Intramyocardial injection of a synthetic hydrogel with delivery of bFGF and IGF1 in a rat model of ischemic cardiomyopathy.

It is increasingly appreciated that the properties of a biomaterial used in intramyocardial injection therapy influence the outcomes of infarcted hearts that are treated. In this report the extended in vivo efficacy of a thermally responsive material that can deliver dual growth factors while providing a slow degradation time and high mechanical stiffness is examined. Copolymers consisting of N-isopropylacrylamide, 2-hydroxyethyl methacrylate, and degradable methacrylate polylactide were synthesized.

Extended and sequential delivery of protein from injectable thermoresponsive hydrogels.

Thermoresponsive hydrogels are attractive for their injectability and retention in tissue sites where they may serve as a mechanical support and as a scaffold to guide tissue remodeling. Our objective in this report was to develop a thermoresponsive, biodegradable hydrogel system that would be capable of protein release from two distinct reservoirs--one where protein was attached to the hydrogel backbone, and one where protein was loaded into biodegradable microparticles mixed into the network. Thermoresponsive hydrogels consisting of N-isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacrylate (HEMA), and biodegradable methacrylate polylactide were synthesized along with modified copolymers incorporating 1 mol % protein-reactive methacryloxy N-hydroxysuccinimide (MANHS), hydrophilic acrylic acid (AAc), or both.

Biodegradable polyurethane ureas with variable polyester or polycarbonate soft segments: effects of crystallinity, molecular weight, and composition on mechanical properties.

Biodegradable polyurethane urea (PUU) elastomers are ideal candidates for fabricating tissue engineering scaffolds with mechanical properties akin to strong and resilient soft tissues. PUU with a crystalline poly(ε-caprolactone) (PCL) macrodiol soft segment (SS) showed good elasticity and resilience at small strains (<50%) but showed poor resilience under large strains because of stress-induced crystallization of the PCL segments, with a permanent set of 677 ± 30% after tensile failure. To obtain softer and more resilient PUUs, we used noncrystalline poly(trimethylene carbonate) (PTMC) or poly(δ-valerolactone-co-ε-caprolactone) (PVLCL) macrodiols of different molecular weights as SSs that were reacted with 1,4-diisocyanatobutane and chain extended with 1,4-diaminobutane.

Controlled release of IGF-1 and HGF from a biodegradable polyurethane scaffold.

Purpose: Biodegradable elastomers, which can possess favorable mechanical properties and degradation rates for soft tissue engineering applications, are more recently being explored as depots for biomolecule delivery. The objective of this study was to synthesize and process biodegradable, elastomeric poly(ester urethane)urea (PEUU) scaffolds and to characterize their ability to incorporate and release bioactive insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF).

Methods: Porous PEUU scaffolds made from either 5 or 8 wt% PEUU were prepared with direct growth-factor incorporation.

Spatial control of gene expression within a scaffold by localized inducer release.

Gene expression can be controlled in genetically modified cells by employing an inducer/promoter system where presence of the inducer molecule regulates the timing and level of gene expression. By applying the principles of controlled release, it should be possible to control gene expression on a biomaterial surface by the presence or absence of inducer release from the underlying material matrix, thus avoiding alternative techniques that rely upon uptake of relatively labile DNA from material surfaces. To evaluate this concept, a modified ecdysone-responsive gene expression system was transfected into B16 murine cells and the ability of an inducer ligand, which was released from elastomeric poly(ester urethane) urea (PEUU), to initiate gene expression was studied.

Intra-myocardial biomaterial injection therapy in the treatment of heart failure: Materials, outcomes and challenges.

Heart failure initiated by coronary artery disease and myocardial infarction (MI) is a widespread, debilitating condition for which there are a limited number of options to prevent disease progression. Intra-myocardial biomaterial injection following MI theoretically provides a means to reduce the stresses experienced by the infarcted ventricular wall, which may alter the pathological remodeling process in a positive manner. Furthermore, biomaterial injection provides an opportunity to concurrently introduce cellular components and depots of bioactive agents.

Thermally responsive injectable hydrogel incorporating methacrylate-polylactide for hydrolytic lability.

Injectable thermoresponsive hydrogels are of interest for a variety of biomedical applications, including regional tissue mechanical support as well as drug and cell delivery. Within this class of materials there is a need to provide options for gels with stronger mechanical properties as well as variable degradation profiles. To address this need, the hydrolytically labile monomer, methacrylate-polylactide (MAPLA), with an average 2.

Synthesis, characterization and therapeutic efficacy of a biodegradable, thermoresponsive hydrogel designed for application in chronic infarcted myocardium.

Injection of a bulking material into the ventricular wall has been proposed as a therapy to prevent progressive adverse remodeling due to high wall stresses that develop after myocardial infarction. Our objective was to design, synthesize and characterize a biodegradable, thermoresponsive hydrogel for this application based on copolymerization of N-isopropylacrylamide (NIPAAm), acrylic acid (AAc) and hydroxyethyl methacrylate-poly(trimethylene carbonate) (HEMAPTMC). By evaluating a range of monomer ratios, poly(NIPAAm-co-AAc-co-HEMAPTMC) at a feed ratio of 86/4/10 was shown to be ideal since it formed a hydrogel at 37 degrees C, and gradually became soluble over a 5 month period in vitro through hydrolytic cleavage of the PTMC residues.

Outcome of noncardiac surgery in patients with ventricular assist devices.

An increasing number of patients are living with ventricular assist devices (VADs). Many of these patients will require noncardiac surgery for conditions not directly related to their VADs. The aim of this study was to assess the risks and outcomes of noncardiac surgery in these patients.