Collagen Membrane for Guided Cortical Bone Regeneration: Characterization, Preclinical and Proof of Concept Clinical Studies

Abstract Background: Treatment of cortical bone defects is a clinical challenge. Guided bone regeneration (GBR), commonly used in oral in maxillofacial dental surgery, may show promise for orthopedic application in repair of cortical defects. However, a limitation in the use of GBR for cortical bone defects is the lack of an ideal scaffold that provides sufficient mechanical support to bridge the cortical bone with minimal interference in the repair process. We have developed a new collagen membrane, CelGroTM, for use in GBR. We report the material characterisation of CelGroTM, and evaluate the performance of CelGroTM in translational preclinical and clinical studies. Methods: Scanning electron microscopy (SEM), micro computed tomography (micro-CT) and transmission electron microscopy (TEM) were used to examine the structural morphology of CelGroTM. Purity and biochemical composition of CelGroTM was evaluated by Western-blot, immunohistochemistry and confocal microscopy. Physical and chemical properties of CelGroTM were examined and compared with another commercially available collagen membrane. The pre-clinical evaluation was conducted using a cortical bone defect model in the New Zealand white rabbit. Cortical bone regeneration in defects of the femoral diaphysis were evaluated at 30 days and 60 days after intervention, by micro-CT and histology. A clinical study to evaluate the performance of CelGroTM in GBR for treatment of bone augmentation surrounding dental implants was also performed. The clinical outcomes were evaluated by semi quantitative tissue condition assessments and cone-beam computed tomography (CBCT) scan. Results: CelGroTM has a bilayer structure of different fibre alignment and is composed almost exclusively of type I collagen. CelGroTM was found to be completely acellular and a clinically significant xenoantigen, α -gal, was not detected. CelGroTM displayed less deformity and better mechanical strength as compared to Bio-Gide ® . In the preclinical study, CelGroTM demonstrated enhanced bone-modelling activity and cortical bone healing. Micro-CT evaluation showed early bony bridging over the defect area 30 days post-operatively, and nearly complete restoration of mature cortical bone at the bone defect site 60 days post- operatively. Histological analysis at day 60 after surgery further confirmed that CelGroTM enables bridging of the cortical bone defect by induction of newly-formed cortical bone. It appears that CelGroTM showed better cortical alignment and reduced porosity at the defect interface compared to Bio-Gide®. Owning the fact that selection of orthopedic patients with cortical bone defects is complex, we conducted the proof of concept clinical study in a total of 16 dental implants which were placed in 10 participants receiving GBR. The results showed that there were with no complications or adverse events observed. CBCT evidenced efficiency of the CelGroTM scaffold for GBR for the dental implants, showing significantly decreased 2 distance from the implant shoulder to first bone/implant contact (DIB) and increased horizontal thickness of facial bone wall (HT). Conclusion: The findings of our study demonstrate that CelGroTM is an ideal membrane for GBR not only in oral maxillofacial reconstructive surgery but also in orthopedic applications. Details of clinical trial registration: “Single centre, open-label, pilot study of Celgro(tm) collagen membrane for guided bone regeneration around exposed implants in patients undergoing dental implant surgery”; Registration ID: ACTRN12615000027516; Date of registration: 19/01/2015; URL: https://anzctr.org.au/ACTRN12615000027516.aspx

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Effect of Gellan Gum/Tuna Skin Film in Guided Bone Regeneration in Artificial Bone Defect in Rabbit Calvaria

Materials ◽

10.3390/ma13061318 ◽

2020 ◽

Vol 13 (6) ◽

pp. 1318

Author(s):

Seunggon Jung ◽

Hee-Kyun Oh ◽

Myung-Sun Kim ◽

Ki-Young Lee ◽

Hongju Park ◽

...

Keyword(s):

Bone Regeneration ◽

Bone Defect ◽

Bone Defects ◽

Guided Bone Regeneration ◽

Gellan Gum ◽

Collagen Membrane ◽

New Bone Formation ◽

Average Cell ◽

Beta Tricalcium Phosphate

It is necessary to prevent the invasion of soft tissue into bone defects for successful outcomes in guided bone regeneration (GBR). For this reason, many materials are used as protective barriers to bone defects. In this study, a gellan gum/tuna skin gelatin (GEL/TSG) film was prepared, and its effectiveness in bone regeneration was evaluated. The film exhibited average cell viability in vitro. Experimental bone defects were prepared in rabbit calvaria, and a bone graft procedure with beta-tricalcium phosphate was done. The film was used as a membrane of GBR and compared with results using a commercial collagen membrane. Grafted material did not show dispersion outside of bone defects and the film did not collapse into the bone defect. New bone formation was comparable to that using the collagen membrane. These results suggest that the GEL/TSG film could be used as a membrane for GBR.

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Guided Bone Regeneration in Calvarial Bone Defects Using Polytetrafluoroethylene Membranes

The Cleft Palate-Craniofacial Journal ◽

10.1597/1545-1569_1995_032_0311_gbricb_2.3.co_2 ◽

1995 ◽

Vol 32 (4) ◽

pp. 311-317 ◽

Cited By ~ 18

Author(s):

Carles Bosch ◽

Birte Melsen ◽

Karin Vargervik

Keyword(s):

Bone Regeneration ◽

Bone Defect ◽

Dura Mater ◽

Bone Defects ◽

Guided Bone Regeneration ◽

Parietal Bone ◽

Bony Defect ◽

Calvarial Bone ◽

Double Membrane ◽

Single Membrane

Guided bone regeneration is defined as controlled stimulation of new bone formation in a bony defect, either by osteogenesis, osteoinduction, or osteoconduction, re-establishing both structural and functional characteristics. Bony defects may be found as a result of congenital anomalies, trauma, neoplasms, or infectious conditions. Such conditions are often associated with severe functional and esthetic problems. Corrective treatment is often complicated by limitations in tissue adaptations. The aim of the investigation was to compare histologically the amount of bone formed in an experimentally created parietal bone defect protected with one or two polytetrafluoroethylene membranes with a contralateral control defect. A bony defect was created bilaterally in the parietal bone lateral to the sagittal suture in 29 6-month-old male Wistar rats. The animals were divided into two groups: (1) In the double membrane group (n=9), the left experimental bone defect was protected by an outer polytetrafluoroethylene membrane under the periosteum and parietal muscles and an inner membrane between the dura mater and the parietal bone. (2) In the single membrane group (n=20), only the outer membrane was placed. The right defect was not covered with any membrane and served as control. The animals were killed after 30 days. None of the control defects demonstrated complete or partial bone regeneration. In the single membrane group, the experimental site did not regenerate in 15 animals, partially in four, and completely in one. In the double membrane group, six of the experimental defects had complete closure with bone, two had partial closure, and one no closure. The use of two membranes protecting the bone edges of the parietal defect from the overlying tissues and underlying brain enhanced bone regeneration in experimental calvarial bone defects. The biologic role of the dura mater may not be of critical importance in new bone regeneration in these calvarial bone defects.

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Contour changes after guided bone regeneration of large non-contained mandibular buccal bone defects using deproteinized bovine bone mineral and a porcine-derived collagen membrane: an experimental in vivo investigation

Clinical Oral Investigations ◽

10.1007/s00784-017-2214-z ◽

2017 ◽

Vol 22 (3) ◽

pp. 1273-1283 ◽

Cited By ~ 3

Author(s):

I. Sanz-Martin ◽

L. Ferrantino ◽

F. Vignoletti ◽

J. Nuñez ◽

N. Baldini ◽

...

Keyword(s):

Bone Regeneration ◽

Bone Mineral ◽

Bone Defects ◽

Guided Bone Regeneration ◽

Collagen Membrane ◽

Bovine Bone ◽

Bovine Bone Mineral ◽

Deproteinized Bovine Bone Mineral ◽

Deproteinized Bovine Bone

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Evaluation of Guided Bone Regeneration Using the Bone Substitute Bio-Oss® and a Collagen Membrane in a Rat Cranial Bone Defect Model

Journal of Hard Tissue Biology ◽

10.2485/jhtb.27.79 ◽

2018 ◽

Vol 27 (1) ◽

pp. 79-84 ◽

Cited By ~ 1

Author(s):

Shin Kasuya ◽

Shihoko Inui ◽

Nahoko Kato-Kogoe ◽

Michi Omori ◽

Kayoko Yamamoto ◽

...

Keyword(s):

Bone Regeneration ◽

Bone Defect ◽

Bone Substitute ◽

Guided Bone Regeneration ◽

Cranial Bone ◽

Collagen Membrane ◽

Defect Model

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Guided bone regeneration in staged vertical and horizontal bone augmentation using platelet-rich fibrin associated with bone grafts: a retrospective clinical study

International Journal of Implant Dentistry ◽

10.1186/s40729-020-00266-y ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Carlos Alberto Amaral Valladão ◽

Mabelle Freitas Monteiro ◽

Julio Cesar Joly

Keyword(s):

Bone Regeneration ◽

Bone Grafts ◽

Bone Defects ◽

Guided Bone Regeneration ◽

Collagen Membrane ◽

Bone Augmentation ◽

Platelet Rich Fibrin ◽

Link Type ◽

Retrospective Clinical Study ◽

Bone Gain

Abstract Background The use of guided bone regeneration (GBR) for vertical and horizontal bone gain is a predictable approach to correct the bone defects before implant installation; however, the use of different protocols is associated with different clinical results. It is suggested that platelet-rich fibrin (PRF) could improve the outcomes of regenerative procedures. Thus, this study aimed to describe the bone gain associated with GBR procedures combining membranes, bone grafts, and PRF for vertical and horizontal bone augmentation. Materials and methods Eighteen patients who needed vertical or horizontal bone regeneration before installing dental implants were included in the study. The horizontal bone defects were treated with a GBR protocol that includes the use of a mixture of particulate autogenous and xenogenous grafts in the proportion of 1:1, injectable form of PRF (i-PRF) to agglutinate the graft, an absorbable collagen membrane covering the regenerated region, and leukocyte PRF (L-PRF) membrane covering the GBR membrane. The vertical bone defects were treated with the same grafted mixture protected by a titanium-reinforced non-resorbable high-density polytetrafluoroethylene (d-PTFE-Ti) membrane and covered by L-PRF. The bone gain was measured using a cone-beam computed tomography at baseline and after a period of 7.5 (± 1.0) months. Results All patients underwent surgery to install implants after this regenerative protocol. The GBR produces an increase in bone thickness (p < 0.001) and height (p < 0.005) after treatment, with a bone gain of 5.9 ± 2.4 for horizontal defects and 5.6 ± 2.6 for vertical defects. In horizontal defects, the gain was higher in the maxilla than in mandible (p = 0.014) and in anterior than the posterior region (p = 0.033). No differences related to GBR location were observed in vertical defects (p > 0.05). Conclusion GBR associated with a mixture of particulate autogenous and xenogenous grafts and i-PRF is effective for vertical and horizontal bone augmentation in maxillary and mandibular regions, permitting sufficient bone gain to future implant placement. Trial registration REBEC, RBR-3CSG3J. Date of registration—19 July 2019, retrospectively registered. http://www.ensaiosclinicos.gov.br/rg/RBR-3csg3j/

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Demineralized Freeze-Dried Bovine Cortical Bone: Its Potential for Guided Bone Regeneration Membrane

International Journal of Dentistry ◽

10.1155/2017/5149675 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

David B. Kamadjaja ◽

Achmad Harijadi ◽

Pratiwi Soesilawati ◽

Eny Wahyuni ◽

Nurul Maulidah ◽

...

Keyword(s):

Immune Response ◽

Bone Regeneration ◽

Cortical Bone ◽

Guided Bone Regeneration ◽

Tissue Response ◽

Bone Collagen ◽

Cross Linking ◽

Collagen Membrane ◽

Tissue Integration ◽

Freeze Dried

Background. Bovine pericardium collagen membrane (BPCM) had been widely used in guided bone regeneration (GBR) whose manufacturing process usually required chemical cross-linking to prolong its biodegradation. However, cross-linking of collagen fibrils was associated with poorer tissue integration and delayed vascular invasion. Objective. This study evaluated the potential of bovine cortical bone collagen membrane for GBR by evaluating its antigenicity potential, cytotoxicity, immune and tissue response, and biodegradation behaviors. Material and Methods. Antigenicity potential of demineralized freeze-dried bovine cortical bone membrane (DFDBCBM) was done with histology-based anticellularity evaluation, while cytotoxicity was analyzed using MTT Assay. Evaluation of immune response, tissue response, and biodegradation was done by randomly implanting DFDBCBM and BPCM in rat’s subcutaneous dorsum. Samples were collected at 2, 5, and 7 days and 7, 14, 21, and 28 days for biocompatibility and tissue response-biodegradation study, respectively. Result. DFDBCBM, histologically, showed no retained cells; however, it showed some level of in vitro cytotoxicity. In vivo study exhibited increased immune response to DFDBCBM in early healing phase; however, normal tissue response and degradation rate were observed up to 4 weeks after DFDBCBM implantation. Conclusion. Demineralized freeze-dried bovine cortical bone membrane showed potential for clinical application; however, it needs to be optimized in its biocompatibility to fulfill all requirements for GBR membrane.

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Guided bone regeneration of non-contained mandibular buccal bone defects using deproteinized bovine bone mineral and a collagen membrane: an experimental in vivo investigation

Clinical Oral Implants Research ◽

10.1111/clr.13014 ◽

2017 ◽

Vol 28 (11) ◽

pp. 1466-1476 ◽

Cited By ~ 6

Author(s):

Mariano Sanz ◽

Luca Ferrantino ◽

Fabio Vignoletti ◽

Massimo de Sanctis ◽

Tord Berglundh

Keyword(s):

Bone Regeneration ◽

Bone Mineral ◽

Bone Defects ◽

Guided Bone Regeneration ◽

Collagen Membrane ◽

Bovine Bone ◽

Bovine Bone Mineral ◽

Deproteinized Bovine Bone Mineral ◽

Deproteinized Bovine Bone

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A Synthetic Biodegradable Polymer Membrane for Guided Bone Regeneration in Bone Defect

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3044 ◽

2021 ◽

Vol 17 (3) ◽

pp. 456-465

Author(s):

Kangjie Ma ◽

Dongmei Mei ◽

Xiaodong Lin ◽

Li Zhang ◽

Jie Gao ◽

...

Keyword(s):

Mechanical Strength ◽

Bone Regeneration ◽

Polylactic Acid ◽

Bone Defect ◽

Biodegradable Polymer ◽

Alveolar Bone ◽

Guided Bone Regeneration ◽

Collagen Membrane ◽

Gbr Membrane ◽

Alveolar Bone Defect

Guided bone regeneration (GBR) technique is most commonly used to treat alveolar bone defect. Polylactic acid (PLA) attracts much attention to utilize as a GBR membrane because it has relatively high mechanical strength and biodegradability. However, randomized controlled trials of PLA as a GBR membrane in animals were rare. The aim of this work is to observe the efficacy of polylactic acid membrane in guiding bone regeneration in Beagle canine alveolar bone defect restoration and to compare efficacy with the collagen membrane, providing an experimental basis for further clinical use of the polylactic acid membrane. The tests of physical and chemical properties showed that the PLA membrane has well mechanical strength to maintenance the space for the new bone, and has proper aperture for the attachment of osteoblasts. Through X-ray and histopathological examination of the different time points, the bone grafting material covered with PLA membrane can form similar mature bone compared to collagen membrane ones. Meanwhile, biodegradable speed of the PLA membrane was slower. Thus, this study showed that polylactic acid membrane as synthetic biodegradable polymer was reliably effective in guiding bone regeneration of alveolar bone defects, showed the favorable osteogenic capability and forecasts well applications in bone augmentation.

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