Evaluation of Composition Effects on the Physicochemical and Biological Properties of Polypeptide-Based Hydrogels for Potential Application in Wound Healing

Abstract

In this study, the effect of crosslinking and concentration on the properties of a new library of low-concentration poly(Lys60-ran-Ala40)-based hydrogels for potential application in wound healing was investigated in order to correlate the hydrogel composition with the desired physicochemical and biofunctional properties to expand the assortment of poly-l-lysine (PLL)-based hydrogels suitable for wound healing. Controlled ring-opening polymerization (ROP) and precise hydrogel compositions were used to customize the physicochemical and biofunctional properties of a library of new hydrogels comprising poly(l-lysine-ran-l-alanine) and four-arm poly(ethylene glycol) (P(KA)/4-PEG). The chemical composition and degree of crosslinking via free amine quantification were analyzed for the P(KA)/4-PEG hydrogels. In addition, the rheological properties, pore morphology, swelling behavior and degradation time were characterized. Subsequently, in vitro cell studies for evaluation of the cytotoxicity and cell adhesion were performed. The 4 wt% 1:1 functional molar ratio hydrogel with P(KA) concentrations as low as 0.65 wt% demonstrated low cytotoxicity and desirable cell adhesion towards fibroblasts and thus displayed a desirable combination of properties for wound healing application.

HATMSC Secreted Factors in the Hydrogel as a Potential Treatment for Chronic Wounds—In Vitro Study

“…The cross-linker used did not exhibit any toxicity to fibroblasts, endothelial cells or to keratinocytes when compared to standard 2D tissue culture controls. Consistent with our study, collagen cross-linking with 4-arm PEG succinimidyl glutarate did not affect dermal fibroblast viability [26,27]. Our results suggested that the composed hydrogel is biocompatible with living cells and suitable for further in vivo examination.…”

Investigation of the 3D Printability of Covalently Cross-Linked Polypeptide-Based Hydrogels

“…As discussed in a study by Giliomee et al , the equilibrium swelling ratio (ESR) is closely related to the network structure of hydrogels. The ESR of the composite microgel scaffolds followed the same trend as the pore sizes.…”

“…"Partially Cross-Linked" Inks. The cross-linking between P(KA) and 4-PEG-SG was well-studied in Giliomee et al, 25 and the phase plot was employed to identify soft pliable gels. For the partially cross-linked inks, the soft gel with a concentration of 2 wt % and a 4:1 molar ratio was selected for further investigation.…”

“…Poly­(Lys 60 - ran -Ala 40 ) P­(KA) (synthesized as described in Giliomee et al) (200 mg) was dissolved in 15 mL of distilled water. 4-Azidobenzoic acid solution (2 M, 1.0 mL, 0.24 mmol), EDC (70 mg, 0.45 mmol), and TEMED (150 μL) were added to the P­(KA) solution.…”

“…This hydrogel was previously reported as having good biocompatibility and antibacterial properties. 24 In a recent study by Giliomee et al, 25 the compositional effects of P(KA)/4-PEG were further evaluated for potential applications in wound healing. In this investigation, two approaches to developing P(KA)/4-PEG into 3D printable biomaterial inks were investigated.…”