(531g) In Situ Deposition of Cellular Hydrogels for Treatment of Inflammatory Bowel Disease

Authors: 
Pehlivaner, M., Northeastern University
Ekenseair, A., Northeastern University
Lutkus, T., Northeastern University
In Situ Deposition of Cellular Hydrogels for Treatment of Inflammatory Bowel Disease

Meryem O. Pehlivaner1, Theodore Lutkus2, Adam K. Ekenseair1

1Department of Chemical Engineering, 2Department of Bioengineering

 Northeastern University, Boston, MA 02115, USA

Inflammatory bowel disease (IBD), most notably Crohnâ??s disease and ulcerative colitis, currently afflicts millions of patients worldwide and leads to chronic inflammation of all or part of the digestive tract and damage to the intestinal lining. Current treatment plans focus on systemic or intestinal delivery of drugs; however these drugs frequently fail or are inadequate to prevent or reverse the damage. Over the long term, patients will require surgery to remove diseased sections of their bowels [1-5]. The purpose of this study is to develop a new class of colonoscope-based treatment options that specifically target the diseased area and locally deliver drugs and stem cells through sprayable application of a regenerative hydrogel during diagnostic procedures. Thermo-responsive hydrogel solutions can solidify immediately on warm body tissue after spraying and create a homogeneous therapeutic coating on the diseased tissue. The hydrogelâ??s physical properties can be easily manipulated, and the use of spray deposition techniques will enable rapid and minimally-invasive application of homogenous, multilayer, and conformal coatings in vivo. Ultimately, the regeneration of diseased or damaged sections of the intestinal tract could prevent the need for bowel resection, lead to reduced symptoms, and provide a higher quality of life for patients.

In this study, poly(N-isopropylacrylamide)-based thermogelling and crosslinking polyamidoamine macromers were synthesized and combined to create a sprayable, in situ forming dual gelling hydrogel system for delivery of cellular hydrogel coatings onto warm tissues. The impact of spray technique, solution formulation, pressure, and viscosity on the viability of fibroblast cells encapsulated in hydrogels was investigated. Smooth, fast, and conformal hydrogel coatings were obtained when thermogelling macromers were sprayed with high polyamidoamine concentration at low pressure. Moreover, decreased early micronetwork formation, viscosity and pressure all improved cell viability in hydrogels. To further increase the survival rate of sprayed cells, a custom-designed airbrush was produced via 3D printing technology and viability of fibroblast cells in hydrogels was increased from 45% to 85%. Ex vivo tests showed that airbrush spraying is a versatile tool to create cellular hydrogel coatings onto intestinal tissue surfaces in less than a minute. The results demonstrated that sprayable, in situforming hydrogels capable of delivering cell populations on diseased tissues offer promise as novel therapies for regenerative medicine.

References

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[2] P.L. Lakatos, Recent trends in the epidemiology of inflammatory bowel diseases: up or down? World Journal of Gastroenterology 12 (2006) 6102.

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[5] C.N. Bernstein, A. Kraut, J.F. Blanchard, P. Rawsthorne, N. Yu, R. Walld, The relationship between inflammatory bowel disease and socioeconomic variables, Am. J. Gastroenterol. 96 (2001) 2117-2125.

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