Guided bone regeneration in long-bone defect with a bilayer mineralized collagen membrane

Bone regeneration for large,critical-sized bone defects remains a clinical challenge nowadays.Guided bone regeneration(GBR)is a promising technique for the repair of multiple bone defects,which is widely used in oral and maxillofacial bone defects but is still unsatisfied in the treatment of long bone defects.Here,we successfully fabricated a bilayer mineralized collagen/collagen(MC/Col)-GBR membrane with excellent osteoinductive and barrier function by coating the MC particles prepared via in situ biomimetic mineralization process on one side of a sheet-like pure collagen layer.The aim of the present study was to investigate the physicochemical properties and biological functions of the MC/Col film,and to further evaluate its bone regeneration efficiency in large bone defect repair.Fouriertransform infrared spectra and X-ray diffraction patterns confirmed the presence of both hydroxyapatite and collagen phase in the MC/Col film,as well as the chemical interaction between them.stereo microscope,scanning electron microscopy and atomic force microscope showed the uniform distribution of MC particles in the MC/Col film,resulting in a rougher surface compared to the pure Col film.The quantitative analysis of surface contact angle,light transmittance and tensile strength demonstrated that the MC/Col film have better hydrophilicity,mechanical properties,light-barrier properties,respectively.In vitro macrophage co-culture experiments showed that the MC/Col film can effectively inhibit macrophage proliferation and fusion,reducing fibrous capsule formation.In vivo bone repair assessment of a rabbit critical segmental radial defect proved that the MC/Col film performed better than other groups in promoting bone repair and regeneration due to their unique dual osteoinductive/barrier function.These findings provided evidence that MC/Col film has a great clinical potential for effective bone defect repair.

Construction of a mineralized collagen nerve conduit for peripheral nerve injury repair

A new nerve guidance conduits(NGCs)named MC@Col containing Type I collagen(Col)and mineralized collagen(MC)was developed,enhancing mechanical and degradation behavior.The physicochemical properties,the mechanical properties and in vitro degradation behavior were all evaluated.The adhesion and proliferation of Schwann cells(SCs)were observed.In the in vivo experiment,MC@Col NGC and other conduits including Col,chitosan(CST)and polycaprolactone(PCL)conduit were implanted to repair a 10-mm-long Sprague-Dawley rat’s sciatic nerve defect.Histological analyses,morphological analyses,electrophysiological analyses and further gait analyses were all evaluated after implantation in 12 weeks.The strength and degradation performance of the MC@Col NGC were improved by the addition of MC in comparison with pure Col NGC.In vitro cytocompatibility evaluation revealed that the SCs had good viability,attachment and proliferation in the MC@Col.In in vivo results,the regenerative outcomes of MC@Col NGC were close to those by an autologous nerve graft in some respects,but superior to those by Col,CST and PCL conduits.The MC@Col NGC exhibited good mechanical performance as well as biocompatibility to bridge nerve gap and guide nerve regeneration,thus showing great promising potential as a new type of conduit in clinical applications.

A high-strength mineralized collagen bone scaffold for large-sized cranial bone defect repair in sheep

Large-sized cranial bone defect repair presents a great challenge in the clinic.The ideal cranioplasty materials to realize the functional and cosmetic recovery of the defect must have sufficient mechanical support,excellent biocompatibility,good osseointegration and biodegradability as well.In this study,a high-strength mineralized collagen(MC)bone scaffold was developed with biomimetic composition,microstructure and mechanical properties for the repair of sheep largesized cranial bone defects in comparison with two traditional cranioplasty materials,polymethyl methacrylate and titanium mesh.The compact MC scaffold showed no distinct pore structure and therefore possessed good mechanical properties.The strength and elastic modulus of the scaffold were much higher than those of natural cancellous bone and slightly lower than those of natural compact bone.In vitro cytocompatibility evaluation revealed that the human bone marrow mesenchymal stem cells(hBMSC)had good viability,attachment and proliferation on the compact MC scaffold indicating its excellent biocompatibility.An adult sheep cranial bone defect model was constructed to evaluate the performances of these cranioplasty materials in repairing the cranial bone defects.The results were investigated by gross observation,computed tomography scanning as well as histological assessments.The in vivo evaluations indicated that compact MC scaffold showed notable osteoconductivity and osseointegration with surrounding cranial bone tissues by promoting bone regeneration.Our results suggested that the compact MC scaffold has a promising potential for large-sized cranial bone defect repair.

Biphasic mineralized collagen-based composite scaffold for cranial bone regeneration in developing sheep

Appropriate mechanical support and excellent osteogenic capability are two essential prerequisites of customized implants for regenerating large-sized cranial bone defect.Although porous bone scaffolds have been widely proven to promote bone regeneration,their weak mechanical properties limit the clinical applications in cranioplasty.Herein,we applied two previously developed mineralized collagen-based bone scaffolds(MC),porous MC(pMC)and compact MC(cMC)to construct a biphasic MC composite bone scaffold(bMC)to repair the large-sized cranial bone defect in developing sheep.A supporting frame composed of cMC phase in the shape of tic–tac–toe structure was fabricated first and then embedded in pMC phase.The two phases had good interfacial bond,attributing to the formation of an interfacial zone.The in vivo performance of the bMC scaffold was evaluated by using a cranial bone defect model in 1-month-old sheep.The computed tomography imaging,X-ray scanning and histological evaluation showed that the pMC phase in the bMC scaffold,similar to the pMC scaffold,was gradually replaced by the regenerative bone tissues with comprehensively increased bone mineral density and complete connection of bone bridge in the whole region.The cMC frame promoted new bone formation beneath the frame without obvious degradation,thus providing appropriate mechanical protection and ensuring the structural integrity of the implant.In general,the sheep with bMC implantation exhibited the best status of survival,growth and the repair effect.The biphasic structural design may be a prospective strategy for developing new generation of cranioplasty materials to regenerate cranial bone defect in clinic.

A new method to standardize CBCT for quantitative evaluation of alveolar ridge preservation in the mandible:a case report and review of the literature

Cone-beam computerized tomography(CBCT)is an effective technique for assessment of changes to the alveolar ridge(AR).However,its accuracy and reliability could be improved by standardization of imaging positions to remain unchanged during measurements.In this study,an alveolar ridge preservation procedure was performed on a left third molar(38)socket by filling it with a radiotransparent synthetic bone graft,mineralized collagen(MC).Photographic,X-ray and CBCT images were captured before and 3,6 and 12 months after surgery.A new method was developed to standardize CBCT for quantitative evaluation.Obtained CBCT images showed good comparability.The post-extraction alveolar width and height were both over 95%of the original values,but some resorption of the lingual bone wall(>50%)and inter-crestal bone(>30%).It is concluded that an effective positional standardization method was developed for CBCT assessment of AR dimensional changes in the posterior mandible.The use of MC in combination with a collagen membrane improved dimensional preservation of the AR.

Biodegradable mineralized collagen plug for the reconstruction of craniotomy burr‐holes:A report of three cases

Objectives: In this case report, we describe the design, fabrication and clinical outcomes of a novel bioresorbable, mineralized collagen burr‐hole plug for the reconstruction of craniotomy burr‐holes. Methods: Mineralized collagen burr‐hole plugs were fabricated via a biomimetic mineralization process. The biomimetic mineralized collagen has a similar chemical composition and microstructure to natural bone tissue, thereby possessing good biocompatibility and osteoconductivity. The mineralized collagen burr‐hole plugs were implanted into three patients, and clinical outcomes were evaluated at one‐year follow‐ups. Results: All bone defects healed very well using the mineralized collagen burr‐hole plugs, and there were no adverse reactions at the surgical sites. Conclusions: The clinical outcomes indicated that the mineralized collagen was effective for reconstructing burr‐holes in the skull after craniotomy.

Skull repair materials applied in cranioplasty: History and progress

The skull provides protection and mechanical support, and acts as a container for the brain and its accessory organs. Some defects in the skull can fatally threaten human life.Many efforts have been taken to repair defects in the skull, among which cranioplasty is the most prominent technique. To repair the injury, numerous natural and artificial materials have been adopted by neurosurgeons. Many cranioprostheses have been tried in the past decades, from autoplast to bioceramics. Neurosurgeons have been evaluating their advantages and shortages through clinical practice. Among those prostheses, surgeons gradually prefer bionic ones due to their marvelous osteoconductivity,osteoinductivity, biocompatibility, and biodegradability. Autogeneic bone has been widely recognized as the "gold standard" for renovating large-sized bone defects. However, the access to this technique is restricted by limited availability and complications associated with its use. Many metal and polymeric materials with mechanical characteristics analogous to natural bones were consequently applied to cranioplasty. But most of them were unsatisfactory concerning osteoconductiion and biodegradability owe to their intrinsic properties. With the microstructures almost identical to natural bones, mineralized collagen has biological performance nearly identical to autogeneic bone, such as osteoconduction. Implants made of mineralized collagen can integrate themselves into the newly formed bones through a process called "creeping substitution". In this review, the authors retrospect the evolution of skull repair material applied in cranioplasty. The ultimate skull repair material should have microstructure and bioactive qualities that enable osteogenesis induction and intramembranous ossification.