Overview of Research Programs

The overarching goal of our lab is to engineer functional human tissue that will drive the engine of biomedical innovations for the next century enabling better understanding of diseases, drug discovery and therapeutics. Our research interests are nanocomposite hydrogels, stem cell engineering, stimuli-responsive biomaterials and 3D Bioprinting. The objective of the lab is to generate a cohesive approach for directing stem cell differentiation and fabricating functional artificial tissue interfaces. We hypothesize that the proposed integrated approach will bring together a range of seemingly disparate disciplines that will enable us to address the complexity associated with engineering functional tissue interfaces in a manner that is otherwise not possible. To address the grand engineering challenge, our research focuses on:

Bio-instructive Materials for In Situ Tissue Regeneration

In situ tissue regeneration harnesses the body’s regenerative potential to control and direct cell functions for tissue repair. The design of biomaterials for in situ tissue engineering requires precise control over biophysical and biochemical cues to mobilize endogenous cells to the site of injury. Specifically, the native microenvironment needs to provide the necessary cues to direct host stem/progenitor cells to repopulate implanted, acellular scaffolds. These cues need to induce regeneration by modulating extracellular microenvironment or drive cellular reprogramming for in situ tissue repair. 

In our lab, we design a range of bioresponsive materials to control and direct the body’s regenerative capacity for tissue-specific regeneration. Specifically, biomaterials loaded with bioactive cues that prime endogenous cells to perform tissue-specific functions is utilized. In addition, immune-interactive biomaterials to proactively modulate the inflammatory response towards tissue healing, integration, and regeneration is also investigated. In addition, we are also developing target-specific biomaterials for cellular reprogramming to stimulate the tissue regeneration process. We expect that leveraging the regenerative potential of the human body via the novel design of smart and responsive biomaterials provides a simple and effective approach to replace injured or diseased tissues.

Reference: AK Gaharwar, I Singh, A Khademhosseini "Engineered biomaterials for in situ tissue regeneration", Nature Reviews Materials, 1-20

Omics-based Approaches for Bioengineering

Recent emergence in “omics” techniques providing readouts of different biological states, has allowed us to understand complex biological interactions of biomaterials and biomedical devices. Specifically, various genome wide assays capturing information about changes in mRNA levels to assessing changes in genomic accessibility have laid down the necessary foundation to provide an unbiased global view of the cellular activity with pivotal insights about the affected cellular pathways. Here, we propose to utilize transcriptomics, high throughput sequencing of expressed transcripts (RNA-seq), to provide a holistic view of the effect of biomaterials on the cellular gene expression program. RNA-seq is a powerful tool for an accurate quantification of expressed transcripts that largely overcomes limitations and biases of microarrays. The cell-biomaterials interactions are examined by monitoring transcriptome dynamics to uncover key biophysical and biochemical cellular pathways. Our approach further identifies enriched gene ontology (GO) pathways and categories related to key cellular functions.

More generally, transcriptomic analysis by next-generation sequencing provides a comprehensive and objective snapshot of cellular behavior following biomaterial exposure/attachment. Overall, our approach demonstrates the utility of next generation sequencing methods for the study of cellular interactions on bioengineered materials and the role this approach is likely to play in this rapidly expanding field of regenerative engineering.

Additive Biomanufacturing of Anatomical-Size Human Organs

Three-dimensional (3D) bioprinting is emerging as a promising method for rapid fabrication of biomimetic cell-laden constructs for tissue engineering using cell-containing hydrogels, called bioinks, that can be crosslinked to form a hydrated matrix for encapsulated cells. However, extrusion based 3D bioprinting has hit a bottleneck in progress due to the lack of available bioinks with high printability, mechanical strength, and biocompatibility. Our lab has introduced multiple approaches to design highly printable bioink for fabricating large scale, cell-laden, bioactive scaffolds. Specifically, we have introduced a range of bioink formulation consisting of nanoengineered bioinks, ionic-covalent entanglement (ICE) bioinks and nanoengineered ionic-covalent entanglement (NICE) bioinks with excellent printability, mechanical properties, and shape-fidelity.

Reference: Chimene D, Kaunas R, Gaharwar AK, Hydrogel Bioink Reinforcement Techniques for Additive Manufacturing: A Focused Review of Emerging Strategies. Advanced Materials (2020) 32 (1) 1902026

Inorganic Biomaterials for Regenerative Medicine and Drug Delivery

Conventional therapeutic strategies for regenerating damaged tissues rely on exogenous delivery of growth factors at very high concentrations that may lead to various complications such as uncontrolled tissue growth, inflammation, and tumorigenesis. These adversely limit the use of growth factors for therapeutic applications while simultaneously increasing up the cost of treatment. Using the mineralomics approach, our lab is working on the development of mineral-based nanoparticles which can substitute the growth factors. We investigate the effect of different biologically relevant minerals on mesenchymal stem cells and the changes that they induce right from the functional level to genetic levels. We want to leverage our findings to develop mineral-nanoparticle systems that can be used to selectively regenerate specific tissues without the need for any exogenous growth factors. Our current research focuses on regenerating bone and cartilage tissue but we hope to expand our search and apply them to regenerate more complex tissues such as neural and cardiovascular. We firmly believe that a comprehensive understanding of the molecular pathways regulated by the usage of minerals will radically alter the current growth-factor based approach to repair and regenerate damaged tissue and set the path towards more economically feasible and controlled strategies in the field of regenerative medicine.


Reference: Brokesh AM, Gaharwar AK. Inorganic Biomaterials for Regenerative Medicine Cite this: ACS Appl. Mater. Interfaces 2020, 12, 5, 5319–5344