Asthana Amish, Gallego Amanda, Perrier Quentin, Lozano Tamara, Byers Lori N, Ho-Heo Jun, Jeong Wonwoo, Tamburrini Riccardo, Rengaraj Arunkumar, Chaimov Deborah, Tomei Alice, Fraker Christopher A, Lee Sang Jin, Orlando Giuseppe
Department of Surgery, Wake Forest Baptist Medical Center, Medical Center Boulevard, Winston-Salem, NC, United States.
Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, United States.
Front Bioeng Biotechnol. 2025 Apr 25;13:1518665. doi: 10.3389/fbioe.2025.1518665. eCollection 2025.
The importance of the extracellular matrix (ECM) to pancreatic islets has been clearly demonstrated, as isolated islets grown in culture or transplanted, quickly lose viability and function after their matrix associations have been stripped away during the isolation process. Therefore, recapitulating the islet niche is a critical objective to move the field of islet transplantation forward.
As a first step to recreating the islet microenvironment, we have recently developed a detergent-free decellularization method to obtain a decellularized solubilized ECM (dsECM) powder from human pancreas. We have also shown that this gentler method (compared to traditional detergent-based methods) allows for thorough preservation of the molecular fingerprint of the innate organ. Furthermore, incorporation of dsECM in alginate-microencapsulated human islets, showed a significant increase in insulin secretion, compared to both free and alginate-only encapsulated islets. However, it is also essential to test the interaction of dsECM with multiple cell types to establish its safety for transplantation.
Herein, we present a comprehensive evaluation of the cytotoxicity, hemocompatibility and immunocompatibility of dsECM to establish a concentration range where it deemed safe and biocompatible. Furthermore, dsECM-based bioinks were coaxially bioprinted and the resulting construct's biocompatibility and vascularization potential were also evaluated .
细胞外基质（ECM）对胰岛的重要性已得到明确证明，因为在培养中生长或移植的分离胰岛，在分离过程中其与基质的联系被去除后，会迅速丧失活力和功能。因此，重现胰岛微环境是推动胰岛移植领域发展的关键目标。
作为重建胰岛微环境的第一步，我们最近开发了一种无洗涤剂的脱细胞方法，以从人胰腺中获得脱细胞溶解的细胞外基质（dsECM）粉末。我们还表明，这种更温和的方法（与传统的基于洗涤剂的方法相比）能够彻底保留天然器官的分子指纹。此外，与游离和仅用藻酸盐包封的胰岛相比，将dsECM掺入藻酸盐微囊化的人胰岛中，胰岛素分泌显著增加。然而，测试dsECM与多种细胞类型的相互作用以确定其移植安全性也至关重要。
在此，我们对dsECM的细胞毒性、血液相容性和免疫相容性进行了全面评估，以确定其被认为安全且生物相容的浓度范围。此外，基于dsECM的生物墨水被同轴生物打印，并对所得构建体的生物相容性和血管生成潜力进行了评估。
