Adenosine-treated bioprinted muscle constructs prolong cell survival and improve tissue formation

• 作者: Dongxu Ke Adam M.Jorgensen Sang J.Lee James J.Yoo Sean V.Murphy
• 来源期刊: 生物设计与制造（英文版）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: RESEARCH ARTICLES
• 页码范围: 441-451
• 页数: 11页
• 语种: 英文

摘要

It is crucial to maintaining the viability of biofabricated human-sized tissues to ensure their successful survival and function after transplantation. Adenosine is a purine nucleoside that has the function to suppress cellular metabolism and has been previously proposed as a method to prolong cell viability under hypoxia. In this study, we optimized the dose concentration of adenosine for incorporation into bioprinted constructs to preserve long-term cell viability in vitro. Our results showed that muscle cells (C2C12) containing 6, 7, or 8 mM adenosine maintained high cell viability for 20 days under hypoxic conditions (0.1％ O2), whereas cells without adenosine treatment showed 100％ cell death after 11 days. After 20 days under hypoxic conditions, muscle cells treated with adenosine proliferated and differentiated when transferred to normoxic conditions. From these adenosine concentrations, 6 mM was picked as the optimized adenosine concentration for further investigations due to its most effective results on improving cell viability. The bioprinted muscle constructs containing adenosine (6 mM) maintained high cell viability for 11 days under hypoxic conditions, while the control constructs without adenosine had no live cells. For in vivo validation, the bioprinted constructs with adenosine implanted under the dorsal subcutaneous space in mice, showed the enhanced formation of muscle tissue with minimal central necrosis and apoptosis, when compared to the constructs without adenosine. These positive in vitro and in vivo results demonstrate that the use of adenosine is an effective approach to preventing the challenge of hypoxia-induced necrosis in bioprinted tissues for clinical translation.