Hyaluronic acid oligosaccharide-collagen mineralized product and aligned nanofibers with enhanced vascularization properties in bone tissue engineering.

Considering the structural complexity of natural bone and the limitations of current treatment options, designing a biomimetic and functional tissue-engineered bone graft has been an urgent need for the replacement and regeneration of defected bone tissue. In light of the cell recruitment to the defect region, scaffold-guided bone tissue engineering has proven to be a viable strategy that is poised to deliver effective osseointegration and vascularization during bone remodeling. Herein, we provide an engineered bone scaffold based on aligned poly(lactic-co-glycolide) (PLGA) nanofibers incorporated with hyaluronic acid oligosaccharide-collagen mineralized microparticles (labeled oHA-Col/HAP) to guide the cell-specific orientation and osseointegration in bone healing. The aligned nanofibers were successfully prepared by a custom-made rotating mandrel with separating railings and HAs-Col/HAP mineralized microparticles were uniformly distributed in the composite scaffolds that acted as temporary templates for bone remodeling. The morphology, physicochemical properties and tensile strength of the scaffolds were characterized, the cell responses and in vivo biocompatibility and biodegradability of the scaffolds were also studied to evaluate the potential for bone tissue engineering. The experimental results illustrated that such anisotropic scaffolds loaded with oHA-Col/HAP microparticles mediated cell orderly arrangement conducive to the migration and recruitment of osseointegration-related cells and were stimulatory of cell proliferation. Those oHA-Col/HAP@PLGA scaffolds exhibited ideal biocompatibility and tissue regenerative capacity in vivo through a higher expression of vascularization-related genes. Overall, the novel engineered bone scaffold promises to serve as alternative candidates for bone tissue engineering applications.

Mechanical strain induces the production of spheroid mineralized microparticles in the aortic valve through a RhoA/ROCK-dependent mechanism.

Calcific aortic valve disease (CAVD) is a chronic disorder characterized by an abnormal mineralization of the leaflets, which is accelerated in bicuspid aortic valve (BAV). It is suspected that mechanical strain may promote/enhance mineralization of the aortic valve. However, the effect of mechanical strain and the involved pathways during mineralization of the aortic valve remains largely unknown. Valve interstitial cells (VICs) were isolated and studied under strain conditions. Human bicuspid aortic valves were examined as a model relevant to increase mechanical strain. Cyclic strain increased mineralization of VICs by several-fold. Scanning electron microscope (SEM) and energy dispersive X-ray (EDX) analyses revealed that mechanical strain promoted the formation of mineralized spheroid microparticles, which coalesced into larger structure at the surface of apoptotic VICs. Apoptosis and mineralization were closely associated with expression of ENPP1. Inhibition of ENPP1 greatly reduced mineralization of VIC cultures. Through several lines of evidence we showed that mechanical strain promoted the export of ENPP1-containing vesicles to the plasma membrane through a RhoA/ROCK pathway. Studies conducted in human BAV revealed the presence of spheroid mineralized structures along with the expression of ENPP1 in areas of high mechanical strain. Mechanical strain promotes the production and accumulation of spheroid mineralized microparticles by VICs, which may represent one important underlying mechanism involved in aortic valve mineralization. RhoA/ROCK-mediated export of ENPP1 to the plasma membrane promotes strain-induced mineralization of VICs.