Collagen Membrane for Guided Cortical Bone Regeneration: Characterization, Preclinical and Proof of Concept Clinical Studies
Authors: Allan Brent , Ruan Rui , Landao-Bassonga Euphemie , Gillman Nicholas , Wang Tao , Gao Junjie , Ruan Yonghua , Xu Yuan , Goonewardene Mithran , Lee Clair , Zheng Minghao 
Published: May 2020

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