溫感水膠製備多孔性生物陶瓷複合藥物奈米載體於骨癒合之研究

組織工程目前已被證明是為最有前途的骨缺損治療方法之一[1]。為了能促進生物體內的藥物傳遞系統與骨修復效果，因此對於支架來說必須與其機械性質達到相對的平衡[1]。根據研究指出，在體內實驗時，由氫氧基磷灰石與三鈣磷酸鹽所組成之支架能促進新骨生成的表現[2]。有關研究也指出，含有孔洞直徑80~160μm[3]或500~1000μm[4]的多孔性生物陶瓷能夠加速使血管結締組織與骨骼向內生長。由氫氧基磷灰石所製備出的多孔性陶瓷其機械強度須以文獻指出的海綿骨機械強度(~5MPa)為基準[5]。目前許多技術皆可以有效製備出多孔性陶瓷，雖然這些方法與技術可以有效調控孔徑大小與孔隙的相互連結以及所需的幾何形狀，但是往往因其機械強度過低而難應用。另一方面，statins藥物能有效的在肝臟部位抑制膽固醇合成，文獻也指出不論是在大鼠或兔子體內實驗中也確實能誘導新骨的生成，但需注意的是在高濃度下的statins會引發橫紋肌溶血症[6]。在此研究中將提出一種新穎的技術，利用溫感型水膠技術與成孔劑法製備出具有高機械強度與多孔性結構的氫氧基磷灰石與三鈣磷酸鹽為主的陶瓷。希望藉由溫度的升高而使粉體因溫感水膠的收縮使之更緊實進而燒結以達到高機械強度的效果。此外將在多孔性陶瓷上乘載促骨化藥物simvastatin，以期對於骨治癒能達到加成化治療效果

關鍵字

氫氧基磷灰石；辛代他汀

並列摘要

Tissue engineering has proved to be one of the most promising therapies for bone fracture defects [1]. This new paradigm requires scaffolds that balance temporary mechanical function with mass transport to aid biological delivery and bone repair [1]. It has been reported that of HAp/TCP (hydroxyapatite/tricalcium phosphate) promotes the new bone formation from in vivo experiments [2]. While, porous bioceramic acts as a scaffold for the rapid ingrowths of vascularized connective tissue and bone. According to the current literature the optimal pore size is estimated to be 80~160 [3] or 500~1000 ?慆 [4]. Besides the strength acts the performance of porous hydroxyapatite ceramics. However, the compressive strength of cancellous bone will be ~5 MPa [5]. Several technologies exist today to manufacture strong and reliable porous ceramics. But these scaffolds prepared methods maybe can have a controllable pore size, interconnected pores, and desired geometry but often poor mechanical strength for load-bearing applications [5]. Besides, statins have potent compounds that inhibit cholesterol synthesis in the liver and have been reported to induce bone formation, both in tissue culture and in rats and mice [6, 7]. However, the high concentration of simvastatin have rhabdomyolysis side effect [6]. In this study, we report a novel technique that integrates the thermo-responsive hydrogel technique with porogen polymer method to prepare HAp/TCP porous scaffolds with improved mechanical strength and controllable porous structure. The hypothesis is that thermo-responsive hydrogel will shrink with the temperature increasing; then the function can be regarded as isostatic cold pressing (ICP) effect before ceramic sintering. Meanwhile, we filled appropriate simvastatin in porous bioceramic to obtain optimal release profile.