Injectable Acylhydrazone‐Linked RAFT Polymer Hydrogels for Sustained Protein Release and Cell Encapsulation

Abstract

A new class of temperature responsive polymer, termed PADO, is synthesized by reversible addition-fragmentation chain-transfer polymerization. Synthesized from copolymerization of diacetone acrylamide (DAAM), di(ethylene glycol) ethyl ether acrylate, and oligo(ethylene glycol) methyl ether acrylate, PADO polymer phase separates at temperature above its lower critical solution temperature (36-42 °C) due to enhanced hydrophobic interactions between the short ethylene glycol side chains. Solution of PADO polymers exhibit injectable shear-thinning properties and reach sol-gel transition rapidly (<5 min) at 37 °C. When the ketone moieties on DAAM are linked by adipic acid dihydrazdie, PADO polymers form crosslinked and injectable acylhydrazone hydrogels, which are hydrolytically degradable at a mild acidic environment owing to the pH sensitive acylhydrazone bonds. The pH-responsive degradation kinetics can be controlled by tuning polymer contents and ketone/hydrazide ratio. Importantly, the injectable PADO hydrogels are highly cytocompatible and can be easily formulated for pH-responsive sustained protein delivery.

Hydrolytically Degradable PEG-Based Inverse Electron Demand Diels–Alder Click Hydrogels

“…Overall, PEGNB CA iEDDA click cross-linked hydrogels produced less of an inflammatory response, as indicated by the CD45 and CD68 staining and subsequent image analysis (Figure c,d). Future studies of the PEGNB CA iEDDA click cross-linked hydrogels can include further functionalization to improve the injectability by adding either a second network that displays shear-thinning compatibilities or a thermosensitive functional group. − Further, since the injectable hydrogel system displayed excellent cytocompatibility with hMSCs and can be further functionalized through norbornene chemistry, applications in injectable cell delivery of hMSCs for musculoskeletal regeneration should be explored.…”

Injectable Hybrid-Crosslinked Hydrogels as Fatigue-Resistant and Shape-Stable Skin Depots

“…The hybrid-crosslinked EPC–DA showed the slowest release, with less than 40% of the lysozymes released over 49 days, as compared to the PEGDA hydrogel, which released 80% over the same duration (Figure C). There have been studies of injectable hydrogels formulated at a high polymer concentration of 20 wt % showing sustained release for over 21 days. , The hybrid-crosslinked EPC–DA shows a substantially longer period of release and at a lower polymer concentration. The slow release from EPC–DA hydrogels could be due to the additional covalent crosslinks that serve to further reduce the mesh size of the hydrogel as corroborated by SEM studies.…”

“…There have been studies of injectable hydrogels formulated at a high polymer concentration of 20 wt % showing sustained release for over 21 days. 80,81 The hybridcrosslinked EPC−DA shows a substantially longer period of release and at a lower polymer concentration. The slow release from EPC−DA hydrogels could be due to the additional covalent crosslinks that serve to further reduce the mesh size the hydrogel as corroborated by SEM studies.…”

Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins

“…Poly (diacetone acrylamide-co-di (ethylene glycol) ethyl ether acrylate-co-oligo (ethylene glycol) methyl ether acrylate), or PADO, was synthesized using reversible addition-fragmentation chain-transfer (RAFT) polymerization as previously reported (Lin et al, 2022). The monomers feed ratios were 29 mol%, 59 mol%, and 13 mol% for diacetone acrylamide, di (ethylene glycol) ethyl ether acrylate, and oligo (ethylene glycol) methyl ether acrylate, respectively.…”

“…Poly (diacetone acrylamide-co-di (ethylene glycol) ethyl ether acrylate-co-oligo (ethylene glycol) methyl ether acrylate), or PADO, was synthesized using reversible additionfragmentation chain-transfer (RAFT) polymerization as previously reported (Lin et al, 2022).…”