Development of an Anisotropic Collagen-Apatite Composite Scaffold and Application for Bone Tissue Engineering(II)

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Project title

Code/計畫編號

MOST108-2221-E019-029-MY2

Translated Name/計畫中文名

異向性膠原蛋白-磷灰石複合支架之開發及其在骨組織工程上的應用(II)

Project Coordinator/計畫主持人

Fu-Yin Hsu

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Department of Bioscience and Biotechnology

Website

https://www.grb.gov.tw/search/planDetail?id=13329020

Year

2020

Start date/計畫起

01-08-2020

Expected Completion/計畫迄

31-07-2021

Bugetid/研究經費

1055千元

ResearchField/研究領域

醫學工程

骨組織的成分主要是由生物磷灰石與膠原蛋白所構成。合成的氫氧基磷灰石由於化學性質、生物特性與骨組織內的生物磷灰石組成相似，使氫氧基磷灰石擁有良好的生物相容性、生物活性與骨引導特性，而被廣泛使用作為骨填補材料、細胞載體與藥物或基因的載體。此外，鍶置換型氫氧基磷灰石具有降解性且可促進間葉幹細胞骨生成作用，並可抑制間葉幹細胞脂肪生成作用。因此鍶置換型氫氧基磷灰石有潛力成為在骨再生中的骨填補物。另外一方面，由於細胞的增生與分化會與細胞於基質上的貼附行為習習相關。而基材的表面型態、組成及力學特性都會影響到細胞的貼附、細胞的伸展、遷移、增生、基因表現、細胞膜表面之抗原表現及細胞骨架等細胞行為。利用電紡技術所製備之高分子或是高分子-生醫陶瓷複合奈米纖維已被證實可促進骨母細胞的分化。此外，骨母細胞培養在順向性高分子或是高分子-生醫陶瓷複合奈米纖維上具有更好的成骨性相較於培養在無順向性之奈米纖維。計畫主持人過去所執行科技部之研究計畫已成功的利用電氣紡織技術製備生醫陶瓷奈米纖維基質(如氫氧基磷灰石奈米纖維、鍶置換型氫氧基磷灰石奈米纖維、生物活性玻璃奈米纖維等)，且發現生醫陶瓷奈米纖維基質可促進骨母細胞的分化。然而，至目前為止並無任何文獻探討順向性生醫陶瓷奈米纖維基質對骨母細胞及蝕骨細胞的影響。因此，研究計劃的第一年，我們將著重在具順向性結構之孔洞型氫氧基磷灰石奈米纖維基質(pHA-ANF)及順向性結構之孔洞型鍶置換氫氧基磷灰石奈米纖維基質(pSrHA-ANF)之製備，並評估pHA-ANF和pSrHA-ANF之藥物釋放特性、體外降解性、體外生物活性及對類骨母細胞及類蝕骨細胞的影響。骨組織結構的異向性是來自於膠原蛋白纖維和磷灰石晶體共同形成有方向性排列而產生。因此，研究計劃的第二年我們將使用pHA-ANF或pSrHA-ANF來製備具異向性特性之膠原蛋白-磷灰石複合支架，並探討異向性膠原蛋白-磷灰石複合支架之力學特性及對骨母細胞之細胞行為的影響。最後並以動物實驗來驗證異向性膠原蛋白-磷灰石複合支架對骨再生的影響。 Natural bone tissue is primarily composed of bioapatite and collagen. Synthetic hydroxyapatite (Ca10(PO4)6(OH)2, HA) possesses good biocompatibility, bioactivity, and osteoconductivity due to its chemical and biological similarity to the bioapatite. Hence, HA has been widely used as bone graft, cell carrier and drug/gene delivery carrier. Moreover, strontium-substituted hydroxyapatite (SrHA) could enhance osteogenic differentiation and inhibit adipogeneic differentiation of mesenchymal stem cell. Hence SrHA has the potential to be used as bone graft for bone regeneration. It is widely accepted that cell adhesion and most cellular activities, including spreading, migration, proliferation, gene expression, surface antigen display and cytoskeletal function, are sensitive to the topography and molecular composition of the matrix. Electrospun polymer or polymer-bioceramic composite nanofibers had been demonstrated could enhance differentiation of osteoblasts. Moreover, aligned polymer or polymer-bioceramic composite nanofibers showed the better osteogenesis of osteoblasts than random nanofibers. At the previous MOST projects, we had successfully set up an electrospinning system to fabricate a nanofibrous bioceramic matrix (such as mesoporous hydroxyapatite, mesoporous strontium-substituted hydroxyapatite and mesoporous bioactive glass nanofiber), and also found the nanofibrous bioceramic matrix could enhance differentiation of osteoblasts. However, up to date, there are no literatures to investigate the effect of aligned nanofibrous bioceramic matrix on osteoblasts and osteoclasts. Therefore, at the first year, the major works of this project will fabricate aligned nanofibrous matrix of mesoporous hydroxyapatite (pHA-ANF) and aligned nanofibrous matrix of mesoporous strontium-substituted hydroxyapatite (pSrHA-ANF), and investigate drug release property, the in vitro degradation, and cellular response of osteoblasts and osteoclasts on pHA-ANF and pSrHA-ANF matrix. The characteristic anisotropic architecture of bone tissue derived from the coordinated alignment of collagen fibers and apatite crystals. Therefore, the major works of this project at 2nd year, we will use pHA-ANF or pSrHA-ANF to fabricate an anisotropic collagen-apatite composite scaffold containing aligned collagen fibers and aligned apatite fibrous matrix, and to evaluate the effects of this anisotropic collagen-apatite composite scaffold on mechanical properties and cellular behaviors of osteoblasts. Finally, we will evaluate the performance of anisotropic collagen-apatite composite scaffold on bone regeneration.

Keyword(s)

鍶
氫氧基磷灰石
膠原蛋白
電氣紡織
異向性
複合支架
骨再生
strontium
hydroxyapatite
collagen
electrospin
anisotropic
composite scaffold
bone regeneration

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Development of an Anisotropic Collagen-Apatite Composite Scaffold and Application for Bone Tissue Engineering(II)

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