Optimization of Enzymatic and Chemical Decellularization of Native Porcine Heart Valves for the Generation of Decellularized Xenografts

去细胞化 免疫原性 心脏瓣膜 细胞外基质 生物相容性 组织工程 生物医学工程 化学 胶原酶 细胞生物学 超微结构 解剖 免疫系统 生物化学 生物 医学 免疫学 外科 有机化学
作者
Monireh Saeid Nia,Lena Maria Floder,Jette Seiler,Thomas Puehler,Nina Sophie Pommert,Rouven Berndt,David Meier,Stephanie Sellers,Janarthanan Sathananthan,Xiling Zhang,Mario Hasler,Stanislav N. Gorb,G. Warnecke,Georg Lutter
出处
期刊:International Journal of Molecular Sciences [MDPI AG]
卷期号:25 (7): 4026-4026 被引量:3
标识
DOI:10.3390/ijms25074026
摘要

One of the most important medical interventions for individuals with heart valvular disease is heart valve replacement, which is not without substantial challenges, particularly for pediatric patients. Due to their biological properties and biocompatibility, natural tissue-originated scaffolds derived from human or animal sources are one type of scaffold that is widely used in tissue engineering. However, they are known for their high potential for immunogenicity. Being free of cells and genetic material, decellularized xenografts, consequently, have low immunogenicity and, thus, are expected to be tolerated by the recipient's immune system. The scaffold ultrastructure and ECM composition can be affected by cell removal agents. Therefore, applying an appropriate method that preserves intact the structure of the ECM plays a critical role in the final result. So far, there has not been an effective decellularization technique that preserves the integrity of the heart valve's ultrastructure while securing the least amount of genetic material left. This study demonstrates a new protocol with untraceable cells and residual DNA, thereby maximally reducing any chance of immunogenicity. The mechanical and biochemical properties of the ECM resemble those of native heart valves. Results from this study strongly indicate that different critical factors, such as ionic detergent omission, the substitution of Triton X-100 with Tergitol, and using a lower concentration of trypsin and a higher concentration of DNase and RNase, play a significant role in maintaining intact the ultrastructure and function of the ECM.

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