Research Areas

Salivary Gland Regeneration

Conjunctival and Lacrimal Gland Regeneration

Restoration of the Eccrine & Apocrine Sweat Glands

Skin Tissue-Engineering

Research Interests

Dr. Pradhan-Bhatt’s research focuses on tissue engineering of soft tissues and glandular organs. Her research involves the use of biomedical engineering principles to study and recreate organ systems from the molecular and cell level. Her work involves studying the behavior of primary cells in 3D biomimetic material scaffolds by dialing in unique biological cues. Her work also utilizes surgical expertise to determine the best techniques to implant a neo-tissue/organ that can be functional in an animal model.

Dr. Pradhan-Bhatt’s current projects include salivary gland tissue engineering, lacrimal gland regeneration and engineering of the eccrine and apocrine sweat glands of the skin in efforts to make artificial skin equivalents.

Salivary Gland Tissue Engineering

Dr. Pradhan-Bhatt and Dr. Robert Witt, chief of the Multidisciplinary Head and Neck Oncology Center at the HFGCCRI, are working toward the creation of artificial salivary glands, a breakthrough that will ultimately provide relief for tens of thousands of patients who can no longer produce saliva as a result of radiation treatment for upper-respiratory cancer. Over 40,000 US cancer patients are affected annually by xerostomia after head and neck irradiation. Loss of salivary gland function impairs oral health and reduces life quality. Our goal is to restore salivary gland function using human salivary progenitor cells reconstituted in modular hydrogel form into patients with xerostomia. A hyaluronic acid (HA) based matrix-modified modular hydrogel culture system that fosters growth and differentiation of human parotid gland progenitor cells into functional structures has been established. Efforts to differentiate these structures into complete branched architectures that resemble the native gland are underway. Additional work involves induction of angiogenesis and neurogenesis into the engineered implants to ensure long-term survival and obtain complete functionality of the implant. Work with animal models has been initiated for biocompatibility and preliminary functionality studies.

This interdisciplinary project involves a multi-disciplinary team of biologists, clinicians, bioengineers, and material scientists. Our collaborators include Dr. M. Cindy Farach-Carson from Rice University, Dr. Xinqiao Jia from Materials Sciences & Engineering at the University of Delaware, Dr. Matthew Hoffman from the National Institute of Dental & Craniofacial Research (NIDCR) at the NIH and Dr. Michael Passineau from the Alleghany General Hospital.

Lacrimal Gland / Conjunctival Tissue-Engineering Project

Radiation therapy used to treat patients suffering from upper respiratory cancer can also lead to xerophthalmia due to damage to the secretory cells of the lacrimal glands. Xerophthalmia, also known as dry eye syndrome or keratoconjunctivitis is a chronic condition that affects close to 10 million people in the United States. In addition to radiotherapy, this condition can be caused by several autoimmune disorders including Sjogren’s syndrome, Steven-Johnson’s syndrome and ocular cicatrical pemphigoid, all of which result in damage to the secretory cells of the lacrimal gland and lead to dry eye syndrome (DES). Severe DES can lead to ocular surface inflammation, damage to the conjunctiva, followed by ocular epithelial damage and corneal ulceration that can eventually lead to loss of vision. A tissue-engineered functional lacrimal gland can provide an effective solution to restore tear fluid. Our extensive experience in salivary gland tissue engineering will aid our efforts in generating a functional lacrimal gland. In addition to the lacrimal glands, we are also working on engineering conjunctival tissue, which is damaged due to extreme DES.

Skin/Eccrine & Apocrine Sweat Gland Engineering Project

There is an immense clinical need for reconstructed skin equivalents to benefit patients suffering from severe burn injuries. Treatment of burn wound care has been shifted from merely achieving satisfactory survival rate to improvement in the long-term form and function of the healed burn wounds and improved quality of life. Timely restoration of skin protective functions is key to the successful treatment of burn victims. Many of the reconstructed skin models currently on the market, still lack skin appendages. The sweat glands are one of the major skin appendages, which play a crucial role in temperature regulation and maintenance of homeostasis. This project aims to engineer artificial skin along with appendages such as the eccrine and apocrine sweat glands, in vitro, which can be embedded into the dermis of reconstructed skin and thus, create a more complete equivalent of native human skin. Current work has led to the development of a dissociative and non-dissociative model of the epidermis, which can be used for in vitro toxicology testing.

Patents

Implantable Modular Hydrogel for Salivary Gland Restoration, 61/576,721

Selected Publications

Summary of published work: https://www.researchgate.net/profile/Swati_Pradhan-Bhatt

Complete list of publications: http://www.ncbi.nlm.nih.gov/sites/myncbi/1ZisfryYlEbAV/bibliography/47447059/public/?sort=date&direction=ascending

Pradhan S, Zhang C, Jia X, Witt R, Farach-Carson, MC. (2009) Perlecan domain IV peptide stimulates salivary gland cell assembly in vitro. Tissue Eng Part A. 15(11): 3309-20.

Pradhan S, Liu C, Zhang C, Jia X, Farach-Carson MC, Witt R. (2010) Lumen Formation in 3D cultures of salivary acinar cells. Otolaryngology-Head and Neck Surgery. 142(2): 191-5.

Pradhan S, Farach-Carson MC. (2010) Mining the Extracellular Matrix for Tissue Engineering Applications. Regenerative Medicine. 5(6): 961-70.

Pradhan-Bhatt S, Harrington DA, Duncan RL, Jia X, Witt RL, Farach-Carson MC. (2013) Implantable Three-Dimensional Salivary Spheroid Assemblies Demonstrate Fluid and Protein Secretory Responses to Neurotransmitters. Tissue Eng Part A. 19(13-14):1610-20.

Pradhan-Bhatt S, Harrington DA, Duncan RL, Jia X, Farach-Carson MC, Witt RL. (2013). A novel in vivo model for evaluating functional restoration of a tissue-engineered salivary gland. Laryngoscope. 124(2): 456-61.

Dicker K, Gurski L, Pradhan-Bhatt S, Witt RL, Farach-Carson MC and Jia X. (2013) Hyaluronan: A Simple Polysaccharide with Diverse Biological Functions. Acta Biomaterialia. 10(4): 1558-70.

Pradhan-Bhatt S, Cannon K, Zakheim D, Harrington DA, Duncan RL, Jia X, Farach-Carson MC, Witt RL, “Salivary Gland Tissue Engineering and Repair” in Stem Cell Biology and Tissue Engineering in Dental Sciences, ed. Vishwakarma A; Sharpe, P; Shi, S; Ramalingham, M; 2014, Elsevier.

Forrest A, Kawaji H, Rehli M, Baillie JK, de Hoon M, Haberle V, Lassmann T, Kulakovskiy IV, Lizio M, Itoh M, Andersson R, Mungall CJ, Meehan TF, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schmidl C, Schaefer U, Medvedeva YA, Plessy C, Vitezic M, Severin J, Semple CA, Ishizu Y, Francescatto M, Alam I, Albanese D, Altschuler GM, Archer J, Arner P, Babina M, Baker S, Balwierz PJ, Beckhouse A, Pradhan-Bhatt S et al. (2014) A promoter level mammalian expression atlas. Nature. 507(7493): 462-70.

Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, Ntini E, Arner E, Valen E, Li K, Schwarzfischer L, Glatz D6, Raithel J, Lilje B, Rapin N, Bagger FO, Jørgensen M, Andersen PR, Bertin N, Rackham O, Burroughs AM, Baillie JK, Ishizu Y, Shimizu Y, Furuhata E, Maeda S, Negishi Y, Mungall CJ, Meehan TF, Lassmann T, Itoh M, Kawaji H, Kondo N, Kawai J, Lennartsson A, Daub CO, Heutink P, Hume DA, Jensen TH, Suzuki H, Hayashizaki Y, Müller F; Pradhan-Bhatt S and FANTOM Consortium, Forrest AR, Carninci P, Rehli M, Sandelin A. (2014) An atlas of active enhancers across human cell types and tissues. Nature. 27;507(7493):455-61.

Harrington DA, Martinez M, Wu D, Pradhan-Bhatt S, Farach-Carson MC. (2015) “Salivary Gland Tissue Engineering and Future Diagnostics” in Advances in Salivary Diagnostics, ed. Streckfus CF. Springer Berlin Heidelberg, 157-185.

Hubka KM, Wu D, Harrington DA, Langer JC, Pocard T, Jammayrac O, Farach-Carson MC, Pradhan-Bhatt S. (2015) Dissociative and non-dissociative models for culture of human eccrine glands for toxicology testing and tissue engineering applications. Applied In Vitro Toxicology. 1(3): 187-197.

Pradhan-Bhatt S, Witt RL. (2015) Tissue Engineering a Salivary Gland, In Marchal F.ed Sialendoscopy. 92-94.