Critical Size Bone Defect Healing Using Collagen–Calcium Phosphate Bone Graft Materials

Walsh, William R.; Oliver, Rema A.; Christou, Chris; Lovric, Vedran; Walsh, Emma Rose; Prado, Gustavo R.; Haider, Thomas

doi:10.1371/journal.pone.0168883

Cited by 60 publications

(56 citation statements)

References 61 publications

(61 reference statements)

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“…Typically, defects are created in a weight-bearing region of the sheep bone, which provides similarities in bone composition, defect size and healing rate compared to humans 36,38 . Critical defects models generally evaluate the in vivo performance of biomaterials in terms of bone regeneration, remodelling, biomaterial resorption and biological effects 35,39,40 .…”

Section: Introductionmentioning

confidence: 99%

Full-Field Strain Analysis of Bone–Biomaterial Systems Produced by the Implantation of Osteoregenerative Biomaterials in an Ovine Model

Fernández

Dall’Ara

Bodey

et al. 2019

ACS Biomater. Sci. Eng.

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Osteoregenerative biomaterials for the treatment of bone defects are under much development, with the aim of favoring osteointegration up to complete bone regeneration. A detailed investigation of bone–biomaterial integration is vital to understand and predict the ability of such materials to promote bone formation, preventing further bone damage and supporting load-bearing regions. This study aims to characterize the ex vivo micromechanics and microdamage evolution of bone–biomaterial systems at the tissue level, combining high-resolution synchrotron microcomputed tomography, in situ mechanics and digital volume correlation. Results showed that the main microfailure events were localized close to or within the newly formed bone tissue, in proximity to the bone–biomaterial interface. The apparent nominal compressive load applied to the composite structures resulted in a complex loading scenario, mainly due to the higher heterogeneity but also to the different biomaterial degradation mechanisms. The full-field strain distribution allowed characterization of microdamage initiation and progression. The findings reported in this study provide a deeper insight into bone–biomaterial integration and micromechanics in relation to the osteoregeneration achieved in vivo for a variety of biomaterials. This could ultimately be used to improve bone tissue regeneration strategies.

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Section: Introductionmentioning

confidence: 99%

Full-Field Strain Analysis of Bone–Biomaterial Systems Produced by the Implantation of Osteoregenerative Biomaterials in an Ovine Model

Fernández

Dall’Ara

Bodey

et al. 2019

ACS Biomater. Sci. Eng.

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“…While the in vitro characterisation of CelGro™ showed that CelGro™ contains relatively pure type I collagen bundles and display less deformity and better mechanical strength, we next conducted a preclinical study to determine the efficacy of CelGro ™ for GBR in the repair of diaphysis cortical bones defects in rabbits. Previously, it has been shown that healing of a standard-sized defect in rabbit femoral bone treated with bone autograft occurs between 30 to 60 days after surgery (22) (23). To evaluate the efficacy of collagen membranes in conjunction At 30 days after surgery, the effect of a collagen membrane could be clearly observed by micro-CT (Fig.…”

Section: Regeneration Of Cortical Bone Defects In a Rabbit Modelmentioning

confidence: 99%

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

Allan

Ruan

Landao-Bassonga

et al. 2020

Preprint

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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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“…Ex vivo evaluation of bone regeneration is conducted at one unique time point and it usually involves histology, SEM and XCT investigations (Coathup et al, 2008;Wang et al, 2015;Machado et al, 2016;Walsh et al, 2017;. The three techniques are complimentary and combined provide a deep insight on bone formation in the defect site.…”

Section: Ex Vivo Analysis Of Bone Regenerationmentioning

confidence: 99%

“…On the other hand, cranial-defect models lack from weight-bearing and, therefore, their clinical relevance may be questioned due to the absence of loading that can affect the potential bone formation capacity of the biomaterials (Cowan et al, 2004;Pound et al, 2006;Bolland et al, 2008;Dawson et al, 2008;Kisiel et al, 2013). Large animal models, such as femoral condyle-defect models in rabbits or sheep circumvent some of that shortcomings, as defects are created in a weight-bearing region and no fixators are needed (Walsh et al, 2003;Fini et al, 2005;Ueng et al, 2007;Malhotra et al, 2014;Pobloth et al, 2016;Walsh et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Applications of X‐ray computed tomography for the evaluation of biomaterial‐mediated bone regeneration in critical‐sized defects

Fernández

Witte²,

Tozzi

2019

Journal of Microscopy

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Bone as such displays an intrinsic regenerative potential following fracture; however, this capacity is limited with large bone defects that cannot heal spontaneously. The management of critical‐sized bone defects remains a major clinical and socioeconomic need with osteoregenerative biomaterials constantly under development aiming at promoting and enhancing bone healing. X‐ray computed tomography (XCT) has become a standard and essential tool for quantifying structure–function relationships in bone and biomaterials, facilitating the development of novel bone tissue engineering strategies. This paper presents recent advancements in XCT analysis of biomaterial‐mediated bone regeneration. As a noninvasive and nondestructive technique, XCT allows for qualitative and quantitative evaluation of three‐dimensional (3D) scaffolds and biomaterial microarchitecture, bone growth into the scaffold as well as the 3D characterisation of biomaterial degradation and bone regeneration in vitro and in vivo. Furthermore, in combination with in situ mechanical testing and digital volume correlation (DVC), XCT demonstrated its potential to better understand the bone–biomaterial interactions and local mechanics of bone regeneration during the healing process in relation to the regeneration achieved in vivo, which will likely provide valuable knowledge for the development and optimisation of novel osteoregenerative biomaterials. Lay Description Bone, being a dynamically adaptable material, displays excellent regenerative properties following fracture. However, the self‐healing capacity of bone becomes more difficult with large bone defects. Those defects are common and occur in many clinical situations; hence, biomaterials are mostly used to restore both bone structure and function in the defect site. X‐ray computed tomography (XCT) is a powerful tool to evaluate bone regeneration in critical‐sized defects after the implantation of biomaterials, allowing to an improved understanding of the regeneration process following different bone tissue engineering approaches. This paper focuses on recent advancements in XCT analysis to characterise biomaterial‐mediated bone regeneration in critical‐sized defects. XCT supports three‐dimensional (3D) analysis of biomaterials, scaffolds and regenerated bone microarchitecture, as well as bone ingrowth into the scaffold. As a nondestructive technique, XCT allows for a 3D characterisation of biomaterial degradation and bone regeneration over time. In addition, XCT combined with in situ mechanical experiments and digital volume correlation (DVC) provides a 3D evaluation and quantification of bone–biomaterial interactions and deformation mechanisms during the regeneration process. This remains essential for the development and enhancement of novel biomaterials able to produce bone that is comparable with the native tissue they aim to replace.

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Critical Size Bone Defect Healing Using Collagen–Calcium Phosphate Bone Graft Materials

Cited by 60 publications

References 61 publications

Full-Field Strain Analysis of Bone–Biomaterial Systems Produced by the Implantation of Osteoregenerative Biomaterials in an Ovine Model

Full-Field Strain Analysis of Bone–Biomaterial Systems Produced by the Implantation of Osteoregenerative Biomaterials in an Ovine Model

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

Applications of X‐ray computed tomography for the evaluation of biomaterial‐mediated bone regeneration in critical‐sized defects

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