Indiana Center for Regenerative Medicine and Engineering

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Wound, Burn, and Inflammation Program

In the United States, among patients with diabetes, 15 percent develop a foot ulcer, and 12 to 24 percent of individuals with a foot ulcer require amputation. With funding (1U01DK119099-01) from the National Institutes of Health, the Center for Regenerative Medicine and Engineering at Indiana University School of Medicine is able to treat diabetic foot ulcer with leading expertise.

The center is equipped with an interdisciplinary research and education program that delivers cutting-edge innovation that leads to the development of a Clinical Research Unit (CRU). The Center for Regenerative Medicine and Engineering is the major participant in this multi-site research consortium, focused on propelling new scientific discoveries to be expeditiously translated to better care for patients with diabetic foot ulcers.

The center is focused on providing wound-healing expertise and wound care of patient populations with diabetic foot ulcers. Using an efficient clinical and scientific infrastructure, the center is developing evidentiary criteria for qualifying/validating the targeted diabetic foot ulcer biomarker. Research faculty are developing and implementing novel strategies to monitor and address the confounding factors relevant to biomarker study outcomes. The center will establish Clinical Research Unit administration and achieve Diabetic Foot Consortium (DFC) readiness.

Burn and Biofilm Infection

When the barrier function of the skin is breached during burn wound, microbial infection colonizes the injured area. Microbial infestation leads to compromised host response to injury. The Center for Disease Control and National Institutes of Health estimate that more than 65 percent of all human infections caused by microbes exhibit a biofilm phenotype.

Pathogenic biofilms are microbial communities within self-secreted extracellular polymeric substance (EPS) collectively made up of carbohydrates, microbial proteins and DNA along with host substances. Such physical protective barrier confer antibiotic tolerance to microbes, thereby giving benefit to biofilm over planktonic form. This gives biofilms a more resistant version of infection and generates a potential candidate for antimicrobial strategies.

At the Center for Regenerative Medicine and Engineering, research efforts are focused on targeting molecular pathways to retard biofilm-inducible pathological mechanisms.

Roy S, Santra S, Das A, Dixith S, Sinha M, Ghatak S, Ghosh N, Banerjee P, Khanna S, Mathew-Steiner S, Ghatak PD, Blackstone BN, Powell HM, Bergdall VK, Wozniak DJ, Sen CK. (2019). Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen. Ann Surg.

Roy S, Elgharably H, Sinha M, Ganesh K, Chaney S, Mann E, Miller C, Khanna S, Bergdall VK, Powell HM, Cook CH, Gordillo GM, Wozniak DJ, Sen CK1. (2014). Mixed-species biofilm compromises wound healing by disrupting epidermal barrier function. J Pathol, 331-343.

Inflammation

Inflammation is a self-protecting immune response of the body against harmful stimuli in an attempt to eliminate the stimuli and initiate the healing cascade. Inflammation is essentially a beneficial response that normally resolves with the restoration of normal tissue homeostasis. However, when inflammation persists and becomes chronic inflammation, it can cause tissue damage and loss of function.

Non-resolving inflammation contributes significantly to the pathogenesis of a wide array of disorders, including atherosclerosis, obesity, cancer, chronic obstructive pulmonary disease, asthma, inflammatory bowel disease, neurodegenerative disease, multiple sclerosis and rheumatoid arthritis. Dysregulated inflammatory response leads to non-resolving chronic wounds, which represent a major and increasing socioeconomic threat affecting more than 6.5 million people in the United States, costing in excess of US $25 billion annually.

The primary focus of the inflammation research group at IU School of Medicine’s Center for Regenerative Medicine and Engineering is studying the significance and mechanisms of resolution of inflammation in the tissue repair and regeneration. Specifically investigators are interested in the role of macrophages in resolution of inflammation during pathological tissue repair such as diabetic wound healing. The center uses state-of-the-art technologies, such as laser capture microdissection and microarray expression (mRNA and miRNA) profiling, to address these research questions.

Imaging

High resolution imaging of cellular structure during reprogramming is the cornerstone for translation of regenerative engineering to clinical settings. A majority of available techniques to study regenerative tissue is extensively dependent on histochemistry/immunofluorescence and non-invasive strategies, such as PET, ultrasound, MRI and CT. The imaging core at The Indiana Center for Regenerative Medicine and Engineering houses a fleet of best-in-class imaging systems in the United States, including the latest generation of super resolution “airyscan” confocal systems.

Health outcomes imaging work within the center includes thermal imaging, Hitachi Noblus Versatile Ultrasound Machine, and GE Logiq E9 Ultrasound.

Laboratory imaging in the center includes Zeiss LSM 880 with Airyscan, Axio Scan 2.1, Dissection microscope, Laser speckle imaging, and Laser capture microdissection for genomics and proteomics study.