Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process.

Lixuan Wang,Yuan Yuan,Jingjing Zhang,Shiyan Dong,Wen Jiang,Yutong Liu,Yifan Ma,Zhaogang Yang

doi:10.3390/polym12051138

Abstract

Injectable hydrogels have been widely applied in the field of regenerative medicine. However, current techniques for injectable hydrogels are facing a challenge when trying to generate a biomimetic, porous architecture that is well-acknowledged to facilitate cell behaviors. In this study, an injectable, interconnected, porous hyaluronic acid (HA) hydrogel based on an in-situ bubble self-generation and entrapment process was developed. Through an amide reaction between HA and cystamine dihydrochloride activated by EDC/NHS, CO2 bubbles were generated and were subsequently entrapped inside the substrate due to a rapid gelation-induced retention effect. HA hydrogels with different molecular weights and concentrations were prepared and the effects of the hydrogel precursor solution’s concentration and viscosity on the properties of hydrogels were investigated. The results showed that HA10-10 (10 wt.%, MW 100,000 Da) and HA20-2.5 (2.5 wt.%, MW 200,000 Da) exhibited desirable gelation and obvious porous structure. Moreover, HA10-10 represented a high elastic modulus (32 kPa). According to the further in vitro and in vivo studies, all the hydrogels prepared in this study show favorable biocompatibility for desirable cell behaviors and mild host response. Overall, such an in-situ hydrogel with a self-forming bubble and entrapment strategy is believed to provide a robust and versatile platform to engineer injectable hydrogels for a variety of applications in tissue engineering, regenerative medicine, and personalized therapeutics.

Highlights

In recent years, injectable biomaterials, which can be applied via minimally invasive methods in the clinic and can be formed into any desired shape to match irregular defects, have gathered much attention in the field of tissue regeneration [1,2,3,4]
Co., Ltd., (Shanghai, China). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC), N-Hydroxysuccinimide (NHS), isoamyl acetate, and sodium pentobarbital were obtained from Aladdin
The chemically cross-linked hyaluronic acid (HA) hydrogel in the presence of EDC and NHS was prepared in a short time, which satisfied the injectability of the hydrogel, and entrapped the CO2 bubbles generated during the process of activating carboxyl group in the viscous hydrogel

Summary

Introduction

Injectable biomaterials, which can be applied via minimally invasive methods in the clinic and can be formed into any desired shape to match irregular defects, have gathered much attention in the field of tissue regeneration [1,2,3,4]. Injectable hydrogels, free-flowing fluids before injection that go through a spontaneous transformation into semisolid hydrogels once a reaction is initiated, have emerged as a promising platform for clinical applications. Polymers 2020, 12, 1138 hydrogel system provides a biocompatible, highly hydrated 3D environment similar to the ECM structure [5,6], but can use minimally invasive procedures to transfer cells more effectively or deliver bioactive molecules to the target site [7,8], filling large, irregular, and complex defects; and reducing recovery time, risk of infection, and patient pain. The presence of the macropores provided the necessary space for the growth of blood vessels and thereby promoted the angiogenesis of the implant

Methods

Results

Conclusion