(659b) Injury Biomechanics-Guided Soft Tissue Engineering Using Regenerative Biomaterials

Annually, 30 million Americans seek medical treatment for injuries amounting to approximately 700 billion dollars in medical and work-loss related costs. After an injury, inflammatory cells infiltrate the injury site to clean-up dead cell debris during the acute inflammatory phase of tissue repair. Later these cells facilitate lost tissue regeneration by directing stromal cells to secrete extracellular matrix (ECM) and promote remodeling of the damaged ECM to allow for new cellular connections to be made. However, rapid accumulation of disorganized ECM and incomplete remodeling can result in distorted tissue architecture (fibrosis or scar formation), which can hinder tissue function. The early phase of inflammation and the late phase of remodeling are potential intervention points to minimize aberrant ECM deposition and promote tissue regenerative and functional outcomes.

As an Assistant Professor, I plan to establish an innovative research program that will converge fundamental tissue-mimetic in vitro models of injury, repair, and regeneration with insight-driven therapeutic biomaterial development and testing in translational animal models in vivo. Specifically, I will (A) design and develop biologically detailed models of soft and complex tissue injury, fibrosis, and remodeling in vitro, which will assist in regenerative biomaterial design, drug screening, and patient-specific diagnostics. With in vitro models, I aim to identify novel drug targets that will respond to personalized biological cue-based “cell-instructive” biomaterial-based therapy for translational benefit upon controlled biomechanical injury. In concert, I will (B) engineer soft and complex tissue regeneration via the implantation of the designed therapeutic biomaterials in relevant pre-clinical models of tissue injury.

Research Experience

To realize the potential of biomaterials as powerful tools to modulate the tissue-repair processes, I began my graduate research training in the Department of Bioengineering at Clemson University studying the protein-biomaterial surface interactions that influence cellular response to implanted biomaterials. With this experience, I was able to establish a 3-D in vitro model of brain tissue during my doctoral education in Bioengineering in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. Using this model, I investigated cell-biomaterial, cell-ECM, cell-cell interactions, and cellular tolerance to traumatic brain injury (TBI).

I continued with postdoctoral work in the Department of Biomedical Engineering at Duke University, where I engineered immunomodulatory wound healing biomaterials that alleviated the foreign body response via directing immune cell migration and vascular network assembly. Most recently, I led a collaboration between the Department of Orthopaedic Surgery at UConn Health and the Novartis Institutes for BioMedical Research to improve the regeneration of complex tissues using development-associated morphogens and stem cell delivery in preclinical animal models. With this training, I can uniquely investigate the biomaterial-mediated tissue repair response from multiple-perspectives following defined biomechanical injury. My goal is to improve tissue-regenerative outcomes following musculoskeletal and neural injuries.

Selected Publications (17 in total, accrued 1000+ citations as of June 2021)

• Prabhath, V.N. Vernekar *, V. Vasu, M. Badon, J.-E. Avochinou, A.D. Asandei, S.G. Kumbar, E. Weber, and C.T. Laurencin, “Kinetic degradation and biocompatibility evaluation of polycaprolactone-based biologics delivery matrices for regenerative engineering of the rotator cuff,” Journal of Biomedical Materials Research: Part A, 11 May 2021 (* co-first author)
• V.N. Vernekar and M.C. LaPlaca, “3-D Multi-Electrode Arrays Detect Early Spontaneous Electrophysiological Activity in 3-D Neuronal-Astrocytic Co-Cultures,” Biomedical Engineering Letters, 2020, 1-13
• V.N. Vernekar, R. James, K.J. Smith, C.T. Laurencin, “Nanotechnology Applications in Stem Cell Science for Regenerative Engineering,” Journal of Nanoscience and Nanotechnology, A Special Issue on “Role of Nanotechnology in Stem Cell Research,” M. Ramalingam, A. El Haj, T. Webster, S. Ramakrishna (Editors), 2016, 16: 8953-8965
• J. Killian, V.N. Vernekar, S.M. Potter, J. Vukasinovic, “A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In Vitro," Frontiers in Neuroscience, 2016, 10: 135
• Kasir, V.N. Vernekar *, C.T. Laurencin, “Regenerative Engineering of Cartilage Using Adipose-Derived Stem Cells,” Regenerative Engineering and Translational Medicine, 2015, 1: 42-49 (* co-first author)
• V.N. Vernekar, C.S. Wallace, M. Wu, J. Chao, S. O'Connor, A. Raleigh, A.X. Liu, J.M. Haugh, W.M. Reichert, “Bi-Ligand Surfaces with Oriented and Patterned Protein for Real-Time Tracking of Cell Migration,” Colloids and Surfaces: B, 2014, 123: 225–235
• K. Cullen, V.N. Vernekar, M.C. LaPlaca, “Trauma-Induced Plasmalemma Disruptions in Three-Dimensional Neural Cultures Are Dependent on Strain Modality and Rate,” Journal of Neurotrauma, 2011, 28: 2219-2233
• V.N. Vernekar, D.K. Cullen, N. Fogleman, Y. Choi, A.J. García, M.G. Allen, G.J. Brewer, M.C. LaPlaca, “SU-8 2000 Rendered Cytocompatible for Neuronal BioMEMS Applications,” Journal of Biomedical Materials Research, 2009, 89: 138-151
• V.N. Vernekar and R.A. Latour, “Adsorption Thermodynamics of a Midchain Peptide Residue on Functionalized SAM Surfaces using SPR,” Materials Research Innovations, 2005, 9: 53-55

Research Proposal Experience

In addition to my research expertise, I have acquired hands-on experience with grant proposal writing by assisting mentors in developing and revising grant proposals to successfully acquire funding including through the NIH R01, NSF AIR, and SBIR funding mechanisms.

Postdoctoral Projects

“Tendon-to-Bone Enthesis Regeneration via an Engineered Morphogen Delivery Matrix”

“Rapid and Non-Enzymatic Adipose-Derived Stem Cell Isolation and Delivery for Cartilage Regeneration”

Supervised by Professors Cato T. Laurencin, M.D., Ph.D. and Sangamesh G. Kumbar, Ph.D., Department of Orthopaedic Surgery, UConn Health, Farmington, CT

“Orientation and Patterning of Chemokine and Cell Adhesion Molecules on Biomaterial Surfaces to Direct Immune Cell Migration”

“A Wound Healing Promoting Biomaterial Sleeve around Implantable Glucose Biosensors”

Supervised by Professor W. Monty Reichert, Ph.D., Department of Biomedical Engineering, Duke University, Durham, NC

Doctoral Dissertation

“Optimization of 3-D Neural Culture and Extracellular Electrophysiology for Studying Injury-Induced Morphological and Functional Changes”

Supervised by Professor Michelle C. LaPlaca, Ph.D., Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA

Teaching Interests

I am interested and qualified to teach both Chemical Engineering and Bioengineering courses at the undergraduate and graduate levels in the areas of biomaterials, thermodynamics, fluid mechanics, and biomechanics. Additionally, I am excited to create a graduate/elective course in the emerging fields of drug delivery, tissue engineering, regenerative medicine, neural engineering. I will include a combination of hands-on learning through laboratory-based projects as well as reading the current literature for students to inspire discussion of underlying theories and techniques in these areas.

As an example, my tissue engineering course will be a combination of both lectures and laboratory sessions. The lectures will focus on the application of cell biology, biomaterials, and chemical engineering principles in the design of engineered constructs for different types of tissues such as bone, cartilage, nerves, etc. They will also introduce the students to relevant topics including drug delivery, molecular engineering, cellular engineering, pre-clinical testing in animal models, etc. Students will also have an opportunity to practice in laboratory sessions, scaffold fabrication and characterization, tissue culturing and imaging, bioreactor-based tissue fabrication, etc.

Teaching Experience

I have demonstrated my ability to teach in both classroom and laboratory settings over a wide range of subjects at the undergraduate and graduate levels. My formal pedagogical training began at the University of Pune in India as a Lecturer helping build a new Chemical Engineering program. There I earned university-level teacher’s induction training certification and prepared the teaching materials and taught the core courses of Mechanical Operations, Mass Transport, Thermodynamics, Reaction Engineering, and associated labs to upper-level undergraduate students.

Later during my master’s education at Clemson University, I co-taught and graded the junior-level Engineering Materials course and designed and implemented a lab-module for a graduate-level Molecular Bioengineering course. I continued to teach during my doctoral studies at Georgia Tech as a teaching assistant (TA) for the Quantitative Engineering Physiology Lab. This course had an extraordinary teaching strategy whereby student teams were allotted limited resources to independently solve engineering problems in the face of technical challenges. As TA, I helped students to trouble-shoot problems whenever needed and graded their work. Most recently, I helped organize the teaching materials including problem sets for the upper-level undergraduate/graduate Drug Delivery course at the University of Connecticut as well as delivered a few lectures. These experiences have given me a better understanding on how to teach effectively.

Mentorship

Besides the formal teaching assignments, the opportunity to mentor students has been a formative experience in my training. I have had the privilege of mentoring diverse undergraduate, graduate, and medical students, including a couple junior postdocs in the laboratory. To date, nine of the students I have mentored have co-authored with me conference presentations, scientific publications, and have gone on to pursue graduate work at top institutions in the US, Europe, and India. I have encouraged and guided out-of-lab experiences including participation in student competitions. For example, I supervised the work of a diverse undergraduate team that won the 1^st place at the 2016 UConn Engineering School Senior Design Competition. Likewise, I have actively participated via mentoring to several undergraduate students as well as a high school teacher in summer Research Experience and Mentoring (REM) programs. These experiences have shaped me both as a research and educator, and have been one of the most rewarding aspects of my academic career thus far.