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.

Enhanced angiogenesis by the hyaluronic acid hydrogels immobilized with a VEGF mimetic peptide in a traumatic brain injury model in rats

Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of developing brain extracellular matrix,hyaluronic acid(HA)has attracted more attention as a supporting matrix for brain repair.In the present study,HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT(KLTWQELYQLKYKGI).The characterization of the hydrogel shows that it could provide a porous,three-dimensional scaffold structure,which has a large specific surface area available for cell adhesion and interaction.Compared with the unmodified HA hydrogel,the HA-KLT hydrogel could effectively promote the attachment,spreading and proliferation of endothelial cells in vitro.Furthermore,the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain.Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation.Moreover,they could efficiently inhibit the formation of glial scars at the injured sites.The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels,suggesting that HA-KLT hydrogel promoted angiogenesis in vivo.Collectively,the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.

Gene expression profiling and mechanism study of neural stem cells response to surface chemistry

To declare the mechanisms of neural stem cells(NSCs)in response to material surface chemistry,NSCs were exposed to the self-assemble monolayers of alkanethiolates on gold surfaces terminated with amine(NH2),hydroxyl(OH)and methyl(CH3)for analysis.The morphological responses of NSCs were recorded;the gene expression profilings were detected by genechips;the gene expressions data of NSCs responded to different chemical groups were declared through the gene ontology term and pathway analyses.It showed that cells behaved dissimilar on the three chemical groups,the adhesion,proliferation and migration were easier on the NH2 and OH groups;the gene expressions of NSCs were induced differently,either,involved in several functional processes and signaling pathways.CH3 group induced genes enriched much in chemistry reactions and death processes,whereas many genes of cellular nucleotide metabolism were down-regulated.NH2 group induced NSCs to express many genes of receptors on membrane,and participated in cellular signal transduction of cell adhesion and interactions,or associated with axon growth.OH group was similar to NH2 group to induce the membrane response,but it also down regulated metabolism of cells.Therefore,it declared the chemical groups affected NSCs through inner way and the NH2,OH and CH3 groups triggered the cellular gene expression in different signaling pathways.

Modified poly(methyl methacrylate) bone cement in the treatment of Kümmell disease

Kuümmell disease(KD)causes serious vertebral body collapse in patients.However,only a few case reports have been conducted and the number of patients with KD investigated was limited.Additionally,the frequently used poly(methyl methacrylate)(PMMA)bone cement for KD is limited by excessive modulus and poor biocompatibility.Herein,we aimed to modify PMMA bone cement with mineralized collagen(MC),and compare the clinical effects,image performance and finite ele-ment analysis between the modified bone cement and PMMA bone cement for the treatment of phase I and II KD.Thirty-nine KD patients treated with PMMA bone cement and 40 KD patients treated with MC-modified PMMA bone cement from June 2015 to March 2017 were retrospectively analyzed.The surgical procedure,intraoperative blood loss,hospital stay and complications were compared between different groups.Visual analog scale,Oswestry disability index,anterior verte-bral height,posterior vertebral height,computed tomography value,adjacent vertebral re-fracture,Cobb angle and wedge-shaped correction angle were evaluated.Additionally,the representative sample was selected for finite element analysis.We found that the MC-modified PMMA bone ce-ment could achieve the same effect as that of PMMA bone cement and was associated with better vertebral height restoration in the long term.

Two competitive nucleation mechanisms of calcium carbonate biomineralization in response to surface functionality in low calcium ion concentration solution

Four self-assembled monolayer surfaces terminated with–COOH,–OH,–NH_(2)and–CH_(3)functional groups are used to direct the biomineralization processes of calcium carbonate(CaCO_(3))in low Ca^(2+)concentration,and the mechanism of nucleation and initial crystallization within 12 h was further explored.On-COOH surface,nucleation occurs mainly via ion aggregation mechanism while prenucleation ions clusters may be also involved.On-OH and-NH_(2)surfaces,however,nucleation forms via calcium carbonate clusters,which aggregate in solution and then are adsorbed onto surfaces following with nucleation of amorphous calcium carbonate(ACC).Furthermore,strongly negative-charged-COOH surface facilitates the direct formation of calcites,and the-OH and-NH_(2)surfaces determine the formation of vaterites with preferred crystalline orientations.Neither ACC nor crystalline CaCO_(3)is observed on-CH_(3)surface.Our findings present a valuable model to understand the CaCO_(3)biomineralization pathway in natural system where functional groups composition plays a determining role during calcium carbonate crystallization.

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.

Repairing skull defects in children with nano-hap/collagen composites: A clinical report of thirteen cases

Objective:To evaluate the clinical results of repairing skull defects with biomimetic bone(nano-hap/collagen composites,NHACs)in children.Methods:Thirteen children with skull defects were treated with NHACs in our hospital.The NHACs molded with the help of a 3D printer were used in the operations.Results:All 13 operations were successful,and patients recovered without infection.Only one patient suffered from subcutaneous hydrops post-operation.The implanted NHACs remained fixed well after 1 year,and their CT HU values raised gradually.Skull shapes of children developed normally.Recovery of neurological and cognitive function was significant.Conclusions:NHAC,chosen to repair skull defects in children,can coexist with normal skull and reduce the negative effects on growth and development.NHAC could be a good choice for children with skull defects.

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.

Mediating Mesenchymal Stem Cells Responses and Osteopontin Adsorption via Oligo(ethylene glycol)-amino Mixed Self-assembled Monolayers

Oligo（ethylene glycol） （-OEG） and amino （-NH2） mixed self-assembled monolayers （SAMs） were employed as model substrates to investigate the effect of charge density on the fate of mesenchymal stem cells （MSCs） and osteopontin （OPN） adsorption. We found that all surfaces presenting -NH2 groups favored cell responses regardless of the surface charge. Meanwhile, OPN adsorption could remain stable on the mixed SAMs over a certain range of charge densities. Our work provides some insights into cell responses and protein adsorption to surface charge.