4D polycarbonates via stereolithography as scaffolds for soft tissue repair

3D printing has emerged as one of the most promising tools to overcome the processing and morphological limitations of traditional tissue engineering scaffold design. However, there is a need for improved minimally invasive, void-filling materials to provide mechanical support, biocompatibility, and surface erosion characteristics to ensure consistent tissue support during the healing process. Herein, soft, elastomeric aliphatic polycarbonate-based materials were designed to undergo photopolymerization into supportive soft tissue engineering scaffolds. The 4D nature of the printed scaffolds is manifested in their shape memory properties, which allows them to fill model soft tissue voids without deforming the surrounding material. In vivo, adipocyte lobules were found to infiltrate the surface-eroding scaffold within 2 months, and neovascularization was observed over the same time. Notably, reduced collagen capsule thickness indicates that these scaffolds are highly promising for adipose tissue engineering and repair

Elastomeric polyamide biomaterials with stereochemically tuneable mechanical properties and shape memory

Abstract: Biocompatible polymers are widely used in tissue engineering and biomedical device applications. However, few biomaterials are suitable for use as long-term implants and these examples usually possess limited property scope, can be difficult to process, and are non-responsive to external stimuli. Here, we report a class of easily processable polyamides with stereocontrolled mechanical properties and high-fidelity shape memory behaviour. We synthesise these materials using the efficient nucleophilic thiol-yne reaction between a dipropiolamide and dithiol to yield an α,β − unsaturated carbonyl moiety along the polymer backbone. By rationally exploiting reaction conditions, the alkene stereochemistry is modulated between 35–82% cis content and the stereochemistry dictates the bulk material properties such as tensile strength, modulus, and glass transition. Further access to materials possessing a broader range of thermal and mechanical properties is accomplished by polymerising a variety of commercially available dithiols with the dipropiolamide monomer

Bird-Like Anatomy, Posture, and Behavior Revealed by an Early Jurassic Theropod Dinosaur Resting Trace

BACKGROUND: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. CONCLUSIONS/SIGNIFICANCE: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods

Ring-Opening Copolymerization of Four-Dimensional Printable Polyesters Using Supramolecular Thiourea/Organocatalysis

Ring-opening copolymerization (ROCOP) of polyesters may be used to achieve a wide variety of functional polymers using commercial monomer libraries, but primarily make use of metallic catalysts such as tin, magnesium, or cobalt complexes. However, the limitations of such catalysts include toxicity risks and environmental concerns for both the desired application, such as biomaterials, and the end-of-life consideration. There is a need for cleaner, friendlier, and less expensive routes to polymeric materials and devices. Therefore, organobase-catalyzed ROCOP is an intriguing opportunity to improve both the safety and the structural control of the resultant polyesters. Here, organobases with and without supramolecular thiourea co-catalysts are demonstrated for ROCOP of functional polyesters made of cis-4-cyclohexene-1,2-dicarboxylic anhydride and allyl glycidol ether, with ROCOP performed in bulk, open-air conditions. The catalysts resulted in molecular weights of >25 kDa while maintaining controlled polymerization behaviors and a dispersity of <1.3. The role of the thiourea co-catalysts is further explored, with a proposed mechanism for initiation of the ROCOP system. The resultant polyesters are utilized in vat polymerization four-dimensional (4D) printing using thiol-ene cross-linking to manufacture complex prototypes that display shape memory. The role of molecular weight on physical properties, including mechanical and thermal behaviors, is explored along with hydrolytic degradation rates, shape memory responsiveness, and cytocompatibility. Ultimately, the use of organobase catalysis for ROCOP of polyester photopolymer is shown to be an efficient, tunable method of controlling resultant physical properties for improving the environmental friendliness, as well as biomaterial potential

Harnessing the chemical diversity of the natural product magnolol for the synthesis of renewable, degradable neolignan thermosets with tunable thermomechanical characteristics and antioxidant activity

Magnolol, a neolignan natural product with antioxidant properties, contains inherent, orthogonal, phenolic, and alkenyl reactive groups that were used in both direct thermoset synthesis, as well as the stepwise synthesis of a small library of monomers, followed by transformation into thermoset materials. Each monomer from the small library was prepared via a single step functionalization reaction of the phenolic groups of magnolol. Thermoset materials were realized through solvent-free, thiol–ene reactions, and the resulting cross-linked materials were each comprised of thioether and ester linkages, with one retaining the hydrophilic phenols from magnolol, another having the phenols protected as an acetonide, and two others incorporating the phenols into additional cross-linking sites via hydrolytically labile carbonates or stable ether linkages. With this diversity of chemical compositions and structures, the thermosets displayed a range of thermomechanical properties including glass transition temperatures, Tg, 29–52 °C, onset of thermal degradation, Td, from about 290–360 °C, and ultimate strength up to 50 MPa. These tunable materials were studied in their degradation and biological properties with the aim of exploiting the antioxidant properties of the natural product. Hydrolytic degradation occurred under basic conditions (pH = 11) in all thermosets, but with kinetics that were dependent upon their chemical structures and mechanical properties: 20% mass loss was observed at 5, 7, 27, and 40 weeks for the thermosets produced from magnolol directly, acetonide-protected magnolol, bis­(allyl carbonate)-functionalized magnolol, and bis­(allyl ether)-functionalized magnolol, respectively. Isolated degradation products and model compounds displayed antioxidant properties similar to magnolol, as determined by both UV–vis and in vitro reactive oxygen species (ROS) assays. As these magnolol-based thermosets were found to also allow for extended cell culture, these materials may serve as promising degradable biomaterials

Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast

Septin hetero-oligomers polymerize into cytoskeletal filaments with essential functions in many eukaryotic cell types. Mutations within the oligomerization interface that encompasses the GTP-binding pocket of a septin (its “G interface”) cause thermoinstability of yeast septin hetero-oligomer assembly, and human disease. When coexpressed with its wild-type counterpart, a G interface mutant is excluded from septin filaments, even at moderate temperatures. We show that this quality control mechanism is specific to G interface mutants, operates during de novo septin hetero-oligomer assembly, and requires specific cytosolic chaperones. Chaperone overexpression lowers the temperature permissive for proliferation of cells expressing a G interface mutant as the sole source of a given septin. Mutations that perturb the septin G interface retard release from these chaperones, imposing a kinetic delay on the availability of nascent septin molecules for higher-order assembly. Un­expectedly, the disaggregase Hsp104 contributes to this delay in a manner that does not require its “unfoldase” activity, indicating a latent “holdase” activity toward mutant septins. These findings provide new roles for chaperone-mediated kinetic partitioning of non-native proteins and may help explain the etiology of septin-linked human diseases