Syndecan‐4 functionalized elastomeric biomaterial promotes in situ endovascular tissue repair and regeneration

Abstract

While many acellular endovascular biomaterials have been developed to attract endothelial precursors cells (EPCs) to promote tissue repair and regeneration, none of them truly create a conducive microenvironment for EPC adhesion, growth, and differentiation. Syndecan‐4 is a heparan sulfate containing proteoglycan with high affinity and binding specificity for various growth factors, cytokines, chemokines, is a significant component of the endothelial cell glycocalyx. In this study, an endovascular biomaterial composite of type I collagen, poly (glycerol sebacate) and silk fibroin, termed PFC, was functionalized with syndecan‐4 and stromal cell‐derived factor 1 alpha (SDF‐1α) to study the interaction with EPCs. The functionalized biomaterial (PFC_SYN4) significantly promoted the adhesion of EPCs. PFC_SYN4 captured 50% more cells than PFC under dynamic binding conditions (P<0.001) and 20% more cells than PFC under physiological flow conditions (P<0.05). Competitive binding studies showed EPCs bound to PFC_SYN4 in the presence of excess leucocytes. After 2 hours of incubation, average cell spreading area of EPCs on PFC_SYN4 (1252 ± 415 µm2) was significantly greater (P<0.05) than on PFC (1149 ± 392 µm2). At day 4, vWF expression was doubled for cells on PFC and PFC_SYN4. CD31 was upregulated about 3.4 fold in cells cultured on PFC and 7.2 fold in cells cultured on PFC_SYN4 (P<0.05), at day 7, CD31 and vWF expression was significantly greater than on day 4. PFC_SYN4 increased 10.6 fold for vWF and PFC increased 4 fold. PFC_SYN4 had doubled amount of CD31 expression compared to PFC (P<0.05). This study expands our knowledge of the potential benefit of using syndecan‐4 to functionalize acellular biomaterials and facilitate the adhesion, growth, and differentiation of precursor cells in order to further promote tissue repair and regeneration.