density of 0.58 and jamming can occur. In our laboratory, we crosslink HMPs to each other to generate a stable scaffold, rather than rely on jamming such that the void spaces surrounding the beads are sufficiently large for cellular growth and the scaffold is structurally stable. We termed these bulk hydrogels microporous annealed particle (MAP) scaffolds due to the micron sized voids (pores) formed in between packed beads. MAP scaffolds support modifications with bioactive ligands to modulate cell behavior, can be used for cell culture in vitro, [1][2][3][4][5][6][7][8] and support tissue ingrowth in vivo. [2][3][4][5] Of particular interest is that injection of MAP scaffolds into wound sites results in reduced inflammation and improved tissue regeneration. [3,4,9,10] We have shown that the innate microporosity of MAP scaffolds enables a greater prorepair response in the wound site after stroke compared to a nonporous gel of the same composition. [5] The "plug and play" modularity of MAP building blocks enables the incorporation of different materials, signals, and crosslinking schemes to tune the scaffolds for unique tissue engineering applications. Herein, we demonstrate the generation of hyaluronic acid HMPs, the modification of HMPs with ligands, and the crosslinking of HMPs to form MAP scaffolds using thiol-norbornene and tetrazine-norbornene click reactions and their use in vitro and in vivo.HMP interlinking to form MAP scaffolds can be achieved upon injection due to the shear thinning properties of these granular materials and the use of biocompatible mechanisms for annealing. Our current method to fabricate MAP scaffolds for use in vivo utilizes the coagulation enzyme FXIIIa, which is a transglutaminase. [2,5,11] The HMPs are packed and linked between K and Q peptides, recognized by FXIIIa, on their surface. For applications in wound healing, polyethylene glycol (PEG) HMPs annealed with FXIIIa in situ have been shown to promote cutaneous tissue regeneration by supporting cell migration and support tissue structure formation. In vivo responses to these injectable PEG MAP scaffolds include re-epithelialization, vascular development, and growth of hair follicles. [2] Utilizing the native extracellular matrix component hyaluronic acid (HA) with FXIIIa for scaffold fabrication accelerates brain repair processes after stroke. [5] Compared to both sham injections and nonporous gels, HA MAP reduces Macroporous scaffolds are being increasingly used in regenerative medicine and tissue repair. While the recently developed microporous annealed particle (MAP) scaffolds have overcome issues with injectability and in situ hydrogel formation, limitations with respect to tunability to be able to manipulate hydrogel strength and rigidity for broad applications still exist. To address these key issues, here hydrogel microparticles (HMPs) of hyaluronic acid (HA) are synthesized using the thiol-norbornene click reaction and then HMPs are subsequently annealed into a porous scaffold using the tetrazine-norbornene click reacti...

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The goal of this research was to develop a novel oxygen therapeutic made from a pectin-based hydrogel microcapsule carrier mimicking red blood cells. The study focused on three main criteria for developing the oxygen therapeutic to mimic red blood cells: size (5–10 μm), morphology (biconcave shape), and functionality (encapsulation of oxygen carriers; e.g., hemoglobin (Hb)). The hydrogel carriers were generated via the electrospraying of the pectin-based solution into an oligochitosan crosslinking solution using an electrospinning setup. The pectin-based solution was investigated first to develop the simplest possible formulation for electrospray. Then, Design-Expert® software was used to optimize the production process of the hydrogel microcapsules. The optimal parameters were obtained through the analysis of a total of 17 trials and the microcapsule with the desired morphology and size was successfully prepared under the optimized condition. Fourier transform infrared spectroscopy (FTIR) was used to analyze the chemistry of the microcapsules. Moreover, the encapsulation of Hb into the microcapsule did not adversely affect the microcapsule preparation process, and the encapsulation efficiency was high (99.99%). The produced hydrogel microcapsule system shows great promise for creating a novel oxygen therapeutic.

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standard of care. Because GBM is a brain tumor, tumor resection is conducted using "maximally safe" surgical margins with the goal of removing all cancerous cells while leaving as much of the healthy parenchyma intact as possible. [5] This strategy is particularly important for GBM because damaging or removing the highly specialized healthy brain tissue will result in language, motor, or