氫氧基磷灰石/聚乙二醇-聚己內酯之熔積成型支架及透明質酸水膠搭載轉化生長因子治療兔子軟硬骨缺陷

Fused Deposited Manufacturing of Hydroxyapatite-loaded PEG-PCL Scaffolds and TGF-β Loaded Glycidyl Hyaluronic Acids Hydrogel for The Treatment of Osteochondral Defects in Rabbits

方志翔(Chih-Hsiang Fang)

指導教授 ： 謝明發

中原大學/工學院/生物醫學工程研究所/碩士(2015年)

https://doi.org/10.6840/cycu201500713

摘要

退化性關節炎是年長者中常見的肌肉骨骼疾病，但目前尚未有有效的治療方式，利用組織工程促進組織再生是目前最具潛力之治療方式，然而，作為組織再生支架必須利於細胞長入，即支架之孔隙大小、型狀、連通性及對細胞之生物反應等，由於快速原型技術的出現，對於支架之設計及其特性可經由此技術達到控制，此外，透明質酸搭載生長因子，具有潛在能力維持軟骨細胞之特性。本研究目的在於利用熔積成型機台製備mPEG-PCL多孔支架，並利用RGD胜肽接枝於材料表面提升與細胞之相互作用，再搭配透明質酸搭載生長因子進行軟硬骨之修復。結果顯示，幹細胞與骨母細胞在經過RGD胜肽修飾過的材料表面有良好的貼附及增生，透過氫氧基磷灰石之添加，能夠提高支架其機械強度，降解測試顯示，經過3個月降解後，SEM可以觀察到材料其表面受到侵蝕，並且降低其抗壓強度及楊氏系數，在體外實驗中，幹細胞能在支架分化成軟骨細胞並長時間維持其功能表現，在動物實驗發現，植入支架與水膠包覆生長因子於缺陷處可以促使軟骨下硬骨之癒合及軟骨在生，同時，新生之軟骨組織為透明軟骨。

關鍵字

退化性關節炎,快速原型技術,組織工程,軟骨再生

並列摘要

Osteoarthritis, a musculoskeletal diseases prevailed in the elderly, there is no current threpy for curing osteoarthritis. Tissue engineering is the most protential way to heal the osteoarthritis, nevertheless, to promote the tissue regeneration by using tissue engineering was necessary. A scaffold of biomaterials for tissue regeneration which is well recognized that the internal architecture of the scaffold, namely pore size, shape and interconnectivity, has a strong effect on the biological response of the cells. Recently rapid prototyping has emerged to produce custom-made orthopedic implants having controlled internal architecture of scaffolds. In addition, hyaluronic acid hydrogel loading with transforming growth factor beta is potential to maintain the phenotypes of the chondrocytes in-vitro. The aims of this study, to use a home-made air pressure-assisted nozzle system to fabricate porous scaffolds of poly (ethylene glycol)-block-(ε-caprolactone), PEG-PCL. Then, modified with RGD peptide on the surface of the scaffold to enhance biological response of the cells.To regenerate the cartilage, HA hydrogel loaded with growth factor was filled into the pores of the rapid prototyping PEG-PCL scaffold as the mimicked extracellular matrix. Fluorescent staining of cytoskeleton of osteoblast-like and stem cells could well spread on RGD-modified PEG-PCL film indicating a favorable surface for rapid prototyping scaffolds. Yet the compressive strength of hydroxyapatite-doped rapid prototyping PEG-PCL scaffolds was enhanced as compared to pure PEG-PCL scaffolds. The degradation test of rapid prototyping scaffolds for a period of three months showed a characteristic surface erosion as indicated in the scanning electron microscopic images. After that the compressive strength and Young's modulus was decreased. For in-vitro test, stem cell could differentiate into chondrocytes and maintain their phenotype for long-term. In vivo test, rapid prototyping scaffolds and hydrogel with growth factor were implanted in osteochondral lesion. It was found that subcondral bone and cartilage were fully healed, the regenerated cartilage was hyaline cartilage.

並列關鍵字

Osteoarthritis,Rapid prototyping,Tissue engineering,Cartilage regeneration

參考文獻

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