Current bioinks for 3D bioprinting, such as gelatin-methacryloyl, are generally low viscosity fluids at room temperature, requiring specialized systems to create complex geometries.

Instability to storage and shipping conditions and injection administration remain major challenges in treating chronic conditions with biopharmaceuticals. Herein, formulations of poly(trehalose methacrylate) (pTrMA) were successfully optimized to stabilize insulin without appreciably increasing viscosity. Polymers were synthesized (2,400 - 29,200 Da), and added to insulin at different concentrations. pTrMA maintained >95% intact insulin against 250 rpm at 37 °C for 3 hours with at least 10 mol. eq. of 5.0 kDa, 7.5 mol. eq. of 9.4 kDa, 5 mol. eq. of 12.8 kDa, 1 mol. eq. of 19.8 kDa, and 0.5 mol. eq. of 29.2 kDa polymers, compared to 13.1% of insulin alone. The lowest pTrMA concentration formulations were more viscous than insulin alone, but the highest viscosity, U-600 with 10 mol. eq. of 5 kDa pTrMA, was only 1.43 cP at 25 °C. This data demonstrates that pTrMA is a promising low viscosity additive to stabilize the diabetes therapeutic insulin.

In order to better understand the relationship between Flagelliform (Flag) spider silk molecular structural organization and the mechanisms of fiber assembly, it was designed and produced the Flag spidroin analogue rNcFlag2222. The recombinant proteins are composed by the elastic repetitive glycine-rich motifs (GPGGX/GGX) and the spacer region, rich in hydrophilic charged amino acids, present at the native silk spidroin. Using different approaches for nanomolecular protein analysis, the structural data of rNcFlag2222 recombinant proteins were compared in its fibrillar and in its fully solvated states. Based on the results was possible to identify the molecular structural dynamics of NcFlag2222 prior to and after fiber formation. Overal rNcFlag2222 shows a mixture of semiflexible and rigid conformations, characterized mostly by the presence of PPII, β-turn and β-sheet. These results agree with previous studies and bring insights about the molecular mechanisms that might driven Flag silk fibers assembly and elastomeric behavior.

Islet transplantation within mechanically stable microcapsules offers the promise of long-term diabetes reversal without chronic immunosuppression. Reinforcing the ionically gelled network of alginate (ALG) hydrogels with covalently linked polyethylene glycol (PEG) may create hybrid structures with desirable mechanical properties. This report describes the fabrication of hybrid PEG-ALG interpenetrating polymer networks and the investigation of microcapsule swelling, surface modulus, rheology, compression, and permeability. It is demonstrated that hybrid networks are more resistant to bulk swelling and compressive deformation and display improved shape recovery and long-term resilience. Interestingly, it is shown that PEG-ALG networks behave like ALG during microscale surface deformation and small amplitude shear while exhibiting similar permeability properties. The results from this report's in vitro characterization are interpreted according to viscoelastic polymer theory and provide new insight into hybrid hydrogel mechanical behavior. This new understanding of PEG-ALG mechanical performance is then linked to previous work that demonstrated the success of hybrid polymer immunoisolation devices in vivo.

Failure of dental composite restorations is primarily due to recurrent decay at the tooth-composite interface. At this interface, the adhesive and its bond with dentin is the barrier between the restored tooth and the oral environment. In vivo degradation of the bond formed at the adhesive/dentin (a/d) interface follows a cascade of events leading to weakening of the composite restoration. Here, a peptide-based approach is developed to mineralize deficient dentin matrices at the a/d interface. Peptides that have an inherent capacity to self-assemble on dentin and to induce calcium-phosphate remineralization are anchored at the interface. Distribution of adhesive, collagen, and mineral is analyzed using micro-Raman spectroscopy and fluorescence microscopy. The analysis demonstrates remineralization of the deficient dentin matrices achieved throughout the interface with homogeneous distribution of mineral. The peptide-based remineralization demonstrated here can be an enabling technology to design integrated biomaterial-tissue interfaces.

The processes used to create synthetic spider silk greatly affect the properties of the produced fibers. This paper investigates the effect of process variations during artificial spinning on the thermal and mechanical properties of the produced silk. Property values are also compared to the ones of the natural dragline silk of the spider, and to unprocessed (as-spun) synthetic silk. Structural characterization by scanning pyroelectric microscopy is employed to provide insight into the axial orientation of the crystalline regions of the fiber and is supported by XRD data. The results show that stretching and passage through liquid baths induce crystal formation and axial alignment in synthetic fibers, but with different structural organization than natural silks. Furthermore, an increase in thermal diffusivity and elastic modulus is observed with decreasing fiber diameter, trending towards properties of natural fiber. This effect seems to be related to silk fibers being subjected to a radial gradient during production.

The polyacrylonitrile/polymethyl-methacrylate (PMMA/PAN) porous fibers, core-shell hollow fibers, and porous thin films are prepared by coaxial electrospinning, single electrospinning, and spin-coating technologies, respectively. The different morphologies arising from different processes display great influences on their thermal and crystalline properties. The adding of PMMA causes porous structure due to the microphase-separation structure of immiscible PMMA and PAN phases. The lower weight loss, higher degradation temperature, and glass-transition temperatures of porous thin films than those of porous fibers and core-shell hollow fibers are obtained, evidencing that the polymer morphologies produced from the different process can efficiently influence their physical properties. The orthorhombic structure of PAN crystals are found in the PMMA/PAN porous thin films, but the rotational disorder PAN crystals due to intermolecular packing are observed in the PMMA/PAN porous fibers and core-shell hollow fibers, indicating that different processes cause different types of PAN crystals.

The effects of ethylene oxide (EO), vaporized hydrogen peroxide (VHP), gamma (γ) radiation, and electron-beam (E-beam) on the physiochemical and morphological properties of medical device polymers are investigated. Polymers with ether, carbonate, carboxylic acid, amide and ester functionalities are selected from a family of poly(ethylene glycol) (PEG) containing tyrosine-derived polycarbonates (TyrPCs) to include slow, medium, fast, and ultrafast degrading polymers. Poly(lactic acid) (PLA) is used for comparison. Molecular weight () of all tested polymers decreases upon gamma and E-beam, and this effect becomes more pronounced at higher PEG content. Gamma sterilization increases the glass transition temperature of polymers with high PEG content. EO esterifies the carboxylic acid groups in desaminotyrosol-tyrosine (DT) and causes significant degradation. VHP causes hydroxylation of the phenyl ring, and hydrolytic degradation. This study signifies the importance of the chemical composition when selecting a sterilization method, and provides suggested conditions for each of the sterilization methods.

Flexible polymers such as poly dimethyl siloxane (PDMS) can be patterned at the micro- and nanoscale by casting, for a variety of applications. This replication-based fabrication process is relatively cheap and fast, yet injection molding offers an even faster and cheaper alternative to PDMS casting, provided thermoplastic polymers with similar mechanical properties can be used. In this paper, a thermoplastic polyurethane is evaluated for its patterning ability with an aim to forming the type of flexible structures used to measure and modulate the contractile forces of cells in tissue engineering experiments. The successful replication of grating structures is demonstrated with feature sizes as low as 100 nm and an analysis of certain processing conditions that facilitate and enhance the accuracy of this replication is presented. The results are benchmarked against an optical storage media grade polycarbonate.

A self-cleaning membrane that periodically rids itself of attached cells to maintain glucose diffusion could extend the lifetime of implanted glucose biosensors. Herein, we evaluate the functionality of thermoresponsive double network (DN) hydrogel membranes based on poly(-isopropylacrylamide) (PNIPAAm) and an electrostatic co-monomer, 2-acrylamido-2-methylpropane sulfonic acid (AMPS). DN hydrogels are comprised of a tightly crosslinked, ionized first network [P(NIPAAm-co-AMPS)] containing variable levels of AMPS (100:0-25:75 wt% ratio of NIPAAm:AMPS) and a loosely crosslinked, interpenetrating second network [PNIPAAm]. To meet the specific requirements of a subcutaneously implanted glucose biosensor, the volume phase transition temperature is tuned and essential properties, such as glucose diffusion kinetics, thermosensitivity, and cytocompatibility are evaluated. In addition, the self-cleaning functionality is demonstrated through thermally driven cell detachment from the membranes in vitro.

1Biocompatible cellulose-based aerogels composed of nanoporous struts, which embed interconnected voids of controlled micron-size, have been prepared employing temporary templates of fused porogens, reinforcement by interpenetrating PMMA networks and supercritical carbon dioxide drying. Different combinations of cellulose solvent (Ca(SCN)/HO/LiCl or [EMIm][OAc]/DMSO) and anti-solvent (EtOH), porogen type (paraffin wax or PMMA spheres) and porogen size (various fractions in the range of 100-500 μm) as well as intensity of PMMA reinforcement have been investigated to tailor the materials for cell scaffolding applications. All aerogels exhibited an open and dual porosity (micronporosity >100 μm and nanoporosity extending to the low micrometer range). Mechanical properties of the dual-porous aerogels under compressive stress were considerably improved by introduction of interpenetrating PMMA networks. The effect of the reinforcing polymer on attachment, spreading, and proliferation of NIH 3T3 fibroblast cells, cultivated on selected dual-porous aerogels to pre-evaluate their biocompatibility was similarly positive.

1A microwave (MW)-assisted crosslinking process to prepare hydrogel-forming microneedle (MN) arrays was evaluated. Conventionally, such MN arrays are prepared using processes that includes a thermal crosslinking step. Polymeric MN arrays were prepared using poly(methyl vinyl ether-alt-maleic acid) crosslinked by reaction with poly(ethylene glycol) over 24 h at 80 °C. Polymeric MN arrays were prepared to compare conventional process with the novel MW-assisted crosslinking method. Infrared spectroscopy was used to evaluate the crosslinking degree, evaluating the area of the carbonyl peaks (2000-1500 cm). It was shown that, by using the MW-assisted process, MN with a similar crosslinking degree to those prepared conventionally can be obtained in only 45 min. The effects of the crosslinking process on the properties of these materials were also evaluated. For this purpose swelling kinetics, mechanical characterisation, and insertion studies were performed. The results suggest that MN arrays prepared using the MW assisted process had equivalent properties to those prepared conventionally but can be produced 30 times faster. Finally, an caffeine permeation across excised porcine skin was performed using conventional and MW-prepared MN arrays. The release profiles obtained can be considered equivalent, delivering in both cases 3000-3500 μg of caffeine after 24 h.

We present a novel tensile testing system optimized for the mechanical loading of microliter volume protein hydrogels. Our apparatus incorporates a voice coil servoactuator capable of carrying out fixed velocity extension-relaxation cycles as well as extension step protocols. The setup is equipped with an acrylic cuvette permitting day-long incubations in solution. To demonstrate the functionality of the device, we photochemically crosslinked polyproteins of the I91 immunoglobulin domain from the muscle protein titin to create solid hydrogels that recapitulate elastic properties of muscle. We present data from tensile tests of these low volume biomaterials that support protein unfolding as a main determinant of the elasticity of protein hydrogels. Our results demonstrate the potential use of protein hydrogels as biomaterials whose elastic properties dynamically respond to their environment.

Current synthetic vascular grafts have poor patency rates in small diameter applications (<6 mm) due to intimal hyperplasia arising from a compliance mismatch between the graft and native vasculature. Enormous efforts have focused on improving biomechanical properties; however, polymeric grafts are often constrained by an inverse relationship between burst pressure and compliance. We have developed a new, semi-interpenetrating network (semi-IPN) approach to improve compliance without sacrificing burst pressure. The effects of heat treatment on graft morphology, fiber architecture, and resultant biomechanical properties are presented. In addition, biomechanical properties after equilibration at physiological temperature were investigated in relation to polyurethane microstructure to better predict performance. Compliance values as high as 9.2 ± 2.7 %/mmHg x 10 were observed for the semi-IPN graft while also maintaining high burst pressure, 1780 ± 230 mm Hg. The high compliance of these heat-treated poly(carbonate urethane) (PCU) and semi-IPN grafts is expected to improve long-term patency rates beyond even saphenous vein autografts by preventing intimal hyperplasia. The fundamental structure-property relationships gained from this work may also be utilized to advance biomedical device designs based on thermoplastic polyurethanes.

The properties of synthetic hydrogels can be tuned to address the needs of many tissue-culture applications. This work characterizes the swelling and mechanical properties of thiol-ene crosslinked PEG hydrogels made with varying prepolymer formulations, demonstrating that hydrogels with a compressive modulus exceeding 600 kPa can be formed. The amount of peptide incorporated into the hydrogel is shown to be proportional to the amount of peptide in the prepolymer solution. Cell attachment and spreading on the surface of the peptide-functionalized hydrogels is demonstrated. Additionally, a method for bonding distinct layers of cured hydrogels is used to create a microfluidic channel.

Planar electronics processing methods have enabled neural interfaces to become more precise and deliver more information. However, this processing paradigm is inherently 2D and rigid. The resulting mechanical and geometrical mismatch at the biotic-abiotic interface can elicit an immune response that prevents effective stimulation. In this work, a thiol-ene/acrylate shape memory polymer is utilized to create 3D softening substrates for stimulation electrodes. This substrate system is shown to soften from more than 600 to 6 MPa. A nerve cuff electrode that coils around the vagus nerve in a rat and that drives neural activity is demonstrated.

We have recently reported upon the development of crosslinked urethane-doped polyester (CUPE) network elastomers, which was motivated by the desire to overcome the drawbacks presented by crosslinked network polyesters and biodegradable polyurethanes for soft tissue engineering applications. Although the effect of the isocyanate content and post-polymerization conditions on the material structure-property relationship was examined in detail, the ability of the diol component to modulate the material properties was only studied briefly. Herein, we present a detailed report on the development of CUPE polymers synthesized using diols 4, 6, 8, 10, or 12 methylene units in length in order to investigate what role the diol component plays on the resulting material's physical properties, and assess their long-term biological performance in vivo. An increase in the diol length was shown to affect the physical properties of the CUPE polymers primarily through lowered polymeric crosslinking densities and elevated material hydrophobicity. The use of longer chain diols resulted in CUPE polymers with increased molecular weights resulting in higher tensile strength and elasticity, while also increasing the material hydrophobicity to lower bulk swelling and prolong the polymer degradation rates. Although the number of methylene units largely affected the physical properties of CUPE, the choice of diol did not affect the overall polymer cell/tissue-compatibility both in vitro and in vivo. In conclusion, we have established the diol component as an important parameter in controlling the structure-property relationship of the polymer in addition to diisocyanate concentration and post-polymerization conditions. Expanding the family of CUPE polymers increases the choices of biodegradable elastomers for tissue engineering applications.