Delivery of an engineered HGF fragment in an extracellular matrix-derived hydrogel prevents negative LV remodeling post-myocardial infarction.

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.

Award winner for outstanding research in the PhD category, 2014 Society for Biomaterials annual meeting and exposition, Denver, Colorado, April 16-19, 2014: Decellularized adipose matrix hydrogels stimulate in vivo neovascularization and adipose formation.

Decellularization of tissues offers the ability to produce tissue-specific extracellular matrix (ECM) scaffolds that recreate many of the biochemical aspects of the tissue of interest. In this study, we describe the in vivo function of decellularized adipose ECM hydrogels for treating subcutaneous adipose deficits. Adipose ECM hydrogels were combined with either adipose-derived adult stem cells or a biocompatible cross-linker, injected subcutaneously into nude mice, and evaluated over the course of 1 month. These ECM hydrogels showed improved integration with the surrounding tissue in vivo compared to a clinical standard soft tissue filler, Juvederm, and stimulated neovascularization. More importantly, these adipose ECM hydrogels facilitated new adipose regeneration within the material at 1 month, a feature not seen with current clinical soft tissue fillers. These results contribute to the growing evidence that ECM-based materials are capable of stimulating subcutaneous adipose regeneration, suggesting that future soft tissue filler materials could incorporate ECM elements in order to restore function to adipose deficits instead of simply filling them with static materials.

Quantitative percussion diagnostics and bone density analysis of the implant-bone interface in a pre- and postmortem human subject.

PURPOSE: It has been hypothesized that a correlation exists between the density of surrounding cortical bone and the stability of an implant under percussion loading that can be used to quantify the implant's osseointegration. The purpose of the present research was to explore whether quantitative percussion testing of dental implants gives reasonable indications of the level of osseointegration that are consistent with bone configuration and its influence on osseointegration quality. MATERIALS AND METHODS: Data from percussion testing of a live human subject, obtained using the Periometer, were compared with corresponding bone density estimates from high-resolution computed tomography images and postmortem percussion probe data. RESULTS: The results confirm the hypothesis that the nature of an implant's response to percussion is determined by its cortical bone support. CONCLUSIONS: The findings suggest that the cortical bone supporting the crestal and apical regions of the implant is primarily responsible for structural stability.