Mechanically tunable, human mesenchymal stem cell viable poly(ethylene glycol)-oxime hydrogels with invariant precursor composition, concentration, and stoichiometry.

Hydrogels are used widely for exploratory tissue engineering studies. However, currently no hydrogel systems have been reported that exhibit a wide range of elastic modulus without changing precursor concentration, identity, or stoichiometry. Herein, ester and amide-based PEG-oxime hydrogels with tunable moduli (~5-30 kPa) were synthesized with identical precursor mass fraction, stoichiometry, and concentration by varying the pH and buffer concentration of the gelation solution, exploiting the kinetics of oxime bond formation. The observed modulus range can be attributed to increasing amounts of network defects in slower forming gels, as confirmed by equilibrium swelling and small angle neutron scattering (SANS) experiments. Finally, hMSC viability was confirmed in these materials in a 24 h assay. While only an initial demonstration of the potential utility, the controlled variation in defect density and modulus is an important step forward in isolating system variables for hypothesis-driven biological investigations.

Zwitterionic amino acid-based Poly(ester urea)s suppress adhesion formation in a rat intra-abdominal cecal abrasion model.

Hernia repair outcomes have improved with more robust material options for surgeons and optimized surgical techniques. However, ventral hernia repairs remain challenging with an inherent risk of post-surgical adhesions in the peritoneal space which can occur regardless of interventional material or its surgical placement. Herein, amino acid-based poly(ester urea)s (PEUs) with varied amount of an allyl ether side chains were modified post polymerization modification with the zwitterionic sulfnate group (3-((3-((3-mercaptopropanoyl)oxy)propyl) dimethylammonio)propane-1-sulfonate) to promote anti-adhesive properties. These alloc-PEUs were processed using roll-to-roll fabrication methods to afford films that were amenable to surface functionalization via a zwitterion-thiol. Functional group availability on the surface was confirmed via fluorescence microscopy, x-ray photoelectron spectroscopy (XPS), and quartz crystal microbalance (QCM) measurements. Zwitterionic treated PEUs exhibited reduced fibrinogen adsorption in vitro when compared to unfunctionalized control polymer. A rat intrabdominal cecal abrasion adhesion model was used to assess the extent and tenacity of adhesion formation in the presence of the PEUs. The 10% alloc-PEU zwitterion functionalized material was found to reduce the extent and tenacity of adhesions when compared to adhesion controls and the unfunctionalized PEU controls.

Amino acid-based Poly(ester urea) copolymer films for hernia-repair applications.

The use of degradable materials is required to address current performance and functionality shortcomings from biologically-derived tissues and non-resorbable synthetic materials used for hernia mesh repair applications. Herein a series of degradable l-valine-co-l-phenylalanine poly(ester urea) (PEU) copolymers were investigated for soft-tissue repair. Poly[(1-VAL-8)0.7-co-(1-PHE-6)0.3] showed the highest uniaxial mechanical properties (332.5 ±â€¯3.5 MPa). Additionally, l-valine-co-l-phenylalanine poly(ester urea)s were blade coated on small intestine submucosa extracellular matrix (SIS-ECM) and found to enhance the burst test mechanical properties of SIS-ECM in composite films (force at break between 102.6 ±â€¯6.5-151.4 ±â€¯11.3 N). Free standing films of l-valine-co-l-phenylalanine PEUs were found to have superior extension at break when compared to SIS-ECM (averages between 1.2 and 1.9 cm and 1.2 cm respectively). Fibroblast (L-929) spreading, proliferation, and improved attachment over control were observed without toxicity in vitro, while a reduced inflammatory response at both 7 and 14 days post-implant was observed for poly[(1-VAL-8)⁠0.7-co-(1-PHE-6)⁠0.3] when compared to polypropylene in an in vivo rat hernia model. These results support the use of PEU copolymers as free-standing films or as composite materials in soft-tissue applications for hernia-repair.

Post-fabrication QAC-functionalized thermoplastic polyurethane for contact-killing catheter applications.

The use of catheters is ubiquitous in medicine and the incidence of infection remains unacceptably high despite numerous advances in functional surfaces and drug elution. Herein we report the use of a thermoplastic polyurethane containing an allyl ether side-chain functionality (allyl-TPU) that allows for rapid and convenient surface modification with antimicrobial reagents, post-processing. This post-processing functionalization affords the ability to target appropriate TPU properties and maintain the functional groups on the surface of the device where they do not affect bulk properties. A series of quaternary ammonium thiol compounds (Qx-SH) possessing various hydrocarbon tail lengths (8-14 carbons) were synthesized and attached to the surface using thiol-ene "click" chemistry. A quantitative assessment of the amount of Qx-SH available on the surface was determined using fluorescence spectroscopy and X-ray photoelectron spectroscopy (XPS). Contact-killing assays note the Q8-SH composition has the highest antimicrobial activity, and a live/dead fluorescence assay reveals rapid contact-killing of Staphylococcus aureus (>75% in 5 min) and Escherichia coli (90% in 10 min) inocula. Scale-up and extrusion of allyl-TPU provides catheter prototypes for biofilm formation testing with Pseudomonas aeruginosa, and surface-functionalized catheters modified with Q8-SH demonstrate their ability to reduce biofilm formation.

Antimicrobial and Antifouling Strategies for Polymeric Medical Devices.

Hospital-acquired infections arising from implanted polymeric medical devices continue to pose a significant challenge for medical professionals and patients. Often times, these infections arise from biofilm accumulation on the device, which is difficult to eradicate and usually requires antibiotic treatment and device removal. In response, significant efforts have been made to design functional polymeric devices or coatings that possess antimicrobial or antifouling properties that limit biofilm formation and subsequent infection by inhibiting or eliminating bacteria near the device surface or by limiting the initial attachment of proteins and bacteria. In this Viewpoint, we highlight the magnitude of device-associated infections, the role of biofilm formation in human pathogenesis, and recent advances in antimicrobial and antifouling polymers, as well as current strategies employed in commercial devices for preventing infection.

Control of Mesh Size and Modulus by Kinetically Dependent Cross-Linking in Hydrogels.

Kinetically controlled cross-linking processes produce mechanically distinguishable hydrogels using identical precursor chemistry. The oxime ligation demonstrates tunable reaction kinetics with pH and buffer strength, which induce changes in the structural features of hydrogels and determine their mechanical properties. Small-angle neutron scattering and swelling studies provide an insight into how structural properties correlate with mechanical properties for this hydrogel system.