Research On Ectopic Bone Formation Of Porous Scaffolds With Complementary Pore Structures In Vivo And Bio-functionalization Of Cobalt-Chromium Alloy

As the development of modern society and people’s living standard, the requirements to biomedical materials, especially the implantable biomedical materials, are beconing higher and higher, moreover these implant materials with single component and structure have not been satisfy the complex demands in clinical applications. On the one hand, in the field of bone-tissue engineering, the high positivity and connectivity of porous scaffolds, which are favourable for tissue ingrowth, cell migration, nutrients exchange and vascularization, are considered to be the key factors of materials organizational reconstruction, osteoconduction and osteoinduction in vivo. Although the relationship between pore structure and ectopic bone formation of porous scaffolds recieved widespread attention, it has not yet been revealed. On the other hand, the drug eluting stent (DES), due to the polymeric stents cannot control the drug sustained release for a long time, as well as the single surface properties and lack of biological activity of Co-Cr alloy, the desire that to form a bio-functional coating on Co-Cr alloy surface to serve as a bioactive drug reservoir become increasingly strong. Thus, the relationship on pore structure and ectopic bone formation in porous scaffolds was researched by constructing complementary and connected pore structure. Simultaneously, the surface properties of Co-Cr alloy was improved by biomimetic drug immobilization method.In this study, two types of hydroxyapatite (HA) scaffolds with complementary macro-pore structure were fabricated via spherulites-accumulating and porogen-preparing, and then implanted at non-osseous site of canines, the dorsal muscle, to reveal the relationship between complementary pore structures and ectopic bone formation. The histological results showed that excellent interconnectivity of both scaffolds is beneficial to tissue ingrowth. After1month implantation, denser calcium deposition layer was found in spherulite-porogen scaffolds, indicating that these scaffolds own better tissue-materials active interface in early implanted stage. Specifically, in the HA spherulite-accumulating scaffolds, new bone tissues were located after3months implantation, rather than in the spherulite-porogen scaffolds. And the mechanical properties of spherulite-accumulating scaffolds are better than spherulite-porogen scaffolds. As a result of the convex arc pore structure in spherulite-accumulating scaffolds is more conductive to liquid flowing, protein adhesion and cell migration, the effect of organizational reconstruction in these scaffolds is better. The experimental results confirmed that scaffold pore structure have a major impact on ectopic bone formation.In addition, bioactive apatite coating was formed as a carrier to immobilize sirolimus on Co-Cr alloy surface by alkali-heat treatment and biomimetic mineralization, and this newly formed bio-functional layer can achieve the drug sustained and controlled release in drug-eluting system. Firstly, after acid etching and alkali-heat treatment, the alloy surface became uniform and beneficial for apatite crystal nucleation and growth. Secondly, a calcium phosphate coating firmly binded to substrate and sirolimus immobilization was obtained through biomimetic mineralization and drip method, respectively. The sirolimus immobilized by above processes can release at least90days in phosphate buffer solution (PBS), which improved the performance of DES.