This Small Business Innovation Research (SBIR) Phase I project proposes to develop a novel biomimetic adhesive for seroma prevention. Commercial bioadhesives have demonstrated mixed results as they are hampered by weak adhesive strengths, the need to mix precursors, and undesirable degradation rates. Thus, there continues to be an unmet clinical need for the development of a new and improved adhesive for seroma prevention. Nerites Corporation has developed adhesives that are synthetic mimics of the mussel adhesive proteins that can bind strongly to rocks and ship hulls in a wet, turbulent saline environment. Nerites? new series of adhesives requires no mixing or dissolution before use, and demonstrates significantly higher strength than currently available adhesives. Therefore, Nerites believes that these new materials will significantly improve clinical outcomes of many patients suffering from seroma.
The broader/commercial impacts of this research are a potential reduction in seroma formation, a postoperative complication in many surgeries. Although the market for Nerites? adhesives may eventually expand to include any surgery where tissue planes are separated, the initial focus involves procedures where postoperative drains are the standard of practice. The benefits that result from reduced use of drains include increased patient comfort, shorter hospital stay, reduced chemotherapy duration, and decreased risk of wound infection. Therefore, Nerites? initially targeted surgical procedures include mastectomy, abdominoplasty, and open ventral hernia repair, with a combined estimate of more than 500,000 surgeries performed annually, where incidences of seroma formation can be as high as 59%.
PI: Bruce Lee Award Number: 1153345 Seroma formation is common after any surgery involving elevating skin flaps or creating potential space between adjacent layers of tissue. A seroma forms when a "pocket" of dead space fills with serous fluid. Untreated seromas can lead to serious complications including skin flap necrosis, delayed wound healing, extended hospital stays, and added health costs. Seroma formation is especially common after mastectomy. While there are many diverse methods to prevent post-surgery seroma formation (surgical techniques, pressure dressings, sclerosing agents, closed drain suction devices), no ideal method and/or product has yet been developed. One promising treatment option is using tissue adhesives to eliminate dead space. The ideal tissue adhesive should be easily delivered and applied, biocompatible, strong yet compliant, degrade at an appropriate rate for allowing union of the specific tissues forming the dead space, and suitable for room-temperature storage. A literature review revealed the use of fibrin glues for seroma prevention in clinical and preclinical studies; however those glues have not consistently reduced seroma formation. Further, fibrin glues have weak adhesive strength, can potentially transmit disease, and require mixing the precursors immediately before use, which can complicate and extend surgical procedures. The goal of this SBIR Phase I project was to develop an adhesive that will overcome the various limitations of existing techniques for seroma reduction or prevention, and satisfy the urgent clinical need for an adhesive to prevent seroma formation. The novel technology utilized in this research project was inspired by the adhesive proteins secreted by marine mussels. Even in a wet, turbulent, saline environment, these adhesive proteins harden rapidly to enable marine mussels to anchor themselves to various surfaces. One interesting component of these adhesives is 3,4-dihydroxyphenylalanine (DOPA), an amino acid that is responsible for both the moisture-resistant adhesion and cohesive hardening of these adhesive proteins. This adhesive moiety was incorporated into a synthetic, biocompatible and biodegradable adhesive film, which demonstrated significantly higher adhesive strength compared to fibrin glue. The performance of the adhesive film can be easily tailored by various factors such as film thickness, chemical architecture, and the composition of the films. The degradation rate of the adhesive can be tuned between days to months depending on the need of the application. These adhesive films were used to close the dead space between tissue layers in a rat mastectomy model and compared to a saline control. Serous fluids were aspirated on days 7, 14 and 21 and the incidences of seroma were recorded. Adhesive-treated groups demonstrated a slight decrease in the incidences of seroma when compared to the control, which resulted in seroma 100% of the time. Although the adhesive-treated groups demonstrated a slight decrease in the frequency of seroma by day 21, when seromas did form there was no significance difference in terms of the volume of aspirated fluid between test groups. Histological analysis demonstrated no difference among the test groups based on seroma capsule thickness, amount of peripheral granulation tissue and inflammatory responses. This result indicated that the adhesive films did not adversely affect the healing process and were biocompatible. Overall, it was concluded that these adhesive films did not adequately prevent seroma formation. This may attributed to the poor reproducibility of the animal model as the total serous fluid collected for the control group was lower than reported in the literature. Future study may involve testing these adhesives in a more reliable model.
