UCLA

Soft tissue loss can be the result of many clinical issues. An engineered injectable material to stimulate soft tissue regeneration would be an improvement for many clinical applications within tissue augmentation including dermal augmentation, periurethral bulking, and gingival augmentation.

Implanted biomaterials are usually held to a standard of biocompatibility meaning that the overall goal for a biomaterial is to have it as inert as possible and to act stealthily when it comes in contact with the body. This is to avoid a chronic foreign body response and ultimately rejection of the biomaterial. The goal of this project was to utilize a mild, transient immune response within the soft tissue of the body to accelerate regeneration of the extracellular matrix proteins and therefore tissue augmentation.

An injectable biomaterial was utilized to increase the volume of the soft tissue, then it was combined with a bioactive coating that elicited an immune response. The injectable material was fabricated out of macroporous poly ε-caprolactone (PCL) microparticles and coated in the bioactive polymer, poly lactic co-glycolic acid (PLGA). The host-material interaction of the bioactive PLGA with biological cells was characterized in vitro by inflammatory cytokine production using a multiplex system. It was found that the co-culture of human fibroblasts and monocytes produced elevated levels of IL-1β, IL-6, GM-CSF, and TNF-α in response to the PLGA biomaterial. Subsequently, the cell infiltration, inflammatory response, blood vessel infiltration, and collagen deposition were analyzed to determine tissue regeneration and healing in vivo. The murine model showed more thorough tissue integration and healing with added porosity and bioactive PLGA coating through blood vessel infiltration and extracellular matrix deposition. The accelerated healing response seen with the bioactive coating is shown to be important to prevent migration of the particles within tissue. Additionally the PLGA coating did enhance the immune response early on in the in vivo studies corroborating with the in vitro findings.

The overall goal of this research was to engineer an injectable material that can be used to induce an acute immune response which will lead to the accelerated production of extracellular matrix proteins to augment tissue and eventually create a soft tissue network with the ultimate clinical application being dermal augmentation, periurethral bulking, or gingival augmentation.