Improving the safety and effectiveness of adhesion prevention following colorectal procedures with high risk of cancer or infection

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Project Summary The leading cause of long-term post-operative morbidity is adhesions—which form in nearly 95% of patients following surgery. Adhesions are bands of scar tissue that contribute to the manifestation of myriad life-long complications (e.g. small bowel obstruction, infertility, and chronic pain). The annual healthcare burden from adhesions exceeds $3 billion, but options to mitigate adhesion formation are limited and flawed. Among all abdominal surgeries, the highest rate of adhesion-related complications occurs in colorectal surgery. While pathologies caused by adhesions may take months or even years to manifest clinically, colorectal surgery is also often complicated by infection (e.g., abscess formation or sepsis) and cancer tumorigenesis. The objective of this proposal is to determine the effect of our newly developed sprayable hydrogel technology for adhesion prevention in colorectal surgery within high risk surgical environments contaminated by bacteria or cancer cells. TYBR’s expertise in biomaterial development and fluid dynamics has informed the development of a sprayable adhesion barrier derived from extracellular matrix (ECM Spray), which serves as a mechanical barrier that elicits a healing response from the patient’s own body to prevent adhesions and regulate tissue repair. The ECM Spray is thermally responsive and (upon contact with tissue) forms a thin film hydrogel to prevent adhesions between adjacent tissues by acting as a mechanical barrier. ECM Spray has proven to be >75% effective at reducing the incidence and tenacity of adhesions in well-accepted small and large animal surgical models. These promising, data show effective adhesion reduction with ECM Spray where sterility is maintained, but it is unknown how ECM Spray will perform in contaminated surgeries—an at risk patient population without an effective therapy because competitor products are largely contraindicated for use in contaminated surgeries. Infection risk is a key translational challenge for adhesion barriers, which has been highlighted by past failed products, including Intergel which was removed from the market after over 100 reports of infection problems, including 3 deaths. Therefore, the objective of the present study is to determine if ECM Spray will prevent adhesion formation without increasing risk of tumorigenesis or abdominal abscess in a contaminated surgeries. In Aim 1, we will determine the effect of ECM Spray on bacterial growth. In Aim 2, we will determine the effect of ECM Spray on cancer tumorigenesis. Results of the proposed work will directly lead to a key research and development milestone towards commercialization. These results will be presented to the FDA to establish safety and efficacy of ECM Spray for use in tumor resection surgeries and non-sterile surgeries and increase the technological and commercial potential of ECM Spray. In addition, if we show potential for ECM Spray to reduce infection, this will broaden the scope for use and dramatically increase the patient and clinical impact, as well as encourage surgeon adoption in surgeries with a contaminated field.