Serum- and xeno-free culture of human umbilical cord perivascular cells for pediatric heart valve tissue engineering

Abstract Background Constructs currently used to repair or replace congenitally diseased pediatric heart valves lack a viable cell population capable of functional adaptation in situ, necessitating repeated surgical intervention. Heart valve tissue engineering (HVTE) can address these limitations by producing functional living tissue in vitro that holds the potential for somatic growth and remodelling upon implantation. However, clinical translation of HVTE strategies requires an appropriate source of autologous cells that can be non-invasively harvested from mesenchymal stem cell (MSC)-rich tissues and cultured under serum- and xeno-free conditions. To this end, we evaluated human umbilical cord perivascular cells (hUCPVCs) as a promising cell source for in vitro production of engineered heart valve tissue. Methods The proliferative, clonogenic, multilineage differentiation, and extracellular matrix (ECM) synthesis capacities of hUCPVCs were evaluated in a commercial serum- and xeno-free culture medium (StemMACS™) on tissue culture polystyrene and benchmarked to adult bone marrow-derived MSCs (BMMSCs). Additionally, the ECM synthesis potential of hUCPVCs was evaluated when cultured on polycarbonate polyurethane anisotropic electrospun scaffolds, a representative biomaterial for in vitro HVTE. Results hUCPVCs had greater proliferative and clonogenic potential than BMMSCs in StemMACS™ (p < 0.05), without differentiation to osteogenic and adipogenic phenotypes associated with valve pathology. Furthermore, hUCPVCs cultured with StemMACS™ on tissue culture plastic for 14 days synthesized significantly more total collagen, elastin, and sulphated glycosaminoglycans (p < 0.05), the ECM constituents of the native valve, than BMMSCs. Finally, hUCPVCs retained their ECM synthesizing capacity after 14 and 21 days in culture on anisotropic electrospun scaffolds. Conclusion Overall, our findings establish an in vitro culture platform that uses hUCPVCs as a readily-available and non-invasively sourced autologous cell population and a commercial serum- and xeno-free culture medium to increase the translational potential of future pediatric HVTE strategies. Graphical Abstract This study evaluated the proliferative, differentiation and extracellular matrix (ECM) synthesis capacities of human umbilical cord perivascular cells (hUCPVCs) when cultured in serum- and xeno-free media (SFM) against conventionally used bone marrow-derived MSCs (BMMSCs) and serum-containing media (SCM). Our findings support the use of hUCPVCs and SFM for in vitro heart valve tissue engineering (HVTE) of autologous pediatric valve tissue. Figure created with BioRender.com

Facile Method for Fabrication of Meter-Long Multifunctional Hydrogel Fibers with Controllable Biophysical and Biochemical Features

Contains fulltext : 218172.pdf (Publisher’s version ) (Closed access)Hydrogel structures with microscale morphological features have extensive application in tissue engineering owing to their capacity to induce desired cellular behavior. Herein, we describe a novel biofabrication method for fabrication of grooved solid and hollow hydrogel fibers with control over their cross-sectional shape, surface morphology, porosity, and material composition. These fibers were further configured into three-dimensional structures using textile technologies such as weaving, braiding, and embroidering methods. Additionally, the capacity of these fibers to integrate various biochemical and biophysical cues was shown via incorporating drug-loaded microspheres, conductive materials, and magnetic particles, extending their application to smart drug delivery, wearable or implantable medical devices, and soft robotics. The efficacy of the grooved fibers to induce cellular alignment was evaluated on various cell types including myoblasts, cardiomyocytes, cardiac fibroblasts, and glioma cells. In particular, these fibers were shown to induce controlled myogenic differentiation and morphological changes, depending on their groove size, in C2C12 myoblasts

Additional file 1 of Serum- and xeno-free culture of human umbilical cord perivascular cells for pediatric heart valve tissue engineering

Additional file 1. Supplemental Materials and Methods