細胞外基質（ECM）由結構和功能大分子的複雜混合物組成，在組織和器官形態以及維持細胞和組織結構功能中起到重要的作用。而細胞外基質在生長，發育和傷口修復過程中扮演重要的角色，其自身的動態成分可充當訊號分子的儲存庫，並介導其他來源的訊號使細胞遷移、增殖及分化。在天然生物醫學材料中，細胞外基質來源於動物組織，將源自動物組織的細胞外基質植入生物體內後，它可以釋放信號來調節動態細胞行為（例如增殖，存活，粘附和遷移）的能力，並影響細胞的快速生長以促進傷口再生。但是，在提取ECM的過程中我們必須使組織脫細胞，從組織中去除細胞以避免宿主組織排斥植入的ECM支架。從組織或器官中去除細胞會留下構成ECM的結構蛋白和功能蛋白的複雜混合物。
本研究描述了一種結合物理和化學處理的脫細胞方法。
第一階段，我們通過化學處理使膀胱組織脫細胞，將其凍乾粉末化，並且測定化學殘留以及膠原蛋白濃度的含量。第二階段為將萃取之細胞外基質製備為ECM懸浮液。第三階段進行體外細胞分析，利用ECIS及細胞劃痕試驗評估細胞外基質於對傷口癒合的作用與反應、生物相容性。
研究結果顯示，該實驗成功地從組織中去除了細胞，並且萃取出每毫克含有0.6mg之細胞外基質，並且無化學殘留的跡象。儘管在DNA分析中脫細胞後ECM的DNA含量大於50 ng/mg，可能有必要改進脫細胞方法以避免動物實驗中的排斥效應。在體外細胞試驗中，無論是ECIS測試還是傷口癒合試驗，HaCaT在較高濃度的細胞外基質懸浮液當中，表現出細胞附著電極的速率和細胞遷移速率明顯增加，儘管細胞外基質懸浮液的濃度高於膠原蛋白，但由於目前膠原蛋白相當昂貴，使用我們提取的細胞外基質是一種經濟的解決方案，並且可以達到與膠原蛋白相同的效果。
經由一系列實驗，脫細胞的ECM已經證明了它們作為支架誘導傷口癒合機制的潛力。未來的研究應進一步改良脫細胞方案，以使DNA小於50 ng/mg，以防止可能在動物實驗中發生的排斥反應。

關鍵字：細胞外基質、組織工程、脫細胞化、生物相容性、再生醫學

The extracellular matrix (ECM) consists of a complex mixture of structural and functional macromolecules and serves an important role in tissue and organ morphogenesis and in the maintenance of cell and tissue structure and function. The extracellular matrix evolves an important role in the growth, development, and wound repair processes. Its own dynamic composition acts as a reservoir for soluble signaling molecules and mediates signals from other sources to migrating, proliferating, and differentiating cells. In natural biomedical materials, the extracellular matrix derived from animal tissues is implanted in living organisms, it can release signals to abilities to regulate dynamic cellular behaviors, such as proliferation, survival, adhesion and migration, to influence rapid growth of the cells and to promote wound regeneration. To avoid the host tissue's rejection of the implanted ECM scaffold, we must remove cells from the ECM scaffold by a series of decellularization process. The complex mixture of structural and functional proteins of the ECM were maintains after the decellularization process and can be used for many biomedical applications.
In this study, we described a decellularization method that combines physical and chemical treatments.
In the first step of this study, bladder tissue was decellularized by chemical and physical treatments, lyophilized and powdered, and the contents of chemical residues and collagen concentration were determined. The second step was to prepare the extracted extracellular matrix as an ECM suspension. In the third step, in vitro analysis was performed. ECIS and wound healing and migration assay were used to evaluate the effect and response of extracellular matrix on wound healing and biocompatibility.
The research results showed that most of the cells in ECM were successfully removed from the tissue by the DAPI staining method. However, we also found the DNA content of the ECM after decellularization process was greater than 50 ng/mg. In vitro experiments, whether its test of ECIS or wound healing, HaCaT cells show a significant increase in the rate of cell-electrode attachment and cell migration in higher concentrations of extracellular matrix suspension. Although the concentration of extracellular matrix suspensions was higher than collagen, due to the current collagen is quite expensive and using our extracellular matrix is an economical solution and can achieve the same effect as collagen.
Through a series of experiments, decellularized ECM has demonstrated their potential as scaffolds to induce mechanisms of wound healing. Future research should further improve the decellularization protocol to reduce the DNA level below 50 ng/mg to prevent immune response in the future animal experiment.

Keywords: Extracellular matrix, Tissue engineering, Decellularization, Biocompatibility, Regenerative medicine

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