Anisotropic Poly(Ethylene Glycol)/Polycaprolactone Hydrogel–Fiber Composites for Heart Valve Tissue Engineering

Abstract

The recapitulation of the material properties and structure of the native aortic valve leaflet, specifically its anisotropy and laminate structure, is a major design goal for scaffolds for heart valve tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are attractive scaffolds for this purpose as they are biocompatible, can be modified for their mechanical and biofunctional properties, and can be laminated. This study investigated augmenting PEG hydrogels with polycaprolactone (PCL) as an analog to the fibrosa to improve strength and introduce anisotropic mechanical behavior. However, due to its hydrophobicity, PCL must be modified prior to embedding within PEG hydrogels. In this study, PCL was electrospun (ePCL) and modified in three different ways, by protein adsorption (pPCL), alkali digestion (hPCL), and acrylation (aPCL). Modified PCL of all types maintained the anisotropic elastic moduli and yield strain of unmodified anisotropic ePCL. Composites of PEG and PCL (PPCs) maintained anisotropic elastic moduli, but aPCL and pPCL had isotropic yield strains. Overall, PPCs of all modifications had elastic moduli of 3.79±0.90 MPa and 0.46±0.21 MPa in the parallel and perpendicular directions, respectively. Valvular interstitial cells seeded atop anisotropic aPCL displayed an actin distribution aligned in the direction of the underlying fibers. The resulting scaffold combines the biocompatibility and tunable fabrication of PEG with the strength and anisotropy of ePCL to form a foundation for future engineered valve scaffolds.

Anisotropic poly (glycerol sebacate)-poly (ϵ-caprolactone) electrospun fibers promote endothelial cell guidance

“…Earlier reports have also highlighted the use of aligned scaffolds for tissue engineering (Yang et al , 2005; Meng et al , 2010; Xie et al , 2010; Nguyen et al , 2012; Tseng et al , 2014). For example, our recent study on PGS-gelatin fibrous scaffold indicates that cardiomyocytes seeded on aligned scaffolds showed higher expression of sarcomeric α-actinin, Cx-43 and cardiac troponin I (Kharaziha et al , 2013).…”

Dextran-based hydrogel formed by thiol-Michael addition reaction for 3D cell encapsulation

“…Various hydrogels have been used for 3D cell encapsulation, including natural-derived hydrogels (e.g., Matrigel TM [19], collagen [20,21], and fibrin [22]), as well as synthetic hydrogels (e.g., polyethylene glycol (PEG) [23][24][25][26][27], polyvinyl alcohol (PVA) [28], and polyhydroxyethyl methacrylate (PHEMA) [29]). Although natural-derived hydrogels have excellent biocompatibility, the disadvantages of high batch-to-batch variations, undefined matrix compositions and restricted modification possibilities [1,30] significantly limit their applications.…”

Fabrication of Aligned Nanofiber Polymer Yarn Networks for Anisotropic Soft Tissue Scaffolds

“…57-60 Recently, fiberreinforced hydrogel composite scaffolds were designed to form 3D structures for heart valve tissue engineering. [61][62][63] The hydrogels could provide suitable 3D microenvironment for the cells' …”