PleurAlert: an augmented chest drainage system with electronic sensing, automated alerts and internet connectivity.

We have enhanced a common medical device, the chest tube drainage container, with electronic sensing of fluid volume, automated detection of critical alarm conditions and the ability to automatically send alert text messages to a nurse's cell phone. The PleurAlert system provides a simple touch-screen interface and can graphically display chest tube output over time. Our design augments a device whose basic function dates back 50 years by adding technology to automate and optimize a monitoring process that can be time consuming and inconvenient for nurses. The system may also enhance detection of emergency conditions and speed response time.

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. In vitro bovine serum albumin (BSA) release was studied from hydrogels, poly(lactide-co-glycolide) microparticles, or microparticles mixed into the hydrogels. The synthesized copolymers were able to gel below 37°C and release protein in excess of 3 months. The presence of MANHS and AAc in the copolymers was associated with higher loaded protein retention during thermal transition (45% vs. 22%) and faster release (2 months), respectively. Microspheres entrapped in the hydrogel released protein in a delayed fashion relative to microspheres in saline. The combination of a protein-reactive hydrogel mixed with protein-loaded microspheres demonstrated a sequential release of specific BSA populations. Overall the described drug delivery system combines the advantages of injectability, degradability, extended release, and sequential release, which may be useful in tissue engineering applications.

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. Mechanical properties of the PUUs were characterized by tensile testing with static or cyclic loading and dynamic mechanical analysis. All of the PUUs synthesized showed large elongations at break (800-1400%) and high tensile strength (30-60 MPa). PUUs with noncrystalline SSs all showed improved elasticity and resilience relative to the crystalline PCL-based PUU, especially for the PUUs with high molecular weight SSs (PTMC 5400 M(n) and PVLCL 6000 M(n)), of which the permanent deformation after tensile failure was only 12 ± 7 and 39 ± 4%, respectively. The SS molecular weight also influenced the tensile modulus in an inverse fashion. Accelerated degradation studies in PBS containing 100 U/mL lipase showed significantly greater mass loss for the two polyester-based PUUs versus the polycarbonate-based PUU and for PVLCL versus PCL polyester PUUs. Basic cytocompatibility was demonstrated with primary vascular smooth muscle cell culture. The synthesized families of PUUs showed variable elastomeric behavior that could be explained in terms of the underlying molecular design and crystalline behavior. Depending on the application target of interest, these materials may provide options or guidance for soft tissue scaffold development.

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. The synthetic inducer ligand was first loaded into PEUU to demonstrate extended release of the bioactive molecule at various loading densities over a one year period in vitro. Patterning films of PEUU variably-loaded with inducer resulted in spatially controlled cell expression of the gene product (green fluorescent protein, GFP). In porous scaffolds made from PEUU by salt leaching, where the central region was exclusively loaded with inducer, cells expressed GFP predominately in the loaded central regions whereas expression was minimal in outer regions where ligand was omitted. This scaffold system may ultimately provide a means to precisely control progenitor cell commitment in a spatially-defined manner in vivo for soft tissue repair and regeneration.