Synthesis and Characterization of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering

Abstract

Novel, injectable hydrogels were developed that solidify through a dual-gelation, physical and chemical, mechanism upon preparation and elevation of temperature to 37°C. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant epoxy rings and a hydrolytically-degradable polyamidoamine-based diamine crosslinker were synthesized, characterized, and combined to produce in situ forming hydrogel constructs. Network formation through the epoxy-amine reaction was shown to be rapid and facile, and the progressive incorporation of the hydrophilic polyamidoamine crosslinker into the hydrogel was shown to mitigate the often problematic tendency of thermogelling materials to undergo significant post-formation gel syneresis. The results suggest that this novel class of injectable hydrogels may be attractive substrates for tissue engineering applications due to the synthetic versatility of the component materials and beneficial hydrogel gelation kinetics and stability.

Development of injectable, stimuli-responsive biomaterials as active scaffolds for applications in advanced drug delivery and osteochondral tissue regeneration

“…97 In our research lab, we are able to synthesize magneto-responsive nanocomposite hydrogels by incorporating aminefunctionalized iron (III) oxide nanoparticles into pNiPAAm-based thermogelling macromers with pendant epoxide rings developed by . 63 The key advantage of this technique is that the covalent bonds between the nanoparticles and the scaffold prevent the nanoparticles from leaching out. However, this method is generally less cost-effective than the other methods presented.…”

“…58 Due to PNiPAAm's thermal transition properties, PNiPAAm-based hydrogels have been successfully used as injectable scaffolds because they are able to deliver viable cell populations and can undergo a thermal gelation without having toxic chemical crosslinkers in the injectable hydrogel formulation. 62 However, the challenges that hinder the application of NiPAAm hydrogels from being used as injectable scaffolds are that 63 In their research, they copolymerized PNiPAAm with glycidyl methacrylate (GMA) to form TGMs with pendant epoxy groups which reacted with the amine groups located on the PAMAM, thus forming degradable crosslinks in the hydrogel network. They found that by utilizing PAMAMs as degradable crosslinks they could tune hydrogel swelling/syneresis, degradation time scale and degree of crosslinking ( Fig.…”

“…63 In this work, PNiPAAM was copolymerized with glycidyl methacrylate (GMA) to form a thermogelling macromer with pendant epoxy rings that could interact with the amine groups located on the ends of the PAMAM macromer to form a chemically crosslinked gel network. Thus, the hypothesis of our preliminary experiments was to determine if we could use these same pendant epoxy rings as active sites where functionalized magnetic nanoparticles could chemically bind to the polymer structure, and thereby, endow the nanocomposite hydrogel with unique magnetic properties that permit spatiotemporally-controlled signaling using an external magnetic field (Fig.…”

“…The thermogelling macromer p(NiPAAmco-GMA) was synthesized by free radical polymerization as previously reported. 63 30 g of the comonomers, NiPAAm and GMA at 92.5 and 7.5 mol %, respectively, were dissolved in 300 mL of either DMF or 1,4 Dioxane and polymerized at 65 ºC under a nitrogen atmosphere. AIBN was added as a free radical initiator at 0.7 mol % of the total monomer content, and the reaction mixture was continuously stirred for 16 h. 0.3 g of 4-methoxyphenol inhibitor was added to the reaction mixture to ensure that the chemical reaction had ended.…”

“…63 were mixed for ~ 30 s at 4 °C in a vial to make 1 mL of the injectable hydrogel solution (Fig. 20).…”