由於關節軟骨其自我修復能力不足，軟骨修復方式是一大熱門研究主題，但目前臨床的相關手術方式仍存在一些缺點需要解決，因此科學家們提出組織工程來作為軟骨缺損修復的潛力療法，期望能製備可改善或恢復受損組織功能的仿生組織。在材料方面，根據先前研究指出經由硫醇鍵修飾的異丙基丙烯醯胺與幾丁聚醣共聚物水凝膠具有溫感性、可注射性、良好的生物相容性以及透過雙硫共價鍵交聯增強的機械性質，這些特性使其極有潛力作為軟骨修復應用的支架材料。
在大部分的研究中，骨軟骨缺損再生的評估通常於健康動物中進行，不過根據臨床調查指出關節軟骨缺損若無追蹤治療，未來可能演變成骨關節炎(OA)，另一調查亦指出骨軟骨缺損通常由嚴重的外力創傷和身體疾病(例如關節炎)引起，根據統計，到2012年美國約有3100萬人患有骨關節炎，其中有9.2%的病患具有骨軟骨缺損，因此骨軟骨缺損與骨關節炎之間具有強烈的關聯性。
在本研究中我們想評估硫醇鍵修飾的異丙基丙烯醯胺與幾丁聚醣共聚物水凝膠結合具軟骨分化潛力的人類脂肪間質幹細胞，在碘乙酸鈉(MIA)藥物誘導的骨關節炎兔子模型中的軟骨再生能力，並討論添加依那西普(一種TNF-α抑製劑)對結果的影響。
我們首先成功合成了硫醇鍵修飾的異丙基丙烯醯胺與幾丁聚醣共聚物水凝膠，透過熱掃描卡量計(DSC)證實其具有合適的低臨界溶液溫度(LCST)：約31℃，此特性使其成為一可注射型的生醫材料，注入後能於原缺損位置快速由液狀變為膠狀；掃描式電子顯微鏡(SEM)亦發現水膠內部具有多孔的微結構，可使細胞貼附以及養分輸送；由雙硫共價鍵交聯增強的機械性質則透過迴旋式流變分析儀(Rheometer)進行驗證，最後再以CCK8試劑組證實此水膠不具備細胞毒性，可用於後續的體內試驗。
我們採用碘乙酸鈉(MIA)藥物誘導的方式於兔子膝關節中建立骨關節炎模型，並透過組織學染色以及IL-1β、IL-6、TNF-α細胞因子檢測討論其與正常動物模型的區別。最後再於此動物模型中進行骨軟骨缺損修復能力評估，根據宏觀觀察、微電腦斷層掃描儀(micro-CT)以及組織學染色分析，我們發現與空缺損組相比，含間質幹細胞的水凝膠組別皆於軟骨修復能力上具有顯著提升，而添加依那西普的組別於四周時較其他組有良好的修復表現，於十二周時則無顯著差異。
根據先前描述的結果，我們成功以碘乙酸鈉(MIA)藥物誘導的方式建立骨關節炎模型，並認為硫醇鍵修飾之異丙基丙烯醯胺與幾丁聚醣共聚物水凝膠結合具軟骨分化潛力之幹細胞具有極佳的潛力應用於軟骨組織工程中，此研究亦證實其於骨關節炎環境仍能表現良好的軟骨修復能力。

The self-healing ability of cartilage tissue is limited so that the cartilage repair methods have been extensively studied for decades, yet, there are still some shortages and limitations needed to be resolved. Tissue engineering is an emerging research field, which is committed to the formation of biomimetic tissues that improve or restore the function of damaged tissues. For scaffold, the previous study reported that thiol-modified NIPPAm-g-chitosan hydrogel, with thermo-sensitive, injectable, good biocompatibility, and enhancing mechanical properties by disulfide covalent bond crosslinking, is considered a suitable scaffold for the application of cartilage repair.
In most studies, evaluations of osteochondral regenerative were usually performed in healthy animals. However, traumatic defects of articular cartilage may eventually result in osteoarthritis (OA) if patients are in delay of treatment. Another survey showed that osteochondral defects are usually caused by severe traumas and physical diseases such as OA. According to reports, by 2012, approximately 31 million Americans suffered from OA, of which 9.2% had osteochondral defects. There seems to be a strong relationship between cartilage defect and OA.
Therefore, in this study, we want to evaluate the effect of thiol-modified NIPAAm-g-chitosan (TNC) hydrogels containing human adipose-derived mesenchymal stem cells with or without etanercept, a TNF-α inhibitor, for cartilage regeneration in the monosodium iodoacetate (MIA)-induced OA rabbit model.
We first successfully synthesized TNC hydrogels with suitable lower critical solution temperature (LCST), at about 31℃, confirmed by DSC. And the porous interior microstructures were showed in SEM images. The enhancing mechanical properties were tested by rheometer. Finally, we used the CCK8 kit to confirm that there was non-cytotoxicity of this hydrogel for further in vivo analysis.
The OA rabbit models were established by MIA-induced rabbit knee joints, with verification of histology staining and cytokine detection of IL-1β, IL-6, and TNF-α, which were increasing in OA. And the evaluations of osteochondral regeneration were performed in these OA models. Macroscopic evaluations, micro-CT analysis, and histological and immunohistochemical staining results showed that compared with empty defect groups, the cell-seeded hydrogel groups improved the cartilage regeneration, and the etanercept effectively promoted osteochondral defects repair in the first 4 weeks.
Based on the previously described results, we have successfully established MIA-induced OA models and considered that the TNC hydrogels containing chondrogenic potential stem cells could be expected for cartilage tissue engineering, which was also proven in OA models of this study.

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