Physico-Chemical Characterization and In Vitro Biological Evaluation of a Bionic Hydrogel Based on Hyaluronic Acid and l-Lysine for Medical Applications.

Giuseppe Alonci,Sabrina Sommatis,Lidia Nachbaur,Nicola Zerbinati,Agata Janowska,Roberto Mocchi,Elsa Liga,Maria Chiara Capillo

doi:10.3390/pharmaceutics13081194

Giuseppe Alonci, Sabrina Sommatis + Show 6 more

Open Access

https://doi.org/10.3390/pharmaceutics13081194

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Abstract

Hyaluronic acid (HA) is an endogenous polysaccharide, whose hydrogels have been used in medical applications for decades. Here, we present a technology platform for stabilizing HA with a biocrosslinker, the amino acid l-Lysine, to manufacture bionic hydrogels for regenerative medicine. We synthetized bionic hydrogels with tailored composition with respect to HA concentration and degree of stabilization depending on the envisaged medical use. The structure of the hydrogels was assessed by microscopy and rheology, and the resorption behavior through enzymatic degradation with hyaluronidase. The biological compatibility was evaluated in vitro with human dermal fibroblast cell lines. HA bionic hydrogels stabilized with lysine show a 3D network structure, with a rheological profile that mimics biological matrixes, as a harmless biodegradable substrate for cell proliferation and regeneration and a promising candidate for wound healing and other medical applications.

Highlights

We present a new, straightforward platform technology for the crosslinking of hyaluronic acid with L-Lysine by using ethylcarbodiimide hydrochloride (EDC)/NHS, non-toxic coupling agents, that allow the preparation of homogeneous bionic hydrogels with a three-dimensional network, with tunable composition, Hyaluronic acid (HA) concentration, degree of modification and rheological profile, tailored for specific uses in regenerative medicine
Hyaluronic acid sodium salt (1 MDa, cosmetic grade) was supplied by HTL (Paris, France), N-hydroxysuccinimmide 98% was supplied by Alfa Aesar (Haverhill, MA, USA), while L-Lysine 98% and N-(3-Dimethylaminopropyl)-N0 -ethylcarbodiimide hydrochloride (EDC) 98% were purchased from Sigma-Aldrich
The synthetic strategy that we report is a simple, one pot synthesis and requires only one purification step, dialysis against Phosphate-buffered saline (PBS) at physiological pH, and we show that the hydrogel is stable even after autoclaving

Summary

Introduction

Hyaluronic acid (HA) is a structural building block widely present in the human body throughout the extracellular matrix, and vitreous, connective, epithelial and neural tissues [1,2]. Despite its structural simplicity and repetitiveness, a glycosaminoglycan consisting of N-acetylglucosamine–glucuronic acid, disaccharide units repeating in a linear fashion, HA plays a role in a broad spectrum of physiological processes, such as in morphogenesis and tissue organization, cell proliferation, differentiation and migration, among others [3,4,5]. The biochemistry of HA is a field of intensive research due to the wide-ranging roles of this multitasking molecule in living systems and for developing further medical applications [3,9]

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