氧氣在細胞調節、細胞增殖及能量產生上都扮演著重要的角色，若缺乏氧氣使細胞處於缺氧狀態，就容易因細胞代謝遭受破壞、ATP耗盡等現象，刺激細胞在短時間內死亡，導致組織壞死，產氧材料在臨床上是被廣泛需要的，像是骨折因常伴隨著血管結構的破壞，使得局部組織缺氧，進而導致骨折癒合不良或不癒合的情形。氧氣在骨折癒合中扮演重要的角色．其涉及了成骨細胞的分化、骨細胞增殖及骨礦化等等。為了改善細胞缺氧情形，並將其運用致臨床上，本論文開發一產氧載體，以聚乳酸-乙醇酸(poly latic-co-glycotic acid, PLGA)包覆過氧化鈣(CaO2)及二氧化錳(MnO2)。當PLGA降解時，水會滲透進入載體中和CaO2反應產生過氧化氫(H2O2)，並進一步被MnO2催化產生氧氣。實驗結果顯示，我們能夠以微流道系統製備出PLGA產氧微粒載體。將載體的各項參數最佳化後，該產氧微粒可使低氧環境下磷酸緩衝溶液中的溶氧量顯著上升，且最多可持續四天。在細胞實驗方面，我們也證實此PLGA產氧微粒載體不具有明顯細胞毒性。缺氧誘導因子的免疫螢光染色結果顯示，本論文開發之PLGA產氧微粒載體可提供足夠氧氣，使低氧(1% O2)培養環境中的細胞不致有明顯的缺氧情形發生。未來我們亦擬將此氧氣載體做更廣泛的應用，以了解本論文開發之氧氣載體在臨床上的潛能。

As a crucial molecule to life, oxygen is required in several cellular processes, such as aerobic respiration, enzyme activation, cell differentiation, collagen synthesis, that are involved in fracture healing. Therefore, a major hurdle in promoting bone regeneration is to provide sufficient oxygen to support the survival and function of the newly formed tissue. In this work, a composite oxygen-generating system consisting calcium peroxide (CaO2)/manganese dioxide (MnO2)-encapsulated poly lactic-co-glycolic acid (PLGA) microparticles (MPs) was developed for improving local oxygenation and preventing hypoxia-induced cell death. Once exposed to water, solid CaO2 particles embedded in the PLGA MPs can generate hydrogen peroxide (H2O2), which can be further converted into oxygen under the catalysis of MnO2. According to our results, the developed oxygen-generating MPs could produce oxygen continuously for four days without dramatic change in pH or accumulation of H2O2. The results of in vitro studies demonstrated that the oxygen-producing MPs could effectively relieve cellular hypoxia, suggesting their great potential for enhancing local oxygenation of the hypoxic tissues.

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