Micro-Shield: Abdominal Adhesion Prevention

Highlights

• Abdominal adhesions are an unintended consequence of abdominal surgery and can cause small bowel obstructions.
• Small bowel obstructions lead to 15% of surgical hospital admissions, 300,000 operations per year, and $2.3 billion per year.
• Micro-Shield is a novel therapeutic to prevent the formation of adhesions that lead to small bowel obstructions.
• Recipient of $100,000 PInCh Award + $15,000 Bonus Award for Engineering Good Health.

Problem

Over 3 million major abdominal surgeries are completed every year in the United States. Small bowel obstructions, or bowel blockages, are a significant and common complication of any major abdominal surgeries. They account for ~15% of surgical hospital admissions every year and result in an excess of 300,000 operations, costing the healthcare system $2.3 billion.

The vast majority of bowel obstructions are caused by surgical adhesions, which are fibrous scars that form during the healing process after any major abdominal surgery. Surgical adhesions can also cause chronic abdominal pain, infertility, and distort normal anatomy thereby increasing the risk of complications from any future abdominal surgeries.

Small bowel obstructions are treated with nasogastric tubes to physically decompress the stomach and typically require a 4-5 day hospital admission. However, 15% of patients will require another operation to resolve a small bowel obstruction. While surgery is effective in treating an acute bowel obstruction, it is a double-edged sword in that the surgery will treat the prior adhesions but result in the formation of new adhesions.

There are currently no effective methods to prevent adhesive small bowel obstructions, creating a need for an innovative solution.

Solution

Currently, few commercially available products reduce adhesion formation and prevent small bowel obstructions. The most popular product is a solid film barrier that is used to physically wrap the abdomen, acting purely as a bioabsorbable mechanical barrier without any effect on the underlying biology of adhesion formation. Clinical studies have shown that it is not effective at preventing bowel obstructions.

Micro-shield is a novel microparticle-based system to inhibit the formation of abdominal adhesions by temporarily inhibiting the cells that are key in creating adhesions. The microparticles are a biodegradable system that will dissolve over the course weeks and release inhibitory medication as it degrades. In comparison to the commercially available competition, our product will be able to target a higher surface area in the abdomen, increasing its efficiency, and promote easier use by the physician. The polymers used are inert and prove to be safe in multiple FDA approved devices in the past.

Based on our team’s expertise in polymers and drug release, we have been able to fine-tune the system in terms of dissolution rate and duration of drug release. We have at this stage created and started optimization of release profiles of our microparticle system. Additionally, we have started preliminary mouse studies to study effectiveness in a pre-clinical model. 

Team

• Steven Little, PhD is a Distinguished Professor and Chair of the Department of Chemical and Petroleum Engineering with significant expertise in the field of drug release and biomaterials.
• Matthew R. Rosengart, MD, MPH is the Watson Family Professor of surgery and critical care medicine at UPMC, clinically active trauma surgeon, and a basic scientist at the University of Pittsburgh.
• Thiagarajan Meyyappan, MD is a 4^th year general surgery resident at UPMC. In addition to his clinical background, he has a background in biomedical engineering and served as the lead design engineer for an early-stage biotech start-up.

Path to Impact Plan

As a result of the PInCh award, our team will be able to complete our microparticle optimization and animal studies. Specifically, we will develop our polymer microparticle system for the release of adhesion inhibitors. We will then test these microparticles both for efficacy in a mouse model of intra-abdominal as well as their effects on wound healing for intestinal anastomosis and fascial/skin healing.

Once experiments for efficacy in a pre-clinical model are completed, we will plan for a new spin-out company founded by the core team members. The company will plan to license the provisional patent (once filed) from Pitt then seek an NIH SBIR loan as well as raise an angel round of investments.

Our clinical trial design will focus on rectal cancer patients who are treated with planned two stage operations. With the planned two stage operation, we will placebo or micro-shield at the time of the first operation to the control and experimental groups, respectively. During the second planned operation 3 months later, we will have blinded surgeons grade the severity of adhesions noted.

Frequently Asked Questions

• Are there opportunities for other applications where this could be relevant?
  Post-operative adhesions causes significant complications in a number of surgical fields, including thoracic, vascular, Ob/Gyn, and orthopedic surgery. For example, adhesions after gynecological procedures are a significant cause of infertility leading to additional surgeries to remove the adhesions. Once validated in general surgery, we will explore these additional fields.
  
• How will the micro-shield system inhibit adhesions without affecting wound healing for your incisions or anastomoses?
  Our microparticle delivery system will allow for effective local concentrations of medication with negligible systemic absorption. This localized and short-term release of medication will assist in limit adhesions but should not be in high enough concentration or duration to affect wound healing.