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 @entity568 ( @entity568 ) siRNA and endothelial @entity842 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 @entity35 model. The doses of @entity568 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 Raman microspectroscopy revealed that in addition to changes in @entity32 and angiogenesis, there were also changes in the extracellular matrix (ECM) at seven days. While changes in sulfated glycosaminoglycan (sGAG) content of the ECM were not detected, changes in the binding of sGAG of the ECM to growth factors were observed. Two growth factors tested, @entity1655 and @entity664 showed increased binding to sGAG extracted from eNOS pDNA-treated samples at seven days, increasing the angiogenic potential of the ECM. Thus, we observe that changes in the tissue in terms of the balance of @entity32 and angiogenesis as well changes in the activity of sGAG of the ECM occurs following dual delivery of nucleic acids from the collagen sphere-in-hydrogel system.

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

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity664 :: ('54250(Tax:10116)', 'Gene') :: ['bFGF'] @entity568 :: ('24498(Tax:10116)', 'Gene') :: ['interleukin-6', 'IL-6'] @entity1655 :: ('MESH:C467484', 'Chemical') :: ['VEGF165'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity32 :: (MESH:D007249,Disease) :: ['inflammation']
