which is stable for 2 years post-operatively. However, subepithelial connective tissue autografts resulted in significant increases in defect coverage, keratinized gingival gain, attachment gain, and residual probing depth.


© J Periodontol 2005;76:1323-1328.


Reconstructive Surgical Management of an Amalgam Tattoo Using an Acellular Dermal Matrix Graft: Case Reports

Terrence J Griffin, Susan A Banjar & Wai S Cheung, DDS, MS


Abstract:
Amalgam tattoos in the gingiva and mucosa can interfere with esthetics and present a barrier to surface-to-bone contact at implant sites. Two clinical cases are used to illustrate the effectiveness of acellular dermal matrix allografts in the treatment of these lesions. Very esthetic results were obtained with minimal discomfort and postoperative complications because of the prevention of a second surgical site or additional procedure.


© Compendium 2005;26:853-859.


Complete Root Coverage at Multiple Sites Using an Acellular Dermal Matrix Allograft

Michael J Mehlbauer & Henry Greenwell


Abstract:
This study reports results of root coverage treatment with a coronally positioned flap and an acellular dermal matrix allograft. The same protocol was followed as in a previous university study to determine if the results could be duplicated in a private practice setting.

Complete root coverage was obtained on most defects. Use of an acellular dermal matrix allograft avoided the postoperative morbidity associated with harvesting palatal connective tissue. The unlimited supply of the allograft allowed extended flaps to achieve multiple site root coverage, which proved to be a practical and predictable procedure in these cases. 


© Compendium 2005;26:727-733.


Histologic Evaluation of Autogenous Connective Tissue and Acellular Dermal Matrix Grafts in Humans

Lewis C. Cummings, Wayne B. Kaldahl & Edward P. Allen


Background:
The clinical success of root coverage with autogenous connective tissue CT) or acellular dermal matrix (ADM) has been well documented. However, limited histological results of CT grafts have been reported, and a case report of a human block section has been published documenting an ADM graft. The purpose of this study is to document the histological results of CT grafts, ADM grafts, and coronally advanced flaps to cover denuded roots in humans.


Methods:
This study included four patients previously treatment planned for extractions of three or more anterior teeth.  Three teeth in each patient were selected and randomly designated to receive either a CT or ADM graft beneath a coronally advanced flap (tests) or coronally advanced flap alone (control). Six months postoperatively block section extractions were performed and the teeth processed for histologic evaluation with hematoxylin-eosin and Verhoeff's stains.


Results:
Histologically, both the CT and ADM were well incorporated within the recipient tissues. New fibroblasts, vascular elements, and collagen were present throughout the ADM, while retention of the transplanted elastic fibers was apparent. No effect on the keratinization or connective tissue organization of the overlying alveolar mucosa was evident with either graft. For both materials, areas of cemental deposition were present within the root notches, the alveolar bone was essentially unaffected, and the attachments to the root surfaces were similar.


Conclusion: Although CT and ADM have a slightly different histological appearance, both can successfully be used to cover denuded roots with similar attachments and no adverse healing.


© J Periodontol 2005; 76: 178-186.


Acellular Dermal Matrix and Hydroxyapatite in Prevention of Ridge Deformities after Tooth Extraction

Sonia M. Luczyszyn, DDS, MS, Vula Papalexiou, DDS, MS, Arthur B. Novaes Jr., DDS, MS, DSc, Marcio F. M. Grisi, DDS, MS, DSc, Sergio L. S. Souza, DDS, MS, DSc & Mario Taba Jr., DDS, MS, DSc


The aim of this study was to evaluate the role of acellular dermal matrix graft (ADMG) acting as a membrane, associated with a resorbable hydroxyapatite (RHA) in bone regeneration to prevent ridge deformities after tooth extraction.  Fifteen patients who had at least 2 noncontiguous, uniradicular teeth indicated for extraction were selected. In group I, the extraction sockets were covered by ADMG alone; and in group II, the alveoli were filled with RHA before the placement of the ADMG.


After 6 months, re-entry surgeries and biopsies were performed. Although ridge thickness had been preserved in both groups, the means were significantly greater (P <0.05) for group II when compared to group I (6.8 ± 1.26 and 5.53 ± 1.06). The histologic analysis showed small bone formation in some samples for group II, where the presence of a highly vascularized fibrous connective tissue surrounding the particles was a common finding.


Based on the results, it can be concluded that the ADMG was able to preserve ridge thickness and that the additional use of RHA favored the preservation of the ridges along with an increase in the width of keratinized tissue. 


© Implant Dent 2005;14:176-184


Hard and Soft Tissue Augmentation in Implant Therapy Using Acellular Dermal Matrix

Terrence J. Griffin, DMD, Wai S. Cheung, DDS, MS & Hiroshi Hirayama, DDS, DMD, MS


The use of acellular dermal matrix to correct soft and hard tissue defects involving implants is described through three case reports. Correction of a ridge deformity caused by a root fracture, submerging of an existing implant and correction of recession defects around adjacent teeth, and ridge preservation for implant placement are presented.


The use of acellular dermal matrix prevented the need for a second surgical site for donor material and the possible attendant postoperative complications. It also enhanced patient comfort and satisfaction with the procedure. All three cases demonstrated excellent functional and esthetic results for both the patients and professionals involved in the therapy. 


© Int J Periodontics Restorative Dent 2004;24:352-361


A 6-Month Comparative Clinical Study of a Conventional and a New Surgical Approach for Root Coverage With Acellular Dermal Matrix

Raquel R.M. Barros, Arthur B. Novaes Jr., Márcio F.M. Grisi, Sérgio L.S. Souza, Mário Taba Jr., & Daniela B. Palioto


Background:
The acellular dermal matrix graft (ADMG) has become widely used in periodontal surgeries as a substitute for the subepithelial connective tissue graft (SCTG). These grafts exhibit different healing processes due to their distinct cellular and vascular structures.


Therefore the surgical technique primarily developed for the autograft may not be adequate for the allograft. This study compared the clinical results of two surgical techniques - the "conventional" and a modified procedure - for the treatment of localized gingival recessions with the ADMG.


Methods:
A total of 32 bilateral Miller Class I or II gingival recessions were selected and randomly assigned to test and control groups. The control group received the SCTG and the test group the modified surgical technique. Probing depth (PD), relative clinical attachment level (RCAL), gingival recession (GR), and width of keratinized tissue (KT) were measured 2 weeks prior to surgery and 6 months post-surgery.


Results:
Both procedures improved all the evaluated parameters after 6 months. Comparisons between the groups by Mann-Whitney rank sum test revealed no statistically significant differences in terms of CAL gain, PD reduction, and increase in KT from baseline to 6-month evaluation. However, there was a statistically significant greater reduction of GR favoring the modified technique (P = 0.002). The percentage of root coverage was 79% for the test group and 63.9% for the control group.


Conclusion:
We conclude that the modified technique is more suitable for root coverage procedures with the ADMG since it had statistically significant better clinical results compared to the traditional technique.


© J Periodontol 2004;75:1350-1356


Coronally Positioned Flap With or Without Acellular Dermal Matrix Graft in the Treatment of Class I Gingival Recessions: A Randomized Controlled Clinical Study

Antonieta De Queiroz Córtes, Ângela Guimarã Martins, Francisco H. Nociti Jr., Antonio Wilson Sallum, Marcio Z. Casati & Enilson A. Sallum


Background:
The aim of this study was to clinically evaluate the treatment of Class I gingival recessions by coronally positioned flap with or without acellular dermal matrix allograft (ADM).


Methods:
Thirteen patients with comparable bilateral Miller Class I gingival recessions (3.0 mm) were selected. The defects were randomly assigned to one of the treatments: coronally positioned flap and acellular dermal matrix (ADM group) or coronally positioned flap alone (CPF group).


The clinical parameters included: probing depth (PD), clinical attachment level (CAL), recession height (RH), recession width (RW), height of keratinized tissue (HKT), thickness of keratinized tissue (TKT), plaque index (PI), and gingival index (GI). The measurements were taken before the surgeries and after 6 months.


Results:
The mean baseline recession was 3.4 mm and 3.5 mm for ADM group and CPF group, respectively. After 6 months, both treatments resulted in significant root coverage (P <0.01), reaching an average of 2.6 mm (76%) in the ADM group and 2.5 mm (71%) in the CPF group.


The difference in recession reduction between treatments was not statistically significant. There were no statistically significant differences between the treatments in PD, CAL, RH, RW, and HKT. However, the mean TKT gain was 0.7 mm for the ADM group and 0.2 mm for the CPF group (P <0.01).


Conclusion:
It can be concluded that both techniques could provide significant root coverage in Class I gingival recessions; however, a greater keratinized tissue thickness can be expected with ADM.


© J Periodontol 2004;75:1137-1144


A Short-Term and Long-Term Comparison of Root Coverage With an Acellular Dermal Matrix and a Subepithelial Graft

Randall J. Harris


Background:
Obtaining predictable and esthetic root coverage has become important. Unfortunately, there is only a limited amount of information available on the long-term results of root coverage procedures. The goal of this study was to evaluate the short-term and long-term root coverage results obtained with an acellular dermal matrix and a subepithelial graft.


Methods:
An a priori power analysis was done to determine that 25 was an adequate sample size for each group in this study. Twenty-five patients treated with either an acellular dermal matrix or a subepithelial graft for root coverage were included in this study. The short-term (mean 12.3 to 13.2 weeks) and long-term (mean 48.1 to 49.2 months) results were compared.


Additionally, various factors were evaluated to determine whether they could affect the results. This study was a retrospective study of patients in a fee-for-service private periodontal practice. The patients were not randomly assigned to treatment groups.


Results:
The mean root coverages for the short-term acellular dermal matrix (93.4%), short-term subepithelial graft (96.6%), and long-term subepithelial graft (97.0%) were statistically similar. All three were statistically greater than the long-term acellular dermal matrix mean root coverage (65.8%). Similar results were noted in the change in recession.


There were smaller probing reductions and less of an increase in keratinized tissue with the acellular dermal matrix than the subepithelial graft. None of the factors evaluated resulted in the acellular dermal graft having a statistically significant better result than the subepithelial graft.


However, in long-term cases where multiple defects were treated with an acellular dermal matrix, the mean root coverage (70.8%) was greater than the mean root coverage in long-term cases where a single defect was treated with an acellular dermal matrix (50.0%).


Conclusions:
The mean results with the subepithelial graft held up with time better than the mean results with an acellular dermal matrix. However, the results were not universal. In 32.0% of the cases treated with an acellular dermal matrix, the results improved or remained stable with time. 


© J Periodontol 2004;75:734-743


The Clinical Effect of Acellular Dermal Matrix on Gingival Thickness and Root Coverage Compared to Coronally Positioned Flap Alone

James G. Woodyard, Henry Greenwell, Margaret Hill, Connie Drisko, John M. Iasella & James Scheetz


Background:
The primary aim of this randomized, controlled, blinded, clinical investigation was to compare the coronally positioned flap (CPF) plus an acellular dermal matrix (ADM) allograft to CPF alone to determine their effect on gingival thickness and percent root coverage.


Methods:
Twenty-four subjects with one Miller Class I or II buccal recession defect of 3 mm were treated with a CPF plus ADM or a CPF alone. Multiple additional recession sites were treated with the same flap procedure, and all sites were studied for 6 months. Tissue thickness was measured at the sulcus base and at the mucogingival junction of all teeth, with an SDM ultrasonic gingival thickness meter.


Results:
For the ADM sites, mean initial recession of 3.46 mm was reduced to 0.04 mm for defect coverage of 3.42 mm or 99% (P <0.05).  For the CPF group, mean initial recession of 3.27 mm was reduced to 1.08 mm for defect coverage of 2.19 mm or 67% (P <0.05). The difference between ADM and CPF groups was statistically significant (P <0.05).  Marginal soft-tissue thickness was increased by 0.40 mm (P <0.05) for the ADM group, whereas the CPF group remained essentially unchanged.


Keratinized tissue was increased for the ADM group by 0.81 mm (P <0.05), whereas the CPF group increased by 0.33 mm (P >0.05). No additional root coverage was gained due to creeping attachment between 2 and 6 months for either group.


Conclusions:
Treatment with a CPF plus an ADM allograft significantly increased gingival thickness when compared with a CPF alone. Recession defect coverage was significantly improved with the use of ADM. 


© J Periodontol 2004; 75:44-56


Extraction Sockets and Implantation of Hydroxyapatites With Membrane Barriers: A Histologic Study

Stuart Froum, DDS, Sang-Choon Cho, DDS, Nicolas Elian, DDS, Edwin Rosenberg, DDS, Michael Rohrer, DDS & Dennis Tarnow, DDS


The purpose of this pilot study was to investigate the effect on extraction socket healing when an absorbable hydroxyapatite (AH) and a nonabsorbable anorganic bovine bone mineral (ABB) covered with either an acellular dermal matrix allograft (ADMA) or expanded polytetrafluoroethylene (ePTFE) membrane barrier were left exposed to the oral cavity. Following tooth extraction, a total of 16 sockets in 15 patients with deficient buccal plates of 5 mm were randomly divided into 4 treatment groups:


  • AH covered with ADMA,
  • AH covered with an ePTFE membrane,
  • ABB covered with ADMA, and
  • ABB covered with an ePTFE membrane.

Primary coverage was not attempted or obtained in any of the 16 treated sockets. Six to 8 months post extraction at the time of implant placement, histologic cores of the treatment sites were obtained. These cores were processed, stained with Stevenel's blue/ van Gieson's picro fuchsin, and histomorphometrically analyzed.


Vital bone, connective tissue and marrow, and residual graft particles were reported as a percentage of the total core. The mean vital bone was 34.5% (AH with ADMA), 41.7% (ABB with ADMA), 27.6% (ePTFE and AH), and 17.8% (ePTFE and ABB). The average percentage of vital bone in the 8 sockets covered with ADAMA was 38% compared with an average percentage vital bone of 22% in the 8 sockets covered with ePTFE membrane barriers.


Because of the small number of specimens in the 4 groups, statistical analysis was not possible. However, in this pilot study, ADMA-covered sites resulted in more vital bone present 6 to 8 months post socket treatment than obtained in the ePTFE- covered sites regardless of bone replacement materials used. Further research is warranted to see if these results show a similar difference in bone-to-implant contact after implant placement.


© Implant Dent 2004;13:153-164


Root Coverage of Advanced Gingival Recession: A Comparative Study Between Acellular Dermal Matrix Allograft and Subepithelial Connective Tissue Grafts

Haim Tal, Ofer Moses, Ron Zohar, Haya Meir & Carlos Nemcovsky


Background:
Acellular dermal matrix allograft (ADMA) has successfully been applied as a substitute for free connective tissue grafts (CTG) in various periodontal procedures, including root coverage. The purpose of this study was to clinically compare the efficiency of ADMA and CTG in the treatment of gingival recessions 4 mm.


Methods:
Seven patients with bilateral recession lesions participated. Fourteen teeth presenting gingival recessions 4 mm were randomly treated with ADMA or CTG covered by coronally advanced flaps. Recession, probing depth, and width of keratinized tissue were measured preoperatively and 12 months postoperatively. Changes in these clinical parameters were calculated within and compared between groups and analyzed statistically.


Results:
Baseline recession, probing depth, and keratinized tissue width were similar for both groups. At 12 months, root coverage gain was 4.57 mm (89.1%) versus 4.29 mm (88.7%) (P = NS), and keratinized tissue gain was 0.86 mm (36%) versus 2.14 mm (107%) (P <0.05) for ADMA and CTG, respectively. Probing depth remained unchanged (0.22 mm/0 mm), with no difference between the groups.


Conclusions:
Recession defects may be covered using ADMA or CTG, with no practical difference. However, CTG results in significantly greater gain of keratinized gingiva. 


© J Periodontol 2002;73:1405-1411

Mem-Lok® abstracts
A resorbable, reconstituted type I collagen membrane for guided tissue regeneration and soft-tissue augmentation

D Yuen, C Junchaya, G Zuclich, JB Ulreich, HB Lin, ST Li


Introduction:
There are several requirements that a resorbable membrane should meet in order for it to be useful for guided tissue regeneration (GTR) and soft tissue augmentation applications. The membrane should be resorbable, have sufficient mechanical strength to permit suturing of the membrane to the host, be permeable to nutrients and be biocompatible. The particular medical application will define the specifications of each requirement. We present here a new resorbable, reconstituted type I collagen membrane for use in GTR or as a patch for soft tissue augmentation. The results of a comparison between this membrane and a collagen membrane currently marketed for GTR applications are also discussed.


Methods:
Collagen Membrane: Two types of collagen membrane were fabricated from purified type I collagen fibers. The collagen fibers were dispersed in an acid solution (pH 2.5), homogenized, filtered, reconstituted, freeze dried, crosslinked, and sterilized by irradiation. Characterization: Suture pull-out strength: A size 3-0 silk suture was passed through the membrane, 1.5 cm x 2.0 cm, at about 3 mm from the edge and a loop was tied. The membrane was hydrated in 0.01 M phosphate buffer, pH 7.0, for 10 minutes. The loop was attached to a force gauge (Chatillon, Greensboro, NC) and the sample was secured onto a clamping fixture. The sample was pulled at a rate of 1 inch per minute until the suture was pulled out. The force was recorded.


Permeability: The permeability of the membrane was determined by inserting a sample, 2.0 cm x 2.0 cm, into a specially designed chamber, which is separated into two isolated compartments. On one side of the chamber, a fixed volume of phosphate buffered saline (PBS) containing 50 µg of carbonic anhydrase (CA) (MW 29,000) per ml was added. The opposite side was filled with the same volume of PBS only. The chamber containing the membrane was allowed to equilibrate for 24 hours and the CA assay was conducted on the side initially without CA by the Coomassie plus assay.* In Vivo Resorption Studies: A total of 11 rats were used. Each rat received a 1cm2 membrane implanted subcutaneously. Animals were sacrificed at 4, 8, 12, and 24 weeks after implantation. The explants were evaluated histologically for collagen membrane remaining, tissue reaction and new collagen deposition using standard histologic techniques. Biocompatibility: Biocompatibility testing was conducted on the collagen membrane in accordance with FDA guidelines.


Results:
Table 1 summarizes the characterization studies on the two types of collagen membranes, A and B compared to the commercial product Biomend®. The average suture pull-out strength was 350 g and 290 g, respectively for A and B. This strength is significantly higher than for Biomend®. The total resorption time was obtained through extrapolation via curve fit of the experimental data. The resorption times for the membranes were 27 and 18 weeks respectively for A and B. Both membranes A and B were significantly more stable in vivo than Biomend®. Both membranes A and B were permeable to CA, which has a size similar to the Biomend® pore structure, and biocompatible.


Discussion:
The use of a membrane for GTR in oral surgery often requires the membrane to be permeable for nutrients but not cells so that the membrane can serve as a cell barrier to guide the specific tissue regeneration. Both membranes A and B and Biomend® can serve that function. Very often, the membrane is required to be stabilized with sutures. In this regard, membranes A and B offer advantages over Biomend® in that they have a higher suture pull-out strength. In addition, the in vivo, stability of membranes A and B are significantly longer than the Biomend®. Although the significance of this difference is not known, it would be logical to expect that a longer in vivo stability may provide an additional margin of efficacy in using the membrane as a cell barrier. The characteristics of membranes A and B also offer potential applications as soft tissue augmentation devices such as patch material for hernia and heart surgeries.


* Bradford, M.M. Anal. Biochem. 72:248, 1976.
© Sixth World Biomaterials Congress Transactions

MinerOss® abstracts
Clinical and Histologic Outcomes After the Use of a Novel Allograft for Maxillary Sinus Augmentation: A Case Series

Gustavo Avila, DDS, MS, PhD, Rodrigo Neiva, DDS, MS, Carl E. Misch, DDS, MDS, PhD(hc), Pablo Galindo-Moreno, DDS, PhD, Erika Benavides, DDS, PhD, Ivan Rudek, DDS and Hom-Lay Wang, DDS, MSD, PhD


Purpose:
To document the clinical and histologic outcomes of sinus augmentation using a novel allogenic bone substitute as a sole grafting material.


Materials:
Patients in need of sinus augmentation before implant placement were recruited for this study. Sinus augmentation procedures were performed following a lateral approach, using a freeze-dried allograft as the only grafting material. Patients were followed up postoperatively for 6 months. Plaque score, wound healing, and patient discomfort were recorded at each follow-up visit. Implants were placed between 6 and 7 months after sinus augmentation and restored 6 months later. Bone core biopsy specimens were harvested at the time of implant placement and processed for histologic and histomorphometrical analysis. Vital bone, remaining allograft (RA) particles, and nonmineralized tissue percentages were assessed on each sample. Results were expressed as mean percentages with SD.


Results:


Of the 23 sinus patients, 20 patients underwent sinus augmentation surgery. All patients had satisfactory postoperative healing in the absence of complications. A total of 39 implants were placed. One implant failed and was replaced 3 months later. Histologic analysis revealed the presence of well-organized lamellar bone, in direct contact with RA particles. Mean vital bone was 23.02 ± 19.11%, mean RA was 22.25 ± 20.30%, and average nonmineralized tissue was 54.73 ± 13.51%. Conclusion: Clinical and histologic findings support the suitability of an allograft consisting of a combination of cortical and cancellous chips for sinus augmentation procedures.


© Implant Dent 2010;19:330-341


The influence of the Bucco-palatal distance on Sinus Augmentation Outcomes

Gustavo Avila, Hom-Lay Wang, Pablo Galindo-Moreno, Carl E. Misch, Robert A. Bagramian, Ivan Rudek, Erika Benavides, Ildefonso Moreno-Riestra, Thomas Braun and Rodrigo Neiva


Background:
Maxillary sinus augmentation is one of the most reliable implant site development options to increase vertical bone height. However, graft consolidation requires adequate angiogenesis and migration of cells involved in osteogenesis and bone remodeling. It is speculated that these biologic events are greatly determined by the dimensions of the maxillary sinus cavity. Hence, the purpose of this study is to assess the influence of the distance from the lateral to the medial wall of the maxillary sinus on the outcomes of sinus augmentation procedures.


Methods:
Maxillary sinus augmentation is one of the most reliable implant site development options to increase vertical bone height. However, graft consolidation requires adequate angiogenesis and migration of cells involved in osteogenesis and bone remodeling. It is speculated that these biologic events are greatly determined by the dimensions of the maxillary sinus cavity. Hence, the purpose of this study is to assess the influence of the distance from the lateral to the medial wall of the maxillary sinus on the outcomes of sinus augmentation procedures.


Results:
Twenty-one patients underwent sinus augmentation for a total of 24 sinuses; however, the data analyzed contained only one sinus per patient. One sinus developed an infection after grafting, resulting in a 96% success rate for the sinus grafting procedure. Twenty sinuses were used in the final statistical analysis. Histomorphometric analysis revealed that mean %VB was 22.71 ± 19.08, mean percent of remaining allograft 23.39 ± 20.85, and average percent of non-mineralized connective tissue was 53.90 ± 13.23. Analysis of the correlation between %VB and BPD by linear regression, using the actual values of BPD showed a strong negative association (R2=0.141;P<0.001).


Conclusion:
The findings suggested that %VB formation after maxillary sinus augmentation is inversely proportional to the sinus BPD.


© J Periodontol 2010:81:1041-1050


Histological, Histomorphometric, and Radiographic Evaluation of a Sinus Augmentation with a New Bone Allograft: A Clinical Case Report

Ricardo Gapski, BDS, DDS, MS, Carl Misch, DDS, MS, PhD, David Stapleton, DDS, Stephanie Mullins, DDS, MS, Charles Cobb, DDS, MS, PhD, Asvin Vansanthan, DDS, MS and Marc Reissner, DDS


Purpose:
This case report documents the histological, histomorphometric, and radiographic effects of a few radiated-preserved bone allograft for sinus elevation procedure.


Materials and Methods:
This unique bone substitute differs from other forms of bone allograft processed through the standard cryopreservation method. Histology from bone biopsy core samples revealed newly formed bone with a well-organized lamellar bone structure in general and remaining particles were observed in contact with surrounding newly-formed bone.


Results:
±6.77% graft resorption from baseline to 6 months.


Conclusions:
The outcome of this report suggests that this bone allograft could be successfully used in sinus lifting procedures. It encourages further research of this radiated-preserved bone allograft material in oral and maxillofacial reconstruction.


© Implant Dent 2008;17:430-438


Grafton® DBM abstracts
Clinical and Histological Evaluation of an Allogeneic Bone Matrix for the Treatment of Periodontal Osseous Defects

James T. Mellonig, DDS, MS


The objective of this study was to evaluate the potential of an allogeneic bone matrix (ABM) Grafton® to regenerate new bone, new cementum, and a new periodontal ligament around teeth previously contaminated by bacterial plaque. Four patients with chronic advanced periodontitis and scheduled for full mouth extraction were accrued. One patient was exited from the study before any therapy began. One tooth with an intraosseous defect in each patient was selected for treatment.


Clinical measurements of probing depth, gingival recession, and clinical attachment level were made. After flap reflection, a root notch was placed at the apical level of calculus, the root debrided, and ABM was inserted into the defect. After six months of healing the teeth were removed en bloc and evaluated histologically for a new attachment apparatus. Two of the three teeth demonstrated regeneration of new bone, cementum, and periodontal ligament.


Accepted for publication: International Journal of Periodontics and Restorative Dentistry 2006


Osteoinductivity of Commercially Available Demineralized Bone Matrix: Preparations in a Spine Fusion Model

Peterson, Brett, MD; Whang, Peter, MD; Inglesias, Robero, MD; Wang, Jeff, MD & Lieberman, Jay, MD.


Background:
Although autogenous bone is the most widely used graft material for spinal fusion, demineralized bone matrix preparations are available as alternatives or supplements to autograft. They are prepared by acid extraction of most of the mineralized component, with retention of the collagen and noncollagenous proteins, including growth factors.


Differences in allograft processing methods among suppliers might yield products with different osteoinductive activities. The purpose of this study was to compare the efficacy of three different commercially available demineralized bone matrix products for inducing spinal fusion in an athymic rat model.


Methods:
Sixty male athymic rats underwent spinal fusion and were divided into three groups of eighteen animals each. Group I received Grafton Putty; Group II, DBX Putty; and Group Ill, AlloMatrix Injectable Putty. A control group of six animals (Group IV) underwent decortication alone.


Six animals from each of the three experimental groups were killed at each of three intervals (two, four, and eight weeks), and the six animals from the control group were killed at eight weeks. At each of the time-points, radiographic and histologic analysis and manual testing of the explanted spines were performed.


Results:
The spines in Group I demonstrated higher rates of radiographically evident fusion at eight weeks than did the spines in Group III or Group IV (p < 0.05). Manual testing of the spines at four weeks revealed variable fusion rates (five of six in Group I, two of six in Group II, and none of six in Group Ill). At eight weeks, all six spines in Group I, three of the six in Group II, and no spine in Group III or IV had fused. Histologic analysis of the spines in Groups I, II, and III demonstrated varying amounts of residual demineralized bone matrix and new bone formation. Group-1 spines demonstrated the most new bone formation.


Conclusions:
This study demonstrated differences in the osteoinductive potentials of commercially available demineralized bone matrices in this animal model.


Clinical Relevance:
Comparative clinical testing of demineralized bone matrices is indicated in order to determine which preparations are best suited for promoting successful spinal fusion in humans.


© The Journal of Bone and Joint Surgery. 2004;86-A:2243-2250


A Comparative Review of the Osteoinductivity of Four Formulations of Allogeneic Demineralized Bone Matrix

When properly processed, demineralized bone matrix (DBM) graft materials can take advantage of two healing pathways or mechanisms. First, DBM allografts can provide a suitable matrix for cells to infiltrate, populate and produce new bone through "osteoconductive" healing.


DBM can also aid in the healing response through "osteoinductive" pathways in which mesenchymal cells are stimulated by native bioactive molecules to differentiate into bone forming cells. Demineralization is a necessary process to produce a bone allograft with osteoinductive capabilities. However, not all demineralization processes effectively or consistently produce osteoinductive allografts. Some tissue processing techniques can affect both the presence and robustness of the osteoinductive capacity of the resulting demineralized end product.


This review examines the osteoinductivity of four formulations of human DBM from three tissue-processing facilities. These studies utilized a well-characterized athymic rat model comparing the osteoinductive potential of Osteofil® (Regeneration Technologies Inc., Alachua, FL.), Dynagraft® (GenSci Regeneration Sciences Inc., Toronto, Canada) and Grafton® DBM (Osteotech Inc., Eatontown, NJ).


Both the Putty and Gel formulations of Grafton consistently showed a strong osteoinductive response via the anticipated pathway of endochronal bone formation. In contrast, Osteofil showed osteoinductive activity, but produced less cartilage (14 days) and bone (28 days) than an equivalent volume of Grafton. DynaGraft failed to show consistent osteoinduction. The inability of a material to form new bone in this animal model has been shown to have a negative effect on bone healing. A material that elicits an osteoinductive response is more likely to lead to a satisfactory clinical outcome.


© University of Texas of San Antonio, San Antonio, TX. and The Cleveland Clinic Foundation, Cleveland, OH.


Tissue Banking of Bone Allografts Used in Periodontal Regeneration

Committee on Research, Science and Therapy, of the American Academy of Periodontology


This review paper evaluated the current knowledge of the safety and effectiveness of bone allograft materials, including demineralized freeze-dried bone allograft (DFDBA). Bone allografts have been widely used in periodontal therapy and continue to be used in contemporary clinical practice. Most bone banks adhere to the guidelines of the American Association of Tissue Banks (AATB) with respect to procurement, processing and sterilization of bone grafts. There have been no reports of viral contamination or acquired pathology from DFDBA, and thus, DFDBA appears to be safe from disease transmission.


Clinical results using DFDBA have been variable based on evidence from clinical reports due to the wide variability in bone graft processing. Factors such as terminal sterilization of the bone allograft material, processing methods, and donor age influence the bone inductive ability of DFDBA.


The only definitive assay of osteoinduction remains implantation of the DFDBA in a tissue that otherwise would not form bone, such as an immunodeficient rat or mouse muscle. A quantitative histologic analysis must be performed of the amount of new bone that is formed in association with the implanted DFDBA. In vitro assays used to assess bone induction ability must be relied on with caution. 


© J Periodontol 2001;72:834-838.


Prospective Comparison of Commercially Available Demineralized Bone Matrix for Spinal Fusion

Wang, J.C., Davies, M.R., Kanim, L.E.A., Ukatu, C.J., Dawson, E.G., Lieberman & J.R. UCLA School of Medicine


Demineralized bone matrix derived from human tissues has demonstrated the ability to aid in the stimulation of an osteoinductive response allowing for improved bone growth and fusion. The study is the first highly controlled prospective test to compare the osteoinductive ability of three commercially available demineralized bone matrix products in a spinal fusion model.


By at least 6 weeks and as early as 4 weeks, Osteofil and Grafton® alone demonstrated posterolateral fusion manually, radiographically and histologically while Dynagraft, local human cortical bone, or autogenous rat iliac crest bone did not.


© Orthopaedic Research Society. 2001.


Histologic Analysis of Implant Sites After Grafting with Demineralized Bone Matrix Putty and Sheets

Callan, D.P., Salkeld, S.L. & Scarborough, N.L.


Grafting to restore lost alveolar bone is frequently used to enable placement of endosseous implants and improve cosmesis. Conflicting reports concerning the osteoinductivity of demineralized bone matrix (DBM) and historical use of synthetic bone graft substitutes has limited the use of DBM in oral and maxillofacial applications. Implant placement after bone grafting provides the unique opportunity to biopsy and histologically evaluate new bone formation.


Bone grafting of the mandible or maxilla was performed to fill extraction sockets and restore ridge structures in a consecutive series of eight patients. DBM prepared as malleable putty (Grafton DBM Putty) or flexible sheets (Grafton DBM Flex) was used.


Biopsies were taken at re-entry, and histologic analysis determined the amount and quality of regenerated bone. Extensive new bone formation and minimal residual bone graft matrix were observed at an average of five months postoperative. The pattern of new bone maturity and remodeling varied by patient and the time in situ. Putty and Flex regenerated excellent bone height and width for the placement of dental implants, were easy to handle intraoperatively, and readily conformed to bony defects. 


© Implant Dentistry, 9:36-42, 2000.


Early Success of Nonautologous Sinus Grafting in Implant Patients

Neugarten, J.M.


The purpose of this investigation was to evaluate the success of allographic and xenographic grafted maxillary sinuses and the success of immediate and delayed endosseous implants placed into the grafted sinuses. Twelve sinuses were grafted with a combination of cancellous xenograft (Bio-Oss) and demineralized freeze-dried bone allograft (Grafton).  A total of 41 implants were placed into the augmented sinuses.


Core biopsy specimens were obtained at the time of implant placement. All 12 sinus grafts were successful.  The overall success rate of endosseous implants placed into the grafts was 93%. The sinus graft core biopsies histologically confirmed the presence of active osteoblasts as well as new mature bone within the graft.


© Oral Abstract Session 11: Reconstruction / Implants, AAOMS 2000


Osteogenic Activity of OP-1 Bone Morphogenetic Protein (BMP-7) in a Human Fibular Defect

Geesink, R.G.T., Hoefnagels N.H.M. & Bulstra, S.K.


This study is a prospective, randomized double-blind study in 24 patients undergoing high tibial osteotomy to evaluate the effectiveness of human recombinant osteogenic protein (OP-1) on a collagen type-1 carrier in a critically-sized fibular defect. The study had two phases, each evaluated by clinical, radiological, and DEXA methods during the first postoperative year.


The first concerned the validation of the model of the fibular defect, using positive (Grafton DBM) and negative (untreated) controls. The second phase concerned the osteogenic potential of OP-1 on collagen type-I vs. collagen type-I alone.


The results of the first phase established the critically-sized nature of the defect. In the untreated group, no bony changes were observed while, in the Grafton DBM bone group, formation of new bone was visible from six weeks onwards. The results of the second phase showed no significant formation of new bone in the presence of collagen alone, while in the OP-1 group, all patients except one showed formation of new bone from six weeks onwards. This provided the osteogenic activity of OP-1 in a validated critically-sized human defect.


© The Journal of Bone & Joint Surgery, 81-B:710-718, 1999.


New Formulations of Demineralized Bone Matrix as a More Effective Graft Alternative in Experimental Posterolateral Lumbar Spine Arthrodesis

Martin Jr., G.J., Boden, S.D., Titus, L. & Scarborough, N.L.


The objective of this study was to determine the efficacy of two new formulations of demineralized bone matrix in an animal model. The flowable gel form of Grafton (Osteotech, Eatontown, NJ) demineralized bone matrix has been shown to have osteoinductive properties in various models and currently is used clinically as bone graft material in posterolateral lumbar spine arthrodesis.


Two new formulations of Grafton, one made of flexible sheets (Flex) and the other made in a malleable consistency (Putty), have improved handling characteristics compared with the gel form.


Posterolateral intertransverse process athrodesis was performed on 108 skeletally mature New Zealand white rabbits using corticocancellous bone graft harvested from the iliac crest and/or DBM of various formulations. The new flexible sheet and malleable putty forms of demineralized bone matrix were effective as graft extender and graft enhancer in a well-characterized rabbit model of posterolateral lumbar spine fusion.


The malleable putty form and flexible sheet form were able to function as a complete graft substitute, with the latter performing superiorly in this challenging animal spine fusion model. These newer formulations of Grafton appear to have a greater capacity to form bone through osteoconductive pathways than the original gel form or autogenous bone graft alone in the rabbit.


© Spine, 24:637-645, 1999.


Allograft Safety: Viral Inactivation with Bone Demineralization

Scarborough, N.L., White, E.M., Hughes, J.V., Manrique, A.J. & Poser, J.W.


A study was performed to validate the effectiveness of a bone demineralization process with respect to its inactivation of viruses. The viruses selected for study included human immunodeficiency virus (HIV), duck hepatitis B virus (a model for human hepatitis B), bovine viral diarrheal virus (a model for human hepatitis C), human cytomegalovirus, and human poliovirus (a model for small nonenveloped viruses, e.g., hepatitis A).


This study was performed in compliance with Good Laboratory Practice regulations using validation methodology similar to that used to ensure the safety of blood derivatives and other products. Use of the bone demineralization process described in this report resulted in a reduction in infectivity of greater than one million (106) for all viruses and as much as one trillion (1012) for the poliovirus. 


© Contemporary Orthopaedics, 31:4, 1995.


Induction of Bone by a Demineralized Bone Matrix Gel: A Study in a Rat Femoral Defect Model

Feighan, J.E., Davy, D., Prewett, A.B. & Stevenson, S.


Demineralized bone matrix contains osteoinductive factors and stimulates filling of gaps and defects with bone; however, it is difficult to handle by itself and various preparations have been tested. Demineralized bone matrix with a gel consistency is now available for clinical use. We studied, in a femoral segment defect in the rat, the effects of rat demineralized bone matrix gel with and without ceramic substratum.


This preparation is analogous to the human demineralized bone matrix in the same carrier, used clinically for humans.


One hundred adult male Fischer rats were divided into 10 experimental groups. Independent variables including the presence or absence of hydroxyapatite ceramic cylinders, the presence of demineralized bone matrix in carrier or carrier alone (glycerol), and the duration of observation (1,2, and 4 months). Defects filled with the gel alone had significantly higher radiographic scores for host-graft union at 4 months, compared with ceramic with the gel, ceramic alone, or carrier alone.


Demineralized bone matrix gel significantly increased the total histologic score for host-graft union, whether ceramic was present or not, and a three-way interaction occurred among ceramic, the gel, and time. Demineralized bone matrix gel was an effective inducer of new bone in this model.


An additional substratum was not required; in fact, significantly more bone was formed in the absence of the ceramic cylinder. Neither the gel, nor the ceramic were impediments to revascularization of the defect. Host-graft union was enhanced by demineralized bone matrix gel but not by the ceramic cylinder. 


© Journal of Orthopaedic Research, 13:881-891,1995.