Research Projects

Bone, being a rigid & mineralized tissue, is mainly made up of inorganic hydroxyapatite (HA) nanocrystals with organic components such as bone cells, collagen, and extracellular matrix (ECM). However, intensifying diseases such as osteomyelitis, osteoarthritis, etc., demonstrate a severe impairment to the integrity and regeneration of bone tissue. In this line, tissue engineering methodologies involving the amalgamation of biomaterials with cells and added biological cues are beneficial for lessening the antagonistic effects of the linked complications. Yet, the main challenges in engineering human tissues with highly active cells are the insufficient oxygen supply, variations in mimicking the native ECM, and immune rejection of these implants. Thus, artificial bone scaffolds must be modified to augment their functionality. Previous literature studies have utilized peroxides or fluorinated compounds in polymer matrices for oxygen release in several tissue engineering applications. However, a major challenge has been the burst release of oxygen from the scaffold when immersed in water and the immune rejection of the scaffolds in vivo. Likewise, incorporating native bone ECM aids in supplementing bone cells with positive cellular properties like adhesion, migration, and differentiation. Macrophages are key players in acute inflammation within the immune system, with two primary subsets: M1 macrophages driving the inflammatory response and M2 macrophages contributing to anti-inflammatory tissue repair. Thus, developing skilled next-generation strategies to synergistically enhance oxygen accessibility, ECM mimic, and immune-modulation in tissue-engineered implants, particularly during the initial engraftment stage, might aid in lessening cell death triggered by hypoxia. To address these challenges, I would aim towards fabricating a 3D bio-printed multifunctional scaffold with osteogenic, ECM mimicking, and immune-modulatory effects of hydroxyapatite (HAP) coated sodium percarbonate (SPC) microparticles consisting of encapsulated macrophages. In this context, I will utilize a diffusion barrier made of an HAP layer to slow down oxygen release from SPC microparticles. To enhance immune modulation, M2 macrophages will be encapsulated within MEHA hydrogel. Also, solubilized bone ECM would be incorporated in the MEHA bioink for effective bone-mimicking characteristics. The fabricated scaffold could be easily tuned for in vitro and in vivo experiments to achieve varied oxygen release kinetics, ECM-mimicking properties, and successful immune modulation for regenerative medicine. This scaffold will aid in achieving successful bone ECM mimic, sustained oxygen release, and immunologic characteristics. This innovation holds immense potential not only in orthopedics but also as a blueprint for engineering complex vascularized and immunologically compatible tissues.