Bioactive composites based on double network approach with tailored mechanical, physico‐chemical, and biological features

Abstract

Hyaluronic acid (HA)-based hydrogels are one of the most promising naturally derived biomaterials for tissue engineering applications, as they can play an important role in many key cellular processes. In this study, HA was chemically functionalized with photo-cross-linkable motifs by reacting with methacrylic anhydride (MA) to obtain methacrylated hyaluronic acid (MeHA). A range of MA/HA molar ratios was used to obtain different degrees of substitution (DS) ranging from 3.5% to 74.5%, as showed by nuclear magnetic resonance and attenuated total reflection spectroscopy. By fine tuning the DS, the chemical reaction parameters, and the polymer concentration, it was demonstrated the possibility to tailor their mechanical features. Double network (DN) hydrogels were prepared through the synergic use of MeHA and polyethylene glycole diacrylate (PEGDA). To improve the biological properties of DN hydrogels, bioactive solid signals such as hydroxyapatite nanoparticles (HAp) prepared by sol-gel approach were used in combination with DN hydrogels to obtain an advanced composite material with dual function in terms of mechanical and biological support for soft/hard tissue formation. The results highlighted that composite-DN hydrogels showed a 10-time increase of the storage modulus, if compared to neat MeHA, and an early alkaline phosphatase expression from human mesenchymal stem cells in basal medium. This work can be considered a first systematic approach for the designing of photo-cross-linkable hydrogels, based on a combination of natural/synthetic polymers and HAp, that could be applied in three-dimensional additive manufacturing techniques such as stereolithography. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3079-3089, 2018.

In vitro and in vivo biocompatibility and inflammation response of methacrylated and maleated hyaluronic acid for wound healing

“…Modied HA synthesis and network preparation MEHA and MAHA materials were synthesized following a protocol previously described. 8,37,47 Briey, hyaluronic acid sodium salt (HAs, M w ¼ $340 kDa, Bloomage Freda Biopharm Co. Ltd., Shandong, China) was functionalized with methacrylic (ME; Sigma Aldrich) and maleic anhydride (MA, Kelong Chemical Co. Ltd.) to bind photoactive polymerizable moieties on the polymer chain ( Fig. 1a).…”

“…32,33 To overcome these issues, chemical crosslinking of HA, by chemical modications, has been widely studied. 8,[34][35][36][37] In particular, such chemical modications allow to increase degradation time and improve stability in physiological environment. 3 A wide spectrum of chemically different HA-based products has been reported in literature with different physico-chemical properties.…”

“…Among them, functionalization of the primary and secondary hydroxyl groups using alkyl succinic anhydrides or methacrylic anhydride is the common used technique to obtain photocrosslinkable HA. 8,37,38,46 In previous works, esterication by methacrylic and maleic anhydride, at different degrees of substitution (DS), has been used to synthesize methacrylated (MEHA) and maleated (MAHA) HA materials, respectively. 8,37,47 In particular, it has been highlighted the possibility to ne control the DS of HA matrix to obtain photocrosslinkable hydrogels with modulated adsorption capability and mechanical properties.…”

“…8,37,38,46 In previous works, esterication by methacrylic and maleic anhydride, at different degrees of substitution (DS), has been used to synthesize methacrylated (MEHA) and maleated (MAHA) HA materials, respectively. 8,37,47 In particular, it has been highlighted the possibility to ne control the DS of HA matrix to obtain photocrosslinkable hydrogels with modulated adsorption capability and mechanical properties. 47 Here, the biocompatibility of MEHA and MAHA hydrogels was explored by in vitro and in vivo studies to estimate their effect on cell proliferation and tissue inammation.…”

Biodegradable, anti‐adhesive and tough polyurethane hydrogels crosslinked by triol crosslinkers

“…However, most of the hydrogels are nonbiodegradable or mechanical weakness, which limit their applications. Therefore, improved strategies are often needed (Annabi et al, ; D'Amora et al, ; Tian et al, ; Wang, Zhang, Tsang, Wan, & Wu, ). Proper degradation rate and mechanical properties are essential properties of hydrogels for intended applications.…”