Elgin Shani, Silberman Eric, Shapira Assaf, Dvir Tal
The Shmunis School of Biomedicine and Cancer Research, Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
The Sagol Center for Regenerative Biotechnology, Tel Aviv University, Tel Aviv 6997801, Israel.
Gels. 2024 Aug 5;10(8):515. doi: 10.3390/gels10080515.
Overcoming the oxygen diffusion limit of approximately 200 µm remains one of the most significant and intractable challenges to be overcome in tissue engineering. The fabrication of hydrogel microtissues and their assembly into larger structures may provide a solution, though these constructs are not without their own drawbacks; namely, these hydrogels are rapidly degraded in vivo, and cells delivered via microtissues are quickly expelled from the area of action. Here, we report the development of an easily customized protocol for creating a protective, biocompatible hydrogel barrier around microtissues. We show that calcium carbonate nanoparticles embedded within an ECM-based microtissue diffuse outwards and, when then exposed to a solution of alginate, can be used to generate a coated layer around the tissue. We further show that this technique can be fine-tuned by adjusting numerous parameters, granting us full control over the thickness of the hydrogel coating layer. The microtissues' protective hydrogel functioned as hypothesized in both in vitro and in vivo testing by preventing the cells inside the tissue from escaping and protecting the microdroplets against external degradation. This technology may provide microtissues with customized properties for use as sources of regenerative therapies.
克服约200微米的氧扩散限制仍然是组织工程中要克服的最重大且棘手的挑战之一。水凝胶微组织的制造及其组装成更大的结构可能提供一种解决方案，不过这些构建体也有自身的缺点；也就是说，这些水凝胶在体内会迅速降解，并且通过微组织递送的细胞会很快从作用区域被排出。在此，我们报告了一种易于定制的方案的开发，用于在微组织周围创建保护性、生物相容性水凝胶屏障。我们表明，嵌入基于细胞外基质的微组织中的碳酸钙纳米颗粒会向外扩散，并且当暴露于藻酸盐溶液时，可用于在组织周围生成涂层。我们进一步表明，该技术可通过调整众多参数进行微调，使我们能够完全控制水凝胶涂层的厚度。微组织的保护性水凝胶在体外和体内测试中均如预期发挥作用，通过防止组织内的细胞逸出并保护微滴免受外部降解。这项技术可为微组织提供定制特性，用作再生疗法的来源。
