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:

Responsive Biomaterials for In Situ Tissue Regeneration

Nanomaterials have been extensively investigated for delivery of therapeutics to cells and tissues for regenerative medicine, stem cell engineering, immune modulation, and cancer therapeutics. By modulating the physiochemical characteristics of nanoparticles, therapeutic efficacy, cellular internalization, biodistribution, and in vivo retention can be customized. Our lab is interested in developing developing two-dimensional (2D) nanomaterials for therapeutic delivery and tissue engineering. 2D nanomaterials are ultrathin nanomaterials with a high degree of anisotropy and chemical functionality. We are synthesizing a range of 2D nanomaterials various 2D nanoparticles such as nanosilicate, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs) and introducing it to biomedical community by designing smart, responsive and adaptive structures that can be used for regenerative medicine, drug delivery and immunomodulation.

Omics-based Approaches for Regenerative Medicine (Materialomics)

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.

Mineralomics: Understanding Role of Minerals in Regenerative Medicine

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

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