RESUMO
Skeletal muscle tissue has an inherent capacity for regeneration following injury. However, severe trauma, such as volumetric muscle loss, overwhelms these natural muscle repair mechanisms prompting the search for a tissue engineering/regenerative medicine approach to promote functional skeletal muscle restoration. A desirable approach involves a bioscaffold that simultaneously acts as an inductive microenvironment and as a cell/drug delivery vehicle to encourage muscle ingrowth. Both biologically active, naturally derived materials (such as extracellular matrix) and carefully engineered synthetic polymers have been developed to provide such a muscle regenerative environment. Next generation naturally derived/synthetic "hybrid materials" would combine the advantageous properties of these materials to create an optimal platform for cell/drug delivery and possess inherent bioactive properties. Advances in scaffolds using muscle tissue engineering are reviewed herein.
Assuntos
Materiais Biocompatíveis/administração & dosagem , Músculo Esquelético/fisiologia , Polímeros/administração & dosagem , Regeneração/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais , HumanosRESUMO
A method for targeting to and retaining intravenously injected nanoparticles at the site of acute myocardial infarction in a rat model is described. Enzyme-responsive peptide-polymer amphiphiles are assembled as spherical micellar nanoparticles, and undergo a morphological transition from spherical-shaped, discrete materials to network-like assemblies when acted upon by matrix metalloproteinases (MMP-2 and MMP-9), which are up-regulated in heart tissue post-myocardial infarction.
Assuntos
Portadores de Fármacos/química , Coração/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Nanopartículas/química , Animais , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos/métodos , Difusão Dinâmica da Luz , Fluorescência , Interações Hidrofóbicas e Hidrofílicas , Injeções Intravenosas , Micelas , Infarto do Miocárdio/enzimologia , Miocárdio/enzimologia , Polímeros/química , Ratos , Fatores de TempoRESUMO
Hepatocyte growth factor (HGF) has been shown to have anti-fibrotic, pro-angiogenic, and cardioprotective effects; however, it is highly unstable and expensive to manufacture, hindering its clinical translation. Recently, a HGF fragment (HGF-f), an alternative c-MET agonist, was engineered to possess increased stability and recombinant expression yields. In this study, we assessed the potential of HGF-f, delivered in an extracellular matrix (ECM)-derived hydrogel, as a potential treatment for myocardial infarction (MI). HGF-f protected cardiomyocytes from serum-starvation and induced down-regulation of fibrotic markers in whole cardiac cell isolate compared to the untreated control. The ECM hydrogel prolonged release of HGF-f compared to collagen gels, and in vivo delivery of HGF-f from ECM hydrogels mitigated negative left ventricular (LV) remodeling, improved fractional area change (FAC), and increased arteriole density in a rat myocardial infarction model. These results indicate that HGF-f may be a viable alternative to using recombinant HGF, and that an ECM hydrogel can be employed to increase growth factor retention and efficacy.