Biochemical and immunomodulatory insights of extracellular matrix from decellularized human whole cervix: recellularization andin vivoECM remodeling interplay.

Extracellular matrix (ECM) rich whole organ bio-scaffolds, preserving structural integrity and essential growth factors, has potential towards regeneration and reconstruction. Women with cervical anomalies or trauma can benefit from clinical cervicovaginal repair using constructs rich in site specific ECM. In this study, complete human cervix decellularization was achieved using a modified perfusion-based stir bench top decellularization method. This was followed by physico-chemical processes including perfusion of ionic agents, enzymatic treatment and washing using detergent solutions for a duration of 10-12 d. Histopathological analysis, as well as DNA quantification confirmed the efficacy of the decellularization process. Tissue ultrastructure integrity was preserved and the same was validated via scanning electron microscopy and transmission electron microscopy studies. Biochemical analysis and structural characterizations like Fourier transform infrared, Raman spectroscopy of decellularized tissues demonstrated preservation of important proteins, crucial growth factors, collagen, and glycosaminoglycans.In vitrostudies, using THP-1 and human umbilical vein endothelial cell (HUVEC) cells, demonstrated macrophage polarization from M1 to M2 and vascular functional genes enhancement, respectively, when treated with decellularized human cervical matrix (DHCp). Crosslinked DHC scaffolds were recellularized with site specific human cervical epithelial cells and HUVEC, showing non-cytotoxic cell viability and enhanced proliferation. Furthermore, DHC scaffolds showed immunomodulatory effectsin vivoon small rodent model via upregulation of M2 macrophage genes as compared to decellularized rat cervix matrix scaffolds (DRC). DHC scaffolds underwent neo-vascularization followed by ECM remodeling with enhanced tissue integration.

Human placenta/umbilical cord derivatives in regenerative medicine - Prospects and challenges.

The human placenta and umbilical cord, natural birth biowaste, are a housing unit for numerous bioactive macromolecules, growth factors, collagen and GAGs, with an array of high-quality stem cells. MSCs isolated from the human placenta and umbilical cord are utilized in both research and medical applications due to their sustainable sourcing, high viability, multipotent lineage and potency. They present an unprecedented opportunity in the tissue engineering, biomedical and biotechnology fields with minimal ethical constraints and nominal cost. Considering the world population and daily birth rates, with appropriate utilization and management, they could resolve the MSC shortage in the global stem cell therapy market and present biomedical waste disposal. A considerable number of clinical trials are presently underway where placenta-derived stem cells have been administered for different pathologies. Since the umbilical cord and placenta's primary function is to sustain the fetus until delivery, it has an ample supply of nutrients, proteins and essential factors necessary to assist cell viability and proliferation. Present research and medical applications include the fabrication of ECM-based nanofibers, disease models, micro-tissue, hybrid models and artificial implants. Future utilization of birthing biomedical waste in medical engineering and research will provide a rich and sustainable source of stem cells and extracellular matrix for enhanced biocompatibility and regeneration.