近年來組織工程的快速發展為再生組織或器官開創了許多可能性，而及時的在工程組織裡血管化是組織再生成功的重要關鍵，如何在短時間內產生厚的血管化組織，進而增進組織存活率與功能性發展，是目前組織工程最需要被解決的問題。隨著製造技術的進步，已有許多圖案化水凝膠策略在體外實驗取得重大的進展，然而多數研究缺乏體內實驗數據，使圖案化策略在體內的效用與機制依然並不明確。
我們比較了生物3D列印與微影製程在圖案化明膠甲基丙烯(Gelatin methacrylate, GelMA)水凝膠中的優勢與限制，微影製程展現了顯著較佳的細胞活性與結構穩定性。透過對微影製程的改良，可以輕易製造出厚1 mm的可堆疊圖案化GelMA水凝膠，而透過曝光時間的調控，能夠在50 %、70 %和100 %覆蓋率水凝膠中建立相同的材料性質，且圖案化水凝膠顯示更快的降解速率與擴散效率。在體外培養中，圖案化水凝膠可以克服細胞培養的厚度限制、增進細胞的行為表現並擴大適合細胞生長的材料特性範圍。
在體內動物實驗方面，以圖案化GelMA水凝膠結合人類間質幹細胞(Mesenchymal stem cell, MSC)和人臍靜脈內皮細胞(Human umbilical vein endothelial cell, HUVEC)共培養策略，使用裸鼠皮下植入模型證明若是給予適當的空間(70 %覆蓋率)且在體內保持3D結構(w/ spacer)，圖案化結構可以有效增進細胞反應並引導血管生成，7天內在厚的水凝膠(2 mm)內部形成均勻的血管網路；在裸鼠全層皮膚傷口癒合模型中，也證實圖案化GelMA水凝膠可以增進傷口前期血管新生與肉芽形成能力，在一個月內高度回復皮膚功能化附屬物與機械性質，促進無疤痕皮膚再生。

Rapid progress of tissue engineering in recent years has opened up tremendous possibilities for regenerating tissues. Timely vascularization into engineered tissue plays a critical role in the success of tissue regeneration, but how to rapidly construct thicker vascularized tissue, thereby improving tissue survivability and functional development, is the problem most needed to be solved in tissue engineering. With the advancement of manufacturing technology, numerous strategies of patterned hydrogels have made significant progress in vitro, whereas most studies lacked of in vivo animal experimental results. The effects and mechanisms of the patterning strategies in vivo remained unclear.
We compared the advantages and limitations of 3D bioprinting and lithography process in forming patterned Gelatin methacrylate (GelMA) hydrogels. The lithography process demonstrated better cell viability and structural stability. Through the improvement of the lithography process, the stackable patterned GelMA hydrogel with 1 mm thickness can be easily fabricated. The same material properties could be established in 50 %, 70 % and 100 % coverage GelMA hydrogels by adjusting exposure times, and the patterned hydrogels showed faster degradation rate and diffusion efficiency compared to unpatterned 100 % coverage GelMA ones. In vitro cell culture, patterned GelMA hydrogels were able to overcome the thickness limitations in cell culture to enhance cell behavior and expand the range of suitable material properties for cell growth.
In vivo animal experiments, the patterned GelMA hydrogels were combined with human mesenchymal stem cell (MSC) and human umbilical vein endothelial cell (HUVEC) co-culture strategy. Using nude mice subcutaneous implantation model proved that if the appropriate space (70 % coverage) was given and the 3D structure (w/ spacer) was maintained in vivo, the patterned structure could enhance cellular response and guide angiogenesis to form a uniform vascular network in the thick hydrogel (2 mm) within 7 days. In the full-thickness skin wound healing model of nude mice, it was also confirmed that the patterned GelMA hydrogels were able to enhance the angiogenesis and granulation formation in the early stage of the wound healing, and high restoration of the skin functional appendages and mechanical properties were oberserved within 1 month to promote the scarless skin regeneration.

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