Syndecan-4 functionalization of tissue regeneration scaffolds improves interaction with endothelial progenitor cells.

Key to most implanted cell free scaffolds for tissue regeneration is the ability to sequester and retain undifferentiated mesenchymal stem cells at the repair site. In this report, syndecan-4, a heparan sulfate containing proteoglycan, was investigated as a unique molecule for use in scaffold functionalization. An electrospun hybrid scaffold comprised of poly (glycerol) sebacate (PGS), silk fibroin and type I collagen (PFC) was used as a model scaffold to develop a procedure and test the hypothesis that functionalization would result in increased scaffold binding of endothelial progenitor cells (EPCs). For these studies both Syndecan-4 and stromal derived factor-1α (SDF-1α) were used in functionalization PFC. Syndecan-4 functionalized PFC bound 4.8 fold more SDF-1α compared to nonfunctionalized PFC. Binding was specific as determined by heparin displacement studies. After culture for 7 days, significantly, more EPCs were detected on PFC scaffolds having both syndecan-4 and SDF-1α compared to scaffolds of PFC with only syndecan-4, or PFC adsorbed with SDF-1α, or PFC alone. Taken together, this study demonstrates that EPCs can be bound to and significantly expanded on PFC material through syndecan-4 mediated growth factor binding. Syndecan-4 with a multiplicity of binding sites has the potential to functionalize and expand stem cells on a variety of scaffold materials for use in tissue regeneration.

Fabrication of biodegradable foams for deep tissue negative pressure treatments.

Devices for negative pressure wound therapy (NPWT) rely on compressible foams operating at the tissue-device interface. Clinically used foams are nonabsorbable and if used on deep wounds or left in place for an extended period of time, excessive cell ingrowth and formation of granulation tissue into the foam may require a surgical procedure to remove the foam. Foams with fast degradation and with low immunogenicity and fibrotic response are required. Foams composed of combinations of poly(lactide-co-glycolide) (PLGA), poly(lactide-co-caprolactone) (PLCL), and polycaprolactone (PCL) were created by combined salt leaching and solvent displacement protocols. In vitro and in vivo degradation studies and mechanical properties of foams were evaluated and compared to clinically used poly(vinyl alcohol) (PVA) foam and PCL foams. Foams composed of PLGA (50:50 lactide:glycolide) of low molecular weight blended with PCL maintained mechanical properties and degraded significantly after 21 days of subcutaneous implantation in rats. The most ideal formulations for use in NPWT were identified as copolymeric PLGA (Mn 3000 Da) at a lactide:glycolide ratio of 50:50 combined with PCL at either a 75:25 or 50:50 ratio, and copolymeric PLGA (Mn 7500 Da) at a lactide:glycolide ratio of 50:50 combined with PCL at a 50:50 ratio. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1998-2007, 2018.

Mitigation of diabetes-related complications in implanted collagen and elastin scaffolds using matrix-binding polyphenol.

There is a major need for scaffold-based tissue engineered vascular grafts and heart valves with long-term patency and durability to be used in diabetic cardiovascular patients. We hypothesized that diabetes, by virtue of glycoxidation reactions, can directly crosslink implanted scaffolds, drastically altering their properties. In order to investigate the fate of tissue engineered scaffolds in diabetic conditions, we prepared valvular collagen scaffolds and arterial elastin scaffolds by decellularization and implanted them subdermally in diabetic rats. Both types of scaffolds exhibited significant levels of advanced glycation end products (AGEs), chemical crosslinking and stiffening -alterations which are not favorable for cardiovascular tissue engineering. Pre-implantation treatment of collagen and elastin scaffolds with penta-galloyl glucose (PGG), an antioxidant and matrix-binding polyphenol, chemically stabilized the scaffolds, reduced their enzymatic degradation, and protected them from diabetes-related complications by reduction of scaffold-bound AGE levels. PGG-treated scaffolds resisted diabetes-induced crosslinking and stiffening, were protected from calcification, and exhibited controlled remodeling in vivo, thereby supporting future use of diabetes-resistant scaffolds for cardiovascular tissue engineering in patients with diabetes.