Gene-modified-tissue engineering of bone: overexpression and inhibition of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs and RECK) by osteoblasts from human mesenchymal stem cells seeded on collagen-chitosan

Abstract

The urban concentration and greater longevity have provided the increased number of chronic diseases and injuries arising from violence, especially bone loss. The classical therapy is the use of autologous grafts, but alternatives such as allograft, alloplastic or xenogenous are part of the therapeutic arsenal of the clinician. However, it is know that all have advantages and disadvantages, resulting in the absence of an ideal material to repair these lesions. The tissue engineering aims to use the cells of patients, combined with appropriate scaffolds, and stimulate them with growth factors / differentiation and extracellular matrix molecules (ECM) to produce new tissue in vitro. Our group has been studying potential biomaterials and growth factors for bone bioengineering, as well as the role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs and RECK) in the development and bone repair and biomaterial-ECM interaction in vivo. This project intends to verify if changing gene expression, either by overexpression or inhibition (interference), of MMPs (-2, -9 and -14), capable of cleavage all components of ECM, as well as of their inhibitors, the TIMPs (-1, -2, -3 and -4) and RECK, can modulate osteogenesis in vitro and in vivo by modifying the rate of degradation of a synthetic substrate potentially applicable to the tissue bioengineering: the composite collagen-chitosan. Further investigation of other genes related to osteogenesis, ECM components and cell adhesion that may be differentially expressed in the presence of biomaterial, and interventions in gene expression will also be performed. (AU)