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.

Highlights

  • The intricate process of wound healing is well understood [1,2,3,4]

  • We investigated the effect of crosslinking and concentration on the properties of a new library of low-concentration poly(Lys60-ran-Ala40)-based hydrogels

  • By controlling the synthesis of the polypeptide, using a facile method of controlled ring-opening polymerization (ROP), we were able to target the lysine to alanine ratio (K/A), molecular weight and a narrow molecular weight distribution

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Summary

Introduction

The intricate process of wound healing is well understood [1,2,3,4]. This process includes the three overlapping phases of wound healing, namely, inflammation, proliferation and remodeling. The ideal treatment should provide a combination of rapid wound closure, control over infections, prompt pain relief, minimal inconvenience to the patient and minimal scarring while maintaining low treatment costs and risks [8] Advanced treatments, such as bioactive dressings and skin substitutes, aim to achieve these criteria by mimicking the native skin and actively partaking in the wound healing process [7,9,10,11,12]. By controlling the synthesis of the polypeptide, using a facile method of controlled ROP, we were able to target the lysine to alanine ratio (K/A), molecular weight and a narrow molecular weight distribution This allowed carefully controlling the degree of crosslinking using stoichiometric ratios of the functional groups of the polypeptide and the multi-arm PEG while maintaining low total polymer concentrations

Materials
Random NCA Copolymerization
Deprotection of Polypeptides
Preparation of Polypeptide-Based Hydrogels
Amine Quantification
Pore Morphology
Swelling Behavior
Preparation of Controlled Polypeptides
Preparation of a Library of Hydrogels
The Effect of Crosslinking and Concentration on the Hydrogel Netwwoorkk
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