Reconstructive surgery with biomaterials is commonly used to repair musculofascial defects in the abdominal wall that result from traumatic injury or ventral hernia, the outcomes of which are worsened with ageing. Current reconstructive options in this arena are autologous tissue (fascial grafts or tissue flaps), which are limited in supply, synthetic materials such as polypropylene (PP mesh) that cause bowel adhesions, and naturally derived degradable extracellular matrix (ECM) scaffolds (acellular dermis, small intestine submucosa) that are animal or human derived, expensive, limited in size, and provide limited control of architecture per patient specific geometry or initial mechanical properties. We propose an alternative option to abdominal wall repair that involves engineering the microstructure, architecture, and mechanical properties of a biomimetic or biologically derived polymer system in order to improve the initial mechanical strength of the repaired mechanically-loaded host site and provide patient specific control of tissue regeneration at the same time. In order to strengthen the novelty of the proposed study, we plan to utilize the technique of dielectrophoretic assembly of SF fibers in 3-D SF-decorin scaffolds that allows us to facilitate the formation, size, and alignment of the SF fibrils. This novel methodology was developed in our laboratory in order to architect the 3-D design of SF based scaffolds. We hypothesize that the initial mechanical strength of the silk fibroin based scaffolds will increase with decorin due to the induction of fibril formation and would result in higher tensile strength of the regenerated tissue characterized by seamless integration at the repair site such that the integrity of the repair site is not compromised over the entire period of remodeling. We will evaluate this hypothesis by investigating the following specific aims.
Specific Aim 1. Fabricate fibrous scaffolds of SF-decorin using dielectrophoresis and compare and contrast the structure and mechanical properties.
Specific Aim 2. Study mechanistic interactions between SF and decorin using computational modeling and characterization techniques and assess the affect of degradation enzymes.
Specific Aim 3. Evaluate remodeling parameters and bowel adhesions after repair of the musculofascia with SF, SF-decorin, and HADM for 1, 2, 4 weeks, and 3 months in an in vivo guinea pig model.
Reconstructive surgery with biomaterials is commonly used to repair musculofascial defects in the abdominal wall that result from traumatic injury or ventral hernia, the outcomes of which are worsened with ageing. Current reconstructive options in this arena are autologous tissue (fascial grafts or tissue flaps), which are limited in supply, synthetic materials such as polypropylene (PP mesh) that cause bowel adhesions, and naturally derived degradable extracellular matrix (ECM) scaffolds (acellular dermis, small intestine submucosa) that are animal or human derived, expensive, limited in size, and provide limited control of architecture per patient specific geometry or initial mechanical properties. We propose an alternative option to abdominal wall repair that involves engineering the microstructure, architecture, and mechanical properties of a biomimetic or biologically derived polymer system or an Engineered Biologic in order to improve the initial mechanical strength of the repaired mechanically-loaded host site and provide patient specific control of tissue regeneration at the same time without compromising the mechanical integrity of the repaired site during the remodeling process.
| Dunne, Lina W; Iyyanki, Tejaswi; Hubenak, Justin et al. (2014) Characterization of dielectrophoresis-aligned nanofibrous silk fibroin-chitosan scaffold and its interactions with endothelial cells for tissue engineering applications. Acta Biomater 10:3630-40 |
