Modulation of inflammation and angiogenesis and changes in ECM GAG-activity via dual delivery of nucleic acids.

Modulation of inflammation and angiogenesis and changes in ECM GAG-activity via dual delivery of nucleic acids. Biomaterials. 2015 Aug 6;69:133-147 Authors: Browne S, Monaghan MG, Brauchle E, Berrio DC, Chantepie S, Papy-Garcia D, Schenke-Layland K, Pandit A Abstract Tissue-engineered organs and implants hold promise for the replacement of damaged and diseased organs. However, the foreign body response (FBR) is a major obstacle that compromises the function of tissue-engineered constructs, typically causing them to fail. Two components of FBR are an inflammatory response and a lack of vascularization. To overcome these limitations, a collagen system was developed to release interleukin-6 (IL-6) siRNA and endothelial nitric oxide synthase (eNOS) pDNA in a staggered manner. Hollow collagen microspheres were assembled into a collagen sphere-in-hydrogel system that displayed a staggered release profile in vitro. This system was assessed in vivo in a subcutaneous rat model. The doses of IL-6 siRNA and eNOS pDNA were first individually optimized for their ability to reduce the volume fraction of inflammatory cells (7 days) and increase the length density of blood vessels (14 days), respectively. The identified optimal doses were combined, and the ability of the system to decrease the volume fraction of inflammatory cells and increase the length density of blood vessels was confirmed at both 7 and 14 days. Analysis of the tissue using Ram...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research