Zelus, E. I. | bioRxiv Science

bioRxiv2026

An Improved Manufacturing Method for Infusible Extracellular Matrix Materials to Enable Efficient Scale-Up, Improved Efficacy, and Clinical Translation

Decellularized extracellular matrix (ECM) materials are a popular choice for tissue engineering and regenerative medicine applications due to their multifaceted bioactive capabilities arising from their heterogenous composition. For minimally invasive delivery, infusible ECM (iECM) was developed through fractionation of digested decellularized ECM, allowing the material to be safely delivered intravascularly. iECM localizes to permeable vasculature in inflamed tissues and exerts immunomodulatory and pro-reparative effects with proof-of-concept already demonstrated in multiple preclinical models including myocardial infarction (MI) and multiple organ dysfunction syndrome (MODS). However, one major limitation of iECM is the steps required for manufacturing, involving centrifugation, dialysis/lyophilization, and filtration (C-D-F). These steps limit manufacturing output and iECM concentration, and require significant human handling, limiting compliance with current good manufacturing practices (cGMP). To overcome these challenges, we developed a method for manufacturing iECM that utilizes depth filtration and tangential flow filtration (DF-TFF), which reduces manufacturing time, allows for increased iECM concentration, and reduces human manipulation of material, improving translatability and scalability of iECM materials. Based on multiple material characterization methods, we determined that iECM made with DF-TFF was comparable to iECM made with C-D-F. By increasing iECM concentration through this manufacturing method, we demonstrate a dose dependent response in an acute MI porcine model and a mouse MODS model. Finally, DF-TFF enabled timely production of iECM from alternative tissue sources. Altogether, DF-TFF allows for improvements in production time, scale-up, cGMP compliance, and increased dose through higher concentration, paving the way for future clinical translation as well new preclinical studies.

bioengineering↗

bioRxiv2022

Immunomodulatory Extracellular Matrix Hydrogel Mitigates Scar Formation in a Model of Tongue Fibrosis.

BackgroundWhile head and neck cancer treatment regimens, including surgical resection, irradiation, and chemotherapy, are effective at removing tumors, they lead to muscle atrophy, denervation, and fibrosis, contributing to the pathogenesis of tongue dysphagia - difficulty swallowing. Current standard of care is ineffective; we propose an alternative approach utilizing an acellular and minimally invasive biomaterial to preserve muscle content and reduce fibrosis of the tongue after injury. Here, we investigate a decellularized extracellular matrix hydrogel for the treatment of tongue fibrosis in a partial glossectomy injury model. MethodsSkeletal muscle extracellular matrix (SKM) hydrogel was fabricated by decellularizing porcine skeletal muscle tissue through established protocols. A partial glossectomy injury in the rat was used as a model of tongue fibrois, and SKM hydrogels along with saline controls were injected to the site of scarring two weeks after injury. Tissues were harvested at 3 and 7 days post-injection for gene expression analysis of immune and myogenic pathways, and at 4 weeks post-injection to evaluate histomorphological changes in skeletal muscle and scar formation. ResultsSKM hydrogel reduced scar formation and improved muscle fiber cross-sectional area in the region of injury compared to saline controls. SKM upregulated pro-regenerative immune response while downregulating pro-inflammatory response and further promoted angiogenic gene expression. ConclusionThis study demonstrates the immunomodulatory and tissue-regenerative capacity of an acellular and minimally invasive biomaterial in a rodent model of tongue fibrosis.

bioengineering↗