Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering

Abstract

The development of advanced scaffolds that recapitulate the anisotropic mechanical behavior and biological functions of the extracellular matrix in leaflets would be transformative for heart valve tissue engineering. In this study, anisotropic mechanical properties were established in poly(ethylene glycol) (PEG) hydrogels by crosslinking stripes of 3.4 kDa PEG diacrylate (PEGDA) within 20 kDa PEGDA base hydrogels using a photolithographic patterning method. Varying the stripe width and spacing resulted in a tensile elastic modulus parallel to the stripes that was 4.1 to 6.8 times greater than that in the perpendicular direction, comparable to the degree of anisotropy between the circumferential and radial orientations in native valve leaflets. Biomimetic PEG-peptide hydrogels were prepared by tethering the cell-adhesive peptide RGDS and incorporating the collagenase-degradable peptide PQ (GGGPQG↓IWGQGK) into the polymer network. The specific amounts of RGDS and PEG-PQ within the resulting hydrogels influenced the elongation, de novo extracellular matrix deposition and hydrogel degradation behavior of encapsulated valvular interstitial cells (VICs). In addition, the morphology and activation of VICs grown atop PEG hydrogels could be modulated by controlling the concentration or micro-patterning profile of PEG-RGDS. These results are promising for the fabrication of PEG-based hydrogels using anatomically and biologically inspired scaffold design features for heart valve tissue engineering.

Extrusion-based 3D printing of poly(propylene fumarate) scaffolds with hydroxyapatite gradients

“…10 mm length × 10 mm width × 2.5 mm height (approximate scaffold thickness) scaffolds were compressed perpendicular to their short axis at a cross-head speed of 0.5 mm/min after an initial pre-load of 25 N, following previous work [34]. The compressive modulus (elastic region between a fixed strain of 0.20–0.30 %, Poisson ratio = 0.5) was calculated using a Python script (see Supplemental Information) [36, 37]. …”

3D bioprinting for engineering complex tissues

“…The Khademhosseini group developed PEG:gelatin methacrylate (PEG:GelMA) and carbon nanotube-incorporated photocrosslinkable gelatin methacrylate (CNT:GelMA) composites with tunable mechanical and degradation properties that could have such applications (Shin et al 2013). Similarly, the West group (Zhang et al 2015) developed a low molecular weight-high molecular weight PEG composite which could mimic the anisotropy of heart valve leaflet moduli. These kind of composites further expand the options available to researchers in bioprinting, and may lead to more complex and biomimetic structures.…”

Injectable hyaluronic acid/PEG-p(HPMAm-lac)-based hydrogels dually cross-linked by thermal gelling and Michael addition

“…This high water content make them compatible with most living tissues.Their viscoelastic and rubbery nature permit their administration into a living host with minimal damage to surrounding tissues, and, ultimately, their mechanical properties can be tailored to closely match those of natural tissues [2,3]. Because of their appealing characteristics, hydrogels, alone or combined with cells, have been used to engineer a variety of tissues in vitro and in vivo [4,5] and, loaded with drugs, found application in the controlled drug delivery field [6,7]. Among all types of hydrogels, in situ-gelling injectable hydrogels have been extensively employed as cell and drug carriers for in vitro and in vivo applications [8].…”