發(fā)布時(shí)間：2018-06-07 17:44

  本文選題：骨組織工程 + 生物礦化�。� 參考：《暨南大學(xué)》2017年碩士論文

【摘要】：近年來(lái),因先天性畸形、骨關(guān)節(jié)炎和意外事故中的創(chuàng)傷等原因所造成的骨缺損疾病患者數(shù)目日趨增多,其對(duì)骨組織工程移植材料的需求也隨之逐漸增加。骨組織工程支架材料作為骨缺損和骨損傷材料的載體一直以來(lái)都是骨組織工程的靈魂。因此,成功制備出一種具有骨傳導(dǎo)性和誘導(dǎo)性的理想型復(fù)合支架材料成為了修復(fù)骨缺損和骨損傷疾病的必要條件。根據(jù)天然骨的結(jié)構(gòu)和組成,以天然活性高分子為模板仿生生物礦化法合成的天然高分子/羥基磷灰石復(fù)合支架材料是本研究領(lǐng)域的熱點(diǎn)和核心。生物礦化方法能在一定程度上模擬出與天然骨具有相似形貌、尺寸和結(jié)晶度的磷灰石,并使復(fù)合支架材料達(dá)到良好的力學(xué)性能和生物活性。本論文在查閱了大量文獻(xiàn)和結(jié)合課題組本身的研究基礎(chǔ)上,選取了膠原(Collagen,COL)和殼聚糖(Chitosan,CS)兩種天然生物活性高分子作為有機(jī)模板,利用透析法仿生礦化調(diào)控羥基磷灰石無(wú)機(jī)礦物在有機(jī)基質(zhì)支架材料中的原位生成,制備出具有三維多孔結(jié)構(gòu)和優(yōu)異性能的有機(jī)-無(wú)機(jī)復(fù)合骨組織修復(fù)材料;也進(jìn)一步研究比較了生物礦化體系中兩種不同大分子有機(jī)模板對(duì)納米羥基磷灰石(n-HAP)調(diào)控的差別,并在不添加生長(zhǎng)因子和種子細(xì)胞的情況下,n-HAP/COL復(fù)合支架材料用于大鼠的背部皮下異位成骨實(shí)驗(yàn)的研究;nHAP/CS復(fù)合支架材料用于新西蘭兔股骨缺損修復(fù)的研究,從而間接對(duì)比兩種復(fù)合支架對(duì)骨再生和修復(fù)的情況。本論文通過(guò)選用不同的大分子有機(jī)基質(zhì)模板,借助于XRD、FTIR、TEM、SEM、TG/DTG、孔隙率和壓縮強(qiáng)度等測(cè)試的表征,研究了三維多孔支架材料的組成成分、結(jié)構(gòu)、孔隙度、生物相容性和力學(xué)性能的變化;并將n-HAP/COL復(fù)合支架材料用于體內(nèi)礦化實(shí)驗(yàn)和大鼠的背部皮下異位成骨實(shí)驗(yàn)的研究;而將n-HAP/CS復(fù)合支架材料用于MC-3T3成骨細(xì)胞的培養(yǎng)和新西蘭兔后腿股骨缺損修復(fù)實(shí)驗(yàn)的研究。結(jié)果表明:兩種復(fù)合支架材料表面和內(nèi)部孔洞中都有豐富的鈣磷鹽的沉積且這些鈣磷鹽都為納米級(jí)的羥基磷灰石,復(fù)合支架具有相互連通的孔隙結(jié)構(gòu)和很好的力學(xué)強(qiáng)度,陳化72h的n-HAP/COL的孔隙率為72.78?0.23%,壓縮強(qiáng)度和壓縮模量分別為230.23?0.81kPa和465?0.9kPa;而透析72h的n-HAP/CS的孔隙率為96.7?1.0%,壓縮強(qiáng)度和壓縮模量分別為0.44?0.01MPa和0.20?0.01MPa。n-HAP/COL復(fù)合支架材料在體內(nèi)研究初步證明了COL+Ca-GP組體內(nèi)礦化的可行性,但COL+Ca-GP+體外ALP組無(wú)異位成骨能力;而n-HAP/CS復(fù)合支架材料在動(dòng)物體內(nèi)骨缺損研究表明與純CS支架材料相比,n-HAP/CS復(fù)合支架材料更加能夠完美地促進(jìn)骨缺損的修復(fù),在植入體內(nèi)12周后,經(jīng)Micro-CT和組織形態(tài)學(xué)染色觀察證明n-HAP/CS實(shí)驗(yàn)組骨缺損修復(fù)基本完成。另外n-HAP/COL和n-HAP/CS兩種復(fù)合支架材料在體內(nèi)都具有良好組織相容性。
[Abstract]:In recent years, the number of patients with bone defects caused by congenital malformation, osteoarthritis and accidents is increasing, and the demand for bone tissue engineering transplantation has gradually increased. Bone tissue engineering scaffold material has always been bone tissue engineering as a carrier of bone defect and bone damage material. Therefore, the successful preparation of an ideal composite scaffold with bone conductivity and inducibility has become a necessary condition for the repair of bone defect and bone damage. Based on the structure and composition of natural bone, natural polymer / hydroxyapatite composite scaffold materials are synthesized by natural active polymer as template biomimetic biomineralization. The biomineralization method can simulate the apatite with similar morphology, size and crystallinity with the natural bone to a certain extent, and make the composite scaffold material achieve good mechanical properties and biological activity. This paper has been selected on the basis of a large number of literature and the research of the project group itself. Two kinds of natural bioactive polymers (Collagen, COL) and chitosan (Chitosan, CS) are used as organic templates to regulate the in-situ formation of hydroxyapatite inorganic minerals in organic matrix scaffold materials by dialytic biomimetic mineralization, and the organic and inorganic composite bone tissue repair materials with three-dimensional porous structure and excellent properties are prepared. Further studies and comparison of the differences in the regulation of nano hydroxyapatite (n-HAP) by two different macromolecular organic templates in the biomineralization system, and the study of the n-HAP/COL composite scaffold material used for ectopic osteogenesis in the back of rats without adding growth factors and seed cells; the nHAP/CS composite scaffold material was used in the new West. The study of the repair of the femur defect of the blue rabbit, in order to indirectly compare the situation of the bone regeneration and repair of the two composite scaffolds. In this paper, the composition, structure and pore of the three-dimensional porous scaffold are studied by using different macromolecule organic matrix templates and using the characterization of XRD, FTIR, TEM, SEM, TG/DTG, porosity and compression strength. The changes in degree, biocompatibility and mechanical properties; and the study of n-HAP/COL composite scaffold materials in vivo mineralization experiment and rat's back subcutaneous ectopic osteogenesis experiment. The n-HAP/CS composite scaffold materials were used in the culture of MC-3T3 osteoblasts and the study of the repair of the hind leg femur of New Zealand rabbits. The results showed that two kinds of composite scaffolds were used. There are abundant calcium and phosphorus salts deposited on the surface of the scaffold and the inner holes, and these calcium and phosphorus salts are nanometer hydroxyapatite. The composite scaffold has interconnected pore structure and good mechanical strength. The porosity of the n-HAP/COL of aging 72h is 72.78? 0.23%, the compressive strength and the compression modulus are 230.23? 0.81kPa and 465? 0.9 respectively. KPa, while the porosity of n-HAP/CS for dialysis 72h was 96.7? 1%, compression strength and compression modulus were 0.44? 0.01MPa and 0.20? 0.01MPa.n-HAP/COL composite scaffolds in vivo preliminarily proved the feasibility of mineralization in group COL+Ca-GP, but COL+Ca-GP+ in vitro ALP group had no bone formation ability; and n-HAP/CS composite scaffold was in animal body. The study of bone defect showed that compared with the pure CS scaffold material, the n-HAP/CS composite scaffold could improve the repair of bone defect perfectly. After 12 weeks of implantation, the Micro-CT and histomorphological staining showed that the repair of bone defect was basically completed in the n-HAP/CS experimental group. In addition, the two composite scaffolds of n-HAP/COL and n-HAP/CS were in the body. All of them have good histocompatibility.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：TB324;R318.08

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