Research

Life Sciences & Biotechnology

Title :

Elucidating the individual and combinatorial effects of cell contact guidance, biomechanical stimulation and BMP-12 signaling in tendon tissue engineering

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Sunil Kumar Boda, Indian Institute Of Technology (IIT) Indore, Madhya Pradesh

Timeline Start Year :

2022

Timeline End Year :

2024

Contact info :

Equipments :

Details

Executive Summary :

Tendons, which connect muscles to bones and play a crucial role in load transfer, are prone to tendinopathy, particularly in sports personnel and aged populations. Current surgical treatments, such as autografts and allografts, have limited success due to mechanical mismatch between the graft and injured tissue, leading to scar tissue formation and retears. Tissue engineering is a promising approach to repair torn tendons and restore their mechanical function. Fabricating anisotropic nanofibrillar scaffolds that present physical contact guidance cues to orient resident cells along the fibril matrix is a potent strategy. To design biomimetic scaffolds with similar structure and biomechanics, aligned 2D nanofiber membranes of biodegradable polymers such as PLGA and chitosan will be expanded in 3D to permit cell/tissue infiltration. The expanded nanofiber meshes will be infused with cell-laden gelatin methacrylol hydrogel and UV-crosslinked. The effect of physical contact guidance on tenogenesis will be studied. Mechanical stimulation of cell-laden anisotropic nanofibrillar constructs will be optimized for maximum collagen alignment and strengthening needed for scarless tendon healing. Recombinant human BMP-12/GDF-7 will be delivered to cells using dermatan sulfate carriers, which form 1-5% of tendon dry weight and collagen at 60-85 wt.%. Short peptide mimics of BMP-12/GDF-7 will be designed using Uniprot and identified as homologous fragments. The most potent BMP-12 peptide mimic and rhBMP-12 will be compared for tenogenesis and incorporated into the anisotropic 3D nanofibrillar scaffolds, with tendon-specific marker expression assessed.

Total Budget (INR):

32,01,000

Organizations involved