Bioinspired Engineering of Poly(ethylene glycol) Hydrogels and Natural Protein Fibers for Layered Heart Valve Constructs

Abstract

Layered constructs from poly(ethylene glycol) (PEG) hydrogels and chicken eggshell membranes (ESMs) are fabricated, which can be further cross-linked by glutaraldehyde (GA) to form GA-PEG-ESM composites. Our results indicate that ESMs composed of protein fibrous networks show elastic moduli ∼3.3-5.0 MPa and elongation percentages ∼47-56%, close to human heart valve leaflets. Finite element simulations reveal obvious stress concentration on a partial number of fibers in the GA-cross-linked ESM (GA-ESM) samples, which can be alleviated by efficient stress distribution among multiple layers of ESMs embedded in PEG hydrogels. Moreover, the polymeric networks of PEG hydrogels can prevent mineral deposition and enzyme degradation of protein fibers from incorporated ESMs. The fibrous structures of ESMs retain in the GA-PEG-ESM samples after subcutaneous implantation for 4 weeks, while those from ESM and GA-ESM samples show early degradation to certain extent, suggesting the prevention of enzymatic degradation of protein fibers by the polymeric network of PEG hydrogels in vivo. Thus, these GA-PEG-ESM layered constructs show heterogenic structures and mechanical properties comparable to heart valve leaflets, as well as improved functions to prevent progressive calcification and enzymatic degeneration, which are likely used for artificial heart valves.

Biologically Inspired Scaffolds for Heart Valve Tissue Engineering via Melt Electrowriting

“…More recently, biomimetic designs and fabrication strategies have gained increasing attention in the attempt to recapitulate the biomechanical properties of the native tissue. [30][31][32][33][34][35] In particular, fibrous scaffolds that recapitulate several aspects of the extracellular matrix such as fiber diameter and pore size ranges are considered promising, but they might suffer poor cellular infiltration and lack of control over microarchitecture. [36] Directional electrospinning [20,21] and new advanced fiber-forming techniques such as jet-spraying, [17] jet-spinning, [37] and double component electrodeposition [38] have been developed to overcome these limitations.…”

Bio-inspired anisotropic polymeric heart valves exhibiting valve-like mechanical and hemodynamic behavior

“…However, SF mats alone showed low resistance to platelet adhesion and enzyme degradation in vivo [18,41]. PEGDA hydrogels that had shown good biocompatibility and low-fouling properties [16] were then used to prepare PEGDA-SF composites. The interpenetrating structures of PEGDA-ISF and PEGDA-ASF composites (Fig.…”

“…In this study, isotropic and anisotropic silk fibroin (SF) membranes were produced by electrospinning methods. SF membranes were further used to fabricate PHVs to-gether with poly(ethylene glycol) diacrylate (PEGDA) hydrogels, which exhibited excellent biocompatibility and low-fouling property [16]. The microstructures, mechanical properties and hemodynamic performance of these PHVs were studied.…”

Nanofiber‐Based Hydrogels: Controllable Synthesis and Multifunctional Applications

“…On the other hand, owing to the high specific surface area of nanofibers, the porous nanofiber networks within the NFHGs can provide more adhesion sites and physical guidance for cells, thereby greatly promoting the stem cell adhesion, proliferation, differentiation, and migration . To date, various NFHGs with differentiated structures and components have been designed and prepared for the application of tissue engineering, mainly involving bone tissue engineering, tendon tissue engineering, cartilage tissue engineering, nerve regeneration, skin flap regeneration, flexor tendon regeneration wound dressings, heart valve engineering, ventral hernia repair, and so on …”

“…[30,33,65] To date, various NFHGs with differentiated structures and components have been designed and prepared for the application of tissue engineering, mainly involving bone tissue engineering, tendon tissue engineering, cartilage tissue engineering, nerve regeneration, skin flap regeneration, flexor tendon regeneration wound dressings, heart valve engineering, ventral hernia repair, and so on. [66][67][68][69][70][71]…”