Xiaochu Ding

Hydrogen sulfide (H ₂ S) is an endogenous gasotransmitter that possesses multiple pathological and physiological functions, including anti‐inflammation, anti‐thrombosis, anti‐calcification, inhibition of intimal hyperplasia, and promotion of angiogenesis. Therefore, we aim to design an H ₂ S‐releasing resorbable synthetic graft that utilizes the therapeutic benefits of the H ₂ S to modulate the graft regeneration. To ease fabrication of the H ₂ S‐releasing graft, we have designed a pair of functional polyesters that are electrospinnable and photocurable to form an elastic fibrous conduit. The conduit bears free thiol groups that are conjugated with a methacrylated H ₂ S donor through thiol‐ene click chemistry to form an H ₂ S‐releasing graft. The graft can sustainably release H ₂ S over ∼12 days in vitro . Differing from prior designs, the H ₂ S‐releasing graft simultaneously possesses key features of a robust elasticity, and suitable mechanical properties, degradation rate and porosity. At the proof‐of‐concept stage, we examined the H ₂ S stimulation on endothelial cell growth using the graft with a low H ₂ S releasing rate. The results demonstrated that the graft with sustained H ₂ S release could significantly promote endothelial cell growth in vitro . This work paved the way for in vivo evaluation of the H ₂ S‐releasing graft.

Photocurable functional block copolyesters are reported to engineer elastomeric scaffolds for biomedical applications. The polymer backbone is organized by soft and stiff blocks. The functional prepolymer is readily crosslinked by thiol‐yne click chemistry under ulraviolet light in the presence of a photo‐initiator to form a robust elastomer. The elastomers bear both chemical crosslinks and crystal‐domain crosslinks to simultaneously tune the materials' properties, such as mechanical properties and degradation rates. The dual crosslinks can more efficiently tune the mechanical properties compared to the chemical crosslink alone. More importantly, the functional prepolymer is photo‐printable to construct elastomeric scaffolds with precise control of pore sizes using the state‐of‐the‐art digital light processing technique. With hydroxyls pendant on the backbone, human umbilical vein endothelial cells prefer to grow on the elastomer surface compared to that of a poly(caprolactone) film. It is believed that these functional photo‐polyesters will be useful to construct medical devices for bioengineering research.

A pair of alkyne- and thiol-functionalized polyesters are designed to engineer elastomeric scaffolds with a wide range of tunable material properties (e.g., thermal, degradation, and mechanical properties) for different tissues, given their different host responses, mechanics, and regenerative capacities. The two prepolymers are quickly photo-cross-linkable through thiol-yne click chemistry to form robust elastomers with small permanent deformations. The elastic moduli can be easily tuned between 0.96 +/- 0.18 and 7.5 +/- 2.0 MPa, and in vitro degradation is mediated from hours up to days by adjusting the prepolymer weight ratios. These elastomers bear free hydroxyl and thiol groups with a water contact angle of less than 85.6 +/- 3.58 degrees, indicating a hydrophilic nature. The elastomer is compatible with NIH/3T3 fibroblast cells with cell viability reaching 88 +/- 8.7% relative to the TCPS control at 48 h incubation. Differing from prior soft elastomers, a mixture of the two prepolymers without a carrying polymer is electrospinnable and UV-cross-linkable to fabricate elastic fibrous scaffolds for soft tissues. The designed prepolymer pair can thus ease the fabrication of elastic fibrous conduits, leading to potential use as a resorbable synthetic graft. The elastomers could find use in other tissue engineering applications as well.

An alkyne-functionalized elastomer derived from sebacic acid, 1,3propanediol, and alkyne-functionalized serinol is synthesized via melt condensation. A low-power UV lamp triggers the cross-linking rapidly via thiol-yne click chemistry. The cross-linking behavior is studied by photorheology and NMR spectroscopy. The resultant elastomer possesses mechanical properties similar to those of human soft tissues and exhibits in vitro degradability and good cytocompatibility.

Multiple additive manufacturing techniques have been developed in recent years to produce structures with tunable physical, chemical, and mechanical properties and defined architecture. Solution electrospinning, although an older and more established technique, normally cannot achieve the pattern resolution and tunability of these newer manufacturing techniques. In this study, we present solution electrowriting as a method to produce fibrous conduits from various polymers with tunable patterns, dimensions, and scaffold porosity. We demonstrate the importance of solvent selection during solution electrowriting and discuss how solvent polarity and volatility can be exploited to controllably alter the structure of the resulting scaffolds. The technique can be readily implemented with equipment for conventional electrospinning and offers versatility, control, and customization that is uncommon in the solution electrospinning field.

Poly(glycerol‐sebacate) (PGS) is a biodegradable elastomer known for its mechanical properties and biocompatibility for soft tissue engineering. However, harsh thermal crosslinking conditions are needed to make PGS devices. To facilitate the thermal crosslinking, citric acid is explored as a crosslinker to form poly(glycerol sebacate citrate) (PGSC) elastomers. The effects of varying citrate contents and curing times are investigated on the mechanical properties, elasticity, degradation, and hydrophilicity. To examine the potential presence of unreacted citric acid, material acidity is monitored in relation to the citrate content and curing times. It is discovered that a low citrate content and a short curing time produce PGSC with tunable mechanical characteristics similar to PGS with enhanced elasticity. The materials demonstrate good cytocompatibility with human umbilical vein endothelial cells similar to the PGS control. The research study suggests that PGSC is a potential candidate for large‐scale biomedical applications because of the quick thermal crosslink and tunable elastomeric properties.

Digital light processing (DLP)-based three-dimensional (3D) printing offers large improvements in fabrication throughput and spatial resolution when compared to various other additive manufacturing techniques. Both properties are highly desirable when fabricating biomaterial scaffolds that require design precision. Poly(glycerol sebacate) acrylate (PGSA) is a degradable, biocompatible, and photocurable elastomer. In this work, PGSA ink was developed for DLP 3D printing of porous tubular structures. Ink formulations with varying prepolymer concentrations (10–60 wt %), diluent (dimethyl sulfoxide (DMSO), 2-butoxyethyl acetate (EGBEA), and 1:1 DMSO/EGBEA), and degree of PGSA acrylation (17–75%) were studied to optimize printing efficiency and bulk properties of the printed scaffolds. Prepolymer inks with viscosity (<5 Pa·s) and photopolymerization kinetics (exposure time <10 s) appropriate for DLP were developed. Photocrosslinked PGSA scaffolds were further exposed to postfabrication treatments including additional UV exposure or thermal curing (150 °C) to demonstrate tunability in scaffold degradation kinetics and mechanical properties. Complementary to this effort, a 3D model-generation tool was developed to enable user-friendly customization of tubular scaffold design by controlling the pore and strut size of the volumetric mesh. The resulting DLP-printed PGSA scaffolds present high mimicry to complex 3D models with a minimum feature thickness of 80 μm. The tunable properties of PGSA coupled with enhanced precision in microstructure geometry provide a fabrication platform for a variety of tissue regeneration applications.

Strategies that can reduce harmful side effects of potent immunomodulatory drugs are in high demand to facilitate clinical translation of the newest generation of immunotherapy. Indeed, uncontrolled triggering of the immune system can lead to life-threatening cascade reactions such as e.g. cytokine storm. In particular, drug formulations that combine simplicity and degradability are of formidable relevance. Imidazoquinolines are an excellent example of such small molecule immunomodulatory drugs that exhibit in unformulated form a highly undesirable pharmacokinetic profile. Imidazoquinolines are potent inducers of type I interferons that are of great interest in the context of anti-cancer and anti-viral therapy through triggering of Toll like receptors 7 and 8. In this paper we aimed to alter the pharmacokinetic profile of imidazoquinolines using a simple, yet efficient, strategy that holds high potential for clinical translation. Hereto, we conjugated an imidazoquinoline to the backbone of poly(aspartate) and further formulated this into a degradable coacervate through complex coacervation with a non-toxic degradable polycation. The intrinsic TLR activity of the imidazoquinoline was well preserved and our formulation strategy offered spatial control over its biological activity in vivo.

Mechanical properties and degradation profile are important parameters for the applications of biodegradable polyester such as poly(glycerol sebacate) in biomedical engineering. Here, a strategy is reported to make palmitate functionalized poly(glycerol sebacate) (PPGS) to alter the polymer hydrophobicity, crystallinity, microstructures and thermal properties. The changes of these intrinsic properties impart tunable degradation profiles and mechanical properties to the resultant elastomers depending on the palmitate contents. When the palmitates reach up to 16 mol%, the elastic modulus is tuned from initially 838 ± 55 kPa for the PGS to 333 ± 21 kPa for the PPGS under the same crosslinking conditions. The elastomer undergoes reversible elastic deformations for at least 1000 cycles within 20% strain without failure and shows enhanced elasticity. The polymer degradation is simultaneously inhibited because of the increased hydrophobicity. This strategy is different with other PGS modifications which could form a softer elastomer with less crosslinks but typically lead to a quicker degradation. Because the materials are made from endogenous molecules, they possess good cytocompatibility similar to the PGS control. Although these materials are designed specifically for small arteries, it is expected that they will be useful for other soft tissues too.