Clickable Granular Hydrogel Scaffolds for Delivery of Neural Progenitor Cells to Sites of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious condition with limited treatment options. Neural progenitor cell (NPC) transplantation is a promising treatment option, and the identification of novel biomaterial scaffolds that support NPC engraftment and therapeutic activity is a top research priority. The objective of this study is to evaluate in situ assembled poly (ethylene glycol) (PEG)-based granular hydrogels for NPC delivery in a murine model of SCI. Microgel precursors are synthesized by using thiol-norbornene click chemistry to react four-armed PEG-amide-norbornene with enzymatically degradable and cell adhesive peptides. Unreacted norbornene groups are utilized for in situ assembly into scaffolds using a PEG-di-tetrazine linker. The granular hydrogel scaffolds exhibit good biocompatibility and do not adversely affect the inflammatory response after SCI. Moreover, when used to deliver NPCs, the granular hydrogel scaffolds supported NPC engraftment, do not adversely affect the immune response to the NPC grafts, and successfully support graft differentiation toward neuronal or astrocytic lineages as well as axonal extension into the host tissue. Collectively, these data establish PEG-based granular hydrogel scaffolds as a suitable biomaterial platform for NPC delivery and justify further testing, particularly in the context of more severe SCI.

Chitosan-Based Microparticle Encapsulated Acinetobacter baumannii Phage Cocktail in Hydrogel Matrix for the Management of Multidrug Resistant Chronic Wound Infection

Objectives: Multi-drug resistant bacteria have been implicated in various debilitating infections that have led to life loss. This study developed an approach to tackle multidrug resistant Acinetobacter baumannii infection in a chronic wound model through A. baumannii phage encapsulation with resuspension in hydrogel. Materials and Methods: Two isolates of A. baumannii-specific lytic phases ɸAB140 and ɸAB150 alone, in combination (cocktail) encapsulated within a chitosan (CS) microparticle was suspended in CS hydrogel and evaluated for their therapeutic efficacy to ensure bacterial clearance in A. baumannii induced diabetic wound infection. Microencapsulation of the phage was carried out using ionic gelation techniques Biological characterization via cell cytoxicity, in vivo wound healing, histology and histomorphometry was carried out. Results: Two characterized A. baumannii phages (ɸAB140 and ɸAB150), specific to twenty A. baumannii isolates, were isolated. The encapsulated CS microparticle hydrogel exhibited a pH of 5.77 ± 0.05. The wound size reduction was most pronounced in formulation C2, which showed statistically significant wound seize reduction on days 4 and 7, 56.79 ± 2.02% and 62.15 ± 5.11%, respectively. The optimized concentration of C2 was not toxic to the cells as it adequately supported cell growth with a proliferation rate of 215 ± 7.89% compared to control (107.32 ± 4.55%). Conclusion: Microparticle carrier technology was used to show the lytic activity against multi drug-resistant A. baumannii. In vivo results showed significant wound size reduction that was most pronounced in formulation C2 on day 4.