In collaboration with Drs. Keselowsky and Bose at UF, we are evaluating the potential of localized delivery of the immunomodulatory enzyme, Indoleamine 2,3-dioxygenase, using an injectable formulation derived from decellularized rat peripheral nerves. This approach aims to decrease neuroinflammation and promote locomotor recovery in injured rat spinal cords. 

During my postdoctoral work, I developed an injectable hydrogel formulation using decellularized and delipidated porcine/human peripheral nerves. This formulation supports Schwann cell viability and serves as a cell delivery vehicle for spinal cord injections. Currently, we are exploring the potential of these injectable formulations in a contused rat spinal cord model.

Revelant Publications:

1. Agarwal G, Shumard S, McCrary MW, Osborne O, Santiago JM, Ausec B, Schmidt CE. Decellularized porcine peripheral nerve based injectable hydrogels as a Schwann cell carrier for injured spinal cord regeneration. J Neural Eng. 2024;21(4). doi: 10.1088/1741-2552/ad5939. PMID: 38885674. 

2. Agarwal G, Moes K, Schmidt CE. Decellularized human peripheral nerve based injectable formulation for neural tissue regeneration (Manuscript under communication). 

This project was done at NIPER-Ahmedabad, India (PI: Dr. Akshay Srivastava).  The goal of the project was to develop an interconnected porous and electroconductive hydrogel that can accelerate the injured spinal cord regeneration. 

Revelant Publications:

1.  Agarwal G, Kumar N, Srivastava A. Highly elastic, electroconductive, immunomodulatory graphene crosslinked collagen cryogel for spinal cord regeneration. Mater Sci Eng C Mater Biol Appl. 2021;118:111518. doi: 10.1016/j.msec.2020.111518. PMID: 33255073. 

2.  Agarwal G, Roy A, Kumar H, Srivastava A. Graphene-collagen cryogel controls neuroinflammation and fosters accelerated axonal regeneration in spinal cord injury. Biomater Adv. 2022 ;139:212971. doi: 10.1016/j.bioadv.2022.212971. PMID: 35882128.  

The influence of graphene as a nano-crosslinker on the overall porosity and inter-connections between the pores in collagen cryogels was determined using X-ray micro-tomography. We have evaluated the effect of different concentration of amino-functionalized graphene nano-crosslinker on collagen cryogels porosity, pore volume, interconnectivity density, fractal dimensions and pore wall thickness. This study, reveals that the use of graphene as a nano-crosslinker have improved micro-architecture as compare to collagen cryogels in the absence of graphene for tissue engineering applications. 

Revelant Publication

1. Agarwal G, Agrawal AK, Fatima A, Srivastava A. X-ray tomography analysis reveals the influence of graphene on porous morphology of collagen cryogels. Micron. 2021 ;150:103127. doi: 10.1016/j.micron.2021.103127. PMID: 34419716. 

Particle loaded hydrogels have shown to provide prolonged delivery of drug in a controlled manner. We propose that embedding drug-loaded hyaluronic acid (HA) microneedles in supermacroporous collagen type-I (Col-I) cryogel plugs may enhance the hydration and provide prolonged release of drug for ocular diseases. In this study, we have fabricated Col-I cryogel and HA-microneedles embedded Col-I cryogel at sub-zero temperature using 4S-arm Star-PEG as a crosslinker. The fabricated novel Col-I cryogels have shown supermacroporous morphology with solvent uptake capacity of nearly 90% due to large pore volume and high interconnectivity. These features of the cryogel enable the release the drug in a controlled and sustained manner. The fabricated cryogels have demonstrated nearly 50% degradation in simulated tear fluid within 15 days of duration. Moreover, the microneedles incorporated cryogels have shown prolonged release of required therapeutic concentration of drug that may satisfy the present dire need for antibacterial drug delivery in eyes. The variation in the drug release kinetics from Col-I cryogel and HA-microneedles-laden-Col-I cryogels have been studied in different release media (PBS and Simulated tear fluid). 

Revelant Publication

1. KrishnaPriya S*., Agarwal*G, Srivastava A. Hyaluronic microneedle loaded collagen cryogels for ocular drug delivery. J Applied Poly. Sci. 2020; 137: 49285. (*Equal Author)