IntroductionProgressive remodeling of the left ventricular (LV) architecture occurs after myocardial infarction (MI). While initially required for maintenance of cardiac output, this response ultimately leads to LV dysfunction and heart failure in the absence of a recurrent ischemic event [1,2]. Even with current optimal therapy, mortality in end-stage-heart-failure amounts to 20-50% per year [3]. Heart transplantation is applied as the last therapeutic option for patients with terminal heart-failure, but requests for organ transplantation far outstrip the number of donor organs. Therefore, new therapeutic strategies are urgently needed in order to ameliorate both patient prognosis and quality of life.Following MI, dilatation of the LV cavity has the effect of increasing LV wall tension, which triggers further dilatation of the LV cavity, and progression down a spiral of adverse cardiac remodeling towards the advanced stages of cardiac failure [4]. To restore wall tension, the endoventricular circular patch plasty technique (the Dor procedure) [5,6] and partial left ventriculectomy (the Batista procedure) [4] have been clinically implemented for severe cardiac dilation and dysfunction many years after an infarction. Employing a similar strategy to limit the remodeling pathway at an earlier stage, epicardial restraint therapies, such as the Acorn Cardiac Support Device [7], and the Paracor device [8] have been investigated. However, these both apply materials that are non-biodegradable and result in a permanent foreign body encapsulating the epicardium. Using biodegradable and elastic polyester urethane urea, we recently reported that cardiac patch implantation onto a chronic myocardial infarct prevented further cardiac dilatation and improved contraction, while altering LV wall thickness and compliance [9].Supported by a finite element model simulation [10], another concept in locally treating the failing cardiac wall was proposed where a bulking material is injected into the infarcted left ventricular wall to positively alter cardiac mechanics and result in a potentially beneficial NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript reduction of elevated stresses in the infarcted wall. In this numerical model the local systolic fiber stress distribution was determined in an infarcted LV wall injected with a mechanically passive material. The simulation showed that injection of a volume 4.5% that of the total LV wall volume and with a stiffness (elastic modulus) 20% of the natural LV tissue into the infarct border zone could decrease the fiber stress in the border zone of the infarct by 20% compared to a control simulation in which there was no injection. The mechanical simulation also showed that this attenuation effect on LV wall stress increased with the injection volume and the modulus of the injected material.Thermally responsive hydrogels are particularly attractive materials for injection therapy following MI since it is possible to inject the necessary fluid volumes from a syrin...

A biohybrid composite consisting of extracellular matrix (ECM) gel from porcine dermal tissue and biodegradable elastomeric fibers was generated and evaluated for soft tissue applications. ECM gel possesses attractive biocompatibility and bioactivity with weak mechanical properties and rapid degradation, while electrospun biodegradable poly(ester urethane)urea (PEUU) has good mechanical properties but limited cellular infiltration and tissue integration. A concurrent gel electrospray/polymer electrospinning method was employed to create ECM gel/PEUU fiber composites with attractive mechanical properties, including high flexibility and strength. Electron microscopy revealed a structure of interconnected fibrous layers embedded in ECM gel. Tensile mechanical properties could be tuned by altering the PEUU/ECM weight ratio. Scaffold tensile strengths for PEUU/ECM ratios of 67/33, 72/28 and 80/20 ranged from 80–187 kPa in the longitudinal axis (parallel to the collecting mandrel axis) and 41–91 kPa in the circumferential axis with 645–938% breaking strains. The 72/28 biohybrid composite and a control scaffold generated from electrospun PEUU alone were implanted into Lewis rats, replacing a full-thickness abdominal wall defect. At 4 wk, no infection or herniation was found at the implant site. Histological staining showed extensive cellular infiltration into the biohybrid scaffold with the newly developed tissue well integrated with the native periphery, while minimal cellular ingress into the electrospun PEUU scaffold was observed. Mechanical testing of explanted constructs showed evidence of substantial remodeling, with composite scaffolds adopting properties more comparable to the native abdominal wall. The described elastic biohybrid material imparts features of ECM gel bioactivity with PEUU strength and handling to provide a promising composite biomaterial for soft tissue repair and replacement.

Biodegradable elastomeric scaffolds are of increasing interest for applications in soft tissue repair and regeneration, particularly in mechanically active settings. The rate at which such a scaffold should degrade for optimal outcomes, however, is not generally known and the ability to select from similar scaffolds that vary in degradation behavior to allow such optimization is limited. Our objective was to synthesize a family of biodegradable polyurethane elastomers where partial substitution of polyester segments with polycarbonate segments in the polymer backbone would lead to slower degradation behavior. Specifically, we synthesized poly(ester carbonate)urethane ureas (PECUUs) using a blended soft segment of poly(caprolactone) (PCL) and poly(1,6-hexamethylene carbonate) (PHC), a 1,4-diisocyanatobutane hard segment and chain extension with putrescine. Soft segment PCL/PHC molar ratios of 100/0, 75/25, 50/50, 25/75, and 0/100 were investigated. Polymer tensile strengths varied from 14-34 MPa with breaking strains of 660-875%, initial moduli of 8-24 MPa and 100% recovery after 10% strain. Increased PHC content was associated with softer, more distensible films. Scaffolds produced by salt leaching supported smooth muscle cell adhesion and growth in vitro. PECUU in aqueous buffer in vitro and subcutaneous implants in rats of PECUU scaffolds showed degradation slower than comparable poly(ester urethane)urea and faster than poly(carbonate urethane)urea. These slower degrading thermoplastic polyurethanes provide opportunities to investigate the role of relative degradation rates for mechanically supportive scaffolds in a variety of soft tissue repair and reconstructive procedures.