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.

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.

Mineralized collagen-modified PMMA cement enhances bone integration and reduces fibrous encapsulation in the treatment of lumbar degenerative disc disease

As a minimally invasive surgery,percutaneous cement discoplasty(PCD)is now contemplated to treat lumbar disc degeneration disease in elder population.Here,we investigated whether the osteogenic mineralized collagen(MC)modified polymethylmethacrylate(PMMA)cement could be a suitable material in PCD surgery.Injectability,hydrophilicity and mechanical properties of the MC-modified PMMA(PMMA-MC)was characterized.The introduction of MC did not change the application and setting time of PMMA and was easy to be handled in minimally invasive operation.Hydrophilicity of PMMA-MC was greatly improved and its elastic modulus was tailored to complement mechanical performance of bone under dynamic stress.Then,PCD surgery in a goat model with induced disc degeneration was performed with implantation of PMMA-MC or PMMA.Three months after implantation,micro-computed tomography analysis revealed a 36.4%higher circumferential contact index between PMMA-MC and bone,as compared to PMMA alone.Histological staining confirmed that the surface of PMMA-MC was in direct contact with new bone,while the PMMA was covered by fibrous tissue.The observed gathering of macrophages around the implant was suspected to be the cause of fibrous encapsulation.Therefore,the interactions of PMMA and PMMA-MC with macrophages were investigated in vitro.We discovered that the addition of MC could hinder the proliferation and fusion of the macrophages.Moreover,expressions of fibroblaststimulating growth factors,insulin-like growth factor,basic fibroblast growth factor and tumor necrosis factor-b were significantly down-regulated in the macrophages cocultured with PMMA-MC.Together,the promoted osteointegration and reduced fibrous tissue formation observed with PMMA-MC material makes it a promising candidate for PCD surgery.

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.

Histopathological and imageological studies on clinical outcomes of mineralized collagen reconstruction rod for femoral head necrosis with one case report

In this article,the biodegradation process and bone formation of a mineralized collagen reconstruction rod embedding in necrosis of human femoral head were investigated by imageological and histological methods.Computed radiography(CR)computerized tomography(CT),common pathological section and hard tissue section analysis were used to evaluated the dynamics of imageological and histopathological changes of femoral head,interface between the host bone and implant and the bone reconstruction process.The results showed that the density of rods increased closed to that of host bones after 1 year implanting,and the interface between them turns to blurring.Hard tissue grinding sections analysis showed osteocytes appearing in sparse bone trabecular and bone pit region,as well as a few vessels in the degraded dye powder matrix were noticed,indicating the new bone forming between the implants and host bones.Regular decalcified sections analysis showed scattered osteoclasts,multinucleated giant cells and fibrosis components existing in the degraded rod and the host bone trabecular.Degraded debris was endocytosed by giant cells,and vascular network formed around the boundaries of the implanted rod.The good osteointegration has been expressed by the interface between the implanted rod and the host bone becoming blurred.Histological results indicated that the implanted rod degradation process and new bones regeneration simultaneously occurred around the boundaries of embedding rod.New bone and host bone were hinged and co-existed.

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.

Biomechanical evaluation of different hydroxyapatite coatings on titanium for keratoprosthesis

Stable tissue integration is important to keratoprosthesis （KPro）. The aim of this study was to evaluate the tissue bonding ability of hydroxyapatite （HAp）-coated titanium KPro. The samples were divided into three groups： test groups （IBAD group and AD group） and Ti control. The coated samples had a HAp layer created by ion beam assisted deposition （IBAD） or aerosol deposition （AD）. The surface characteristics were analyzed with SEM, AFM, and XRD. The samples were surgically inserted into the muscles of rabbits. Eight weeks after healing, the attachment to the tissue was tested with a universal test device. The three samples exhibited distinctive surface morphology. The force to remove the HAp implants from the muscles was significantly greater than that of Ti group （P〈0.01）, with the AD samples requiring the greatest force （P〈0.01）. After removal, SEM showed that the tissue was firmly attached to the surface of AD samples. Photomicrographs of the peri-implant muscles showed a layer of aligned fibrous tissue without severe inflammation. The AD samples had more fibroblasts. Results indicate that because of enhanced mechanical adhesion of soft tissue to the implants, HAp-coated Ti by AD is a suitable KPro skirt material.