Research Projects

Rationale of the study: Peripheral nerve injury (PNI) and spinal cord injury (SCI) result in severe motor and sensory impairments due to poor axonal regeneration and the presence of a chronic, inflammatory microenvironment. Existing treatments such as passive nerve conduits and rigid electrical stimulation (ES) systems lack adaptability to the biochemical dynamics at the injury site, resulting in limited efficacy. This project proposes a next-generation, multifunctional soft nerve wrap system that integrates piezoelectric electrostimulation, real-time biosensing, and a bioactive hydrogel embedded with 4-aminopyridine (4-AP) and MnO₂ nanoparticles. The system delivers (1) localized ES to enhance axonal regrowth, (2) continuous sensing of neurochemical markers like glutamate and reactive oxygen species (ROS), and (3) targeted therapeutic delivery for inflammation control and neuroprotection. Addressing critical barriers: Traditional ES systems operate using static parameters and rigid materials that fail to match the compliance of neural tissue. Similarly, hydrogel-based therapies lack electrical responsiveness or sensing capabilities. Our nerve wrap addresses these gaps by combining soft piezoelectric actuators, dual-mode electrochemical microelectrodes, and an optimized hydrogel layer designed for wrapping and sustained therapeutic release. 4-AP, an FDA-approved potassium channel blocker, promotes conduction and nerve signal propagation, while MnO₂ nanoparticles serve as non-enzymatic antioxidants, reducing oxidative stress and inflammation two key obstacles to effective regeneration. Together, these components create a closed-loop, feedback-driven system for intelligent neuromodulation. Hypothesis: In vivo application of the multifunctional nerve wrap capable of adaptive piezoelectric ES, biochemical sensing, and controlled hydrogel release of 4-AP and MnO₂ will improve axonal regeneration, suppress neuroinflammation, and enhance functional recovery in rodent models of PNI and SCI. Scientific objectives: 1. Hydrogel formulation and optimization: Synthesize and optimize three hydrogel variants embedded with 4-AP and MnO₂, ensuring biocompatibility, degradation rate, and mechanical conformity to the nerve wrap. 2. Device fabrication and in vitro validation: Engineer the nerve wrap using soft elastomers and piezoelectric composites with embedded dual-mode microelectrodes. 3. In vitro testing for biocompatibility: Examine biocompatibility, anti-inflammatory effects, drug release, and electrical functionality using neural cell cultures. 4. In vivo validation in rodents: Apply the device in rat PNI and SCI models to assess axonal regeneration, inflammation levels, and motor function recovery. Main experiments: Hydrogels will be evaluated for therapeutic agent release and tissue compatibility. Real-time biochemical sensing will guide ES parameters based on detected neurochemical levels. Biphasic ES will be delivered through the piezoelectric wrap, modulated by feedback from glutamate and ROS sensors. The hydrogel will deliver sustained doses of 4-AP to restore signal conduction and MnO₂ to reduce inflammation. Histological analyses: • Axonal regeneration (GAP-43) • Myelination (MBP) • Inflammation (Iba1) Significance: This is the first system to integrate a hydrogel-compatible nerve wrap with adaptive piezoelectric stimulation, real-time neurochemical feedback, and sustained anti-inflammatory drug delivery. It represents a major advancement in personalized, minimally invasive neuroregenerative therapy. National and global relevance: Aligned with India’s “Make in India” and healthcare innovation goals, this project supports development of scalable, indigenous technologies. Internationally, it introduces a cost-effective, adaptable platform for treating nerve injuries, with broad potential across neuromodulation and regenerative medicine.