Carbonate Urethane Research Articles

Zwitterionic modification: A strategy to enhance the mechanical properties, lubricity and hemo- and biocompatibility of silicone poly(carbonate urethane urea)

Incorporating zwitterions into the blood-contacting materials has been demon-strated an effective and convenient strategy to minimize protein adsorption and platelet deposition, but is frequently detrimental to the mechanical properties. Herein a feeding 29.0 mol% sulfobetaine (SB) siloxane poly(carbonate urethane urea) (SSiPCUU) was synthesized and evaluated. Although the equilibrium water uptake ratio was increased to 1.20% markedly depressing the hydrolytic degradation resistance and mechanical properties after the zwitterionic modification, its maximum tensile stress and tear strength in the wet state still kept the highest among all the tested samples because the urea groups created therefrom gave rise to the formation of bifurcating hydrogen bonds making a significant contribution to the mechanical properties alongside the unique ion clusters formed from pendant SB species. As a consequence of zwitterionic incorporation, it exhibited an extremely low friction coefficient indicating an excellent lubricity in a wet environment without any post-treatment. Accordingly, both the nonspecific protein adsorption and platelet adhesion were evidently decreased. Moreover, it also depicted a good transparency. The high lubrication performance is desirable for lessening the damage to human blood vessels and a good transparency is favorable to the visualization of the flow of liquid in the catheter. These results illustrated the great potential of the zwitterionic SSiPCUU used in the preparation of balloon catheters, artificial blood vessels, stent coverings and other blood-contacting medical implants and devices.

Terpolymerizations of cyclohexene oxide, CO2, and isocyanates or isothiocyanates for the synthesis of poly(carbonate–urethane)s or poly(carbonate–thioimidocarbonate)s

Terpolymerization of cyclohexene oxide (CHO), CO2, and aryl isothiocyanates produced poly(carbonate–thioimidocarbonate)s with gradient character, while that of CHO, CO2, and aryl isocyanates furnished poly(carbonate–urethane)s with random sequences.

Enhancing cell-scale performance via sustained release of the varicella-zoster virus antigen from a microneedle patch under simulated microgravity.

The immune system of astronauts might become weakened in the microgravity environment in space, and the dormant varicella-zoster virus (VZV) in the body might be reactivated, seriously affecting their work and safety. For working in orbit for the long term, there is currently no efficient and durable delivery system of general vaccines in a microgravity environment. Accordingly, based on the previous foundation, we designed, modified, and synthesized a biodegradable and biocompatible copolymer, polyethylene glycol-polysulfamethazine carbonate urethane (PEG-PSCU) that could be mainly adopted to fabricate a novel sustained-release microneedle (S-R MN) patch. Compared with conventional biodegradable microneedles, this S-R MN patch could not only efficiently encapsulate protein vaccines (varicella-zoster virus glycoprotein E, VZV gE) but also further prolong the release time of VZV gE in a simulated microgravity (SMG) environment. Eventually, we verified the activation of dendritic cells by VZV gE released from the S-R MN patch in an SMG environment and the positive bioeffect of activated dendritic cells on lymphocytes using an in vitro lymph node model. This study is of great significance for the exploration of long-term specific immune responses to the VZV in an SMG environment.

Tissue formation and host remodeling of an elastomeric biodegradable scaffold in an ovine pulmonary leaflet replacement model.

In pursuit of a suitable scaffold material for cardiac valve tissue engineering applications, an acellular, electrospun, biodegradable polyester carbonate urethane urea (PECUU) scaffold was evaluated as a pulmonary valve leaflet replacement in vivo. In sheep (n = 8), a single pulmonary valve leaflet was replaced with a PECUU leaflet and followed for 1, 6, and 12 weeks. Implanted leaflet function was assessed in vivo by echocardiography. Explanted samples were studied for gross pathology, microscopic changes in the extracellular matrix, host cellular re-population, and immune responses, and for biomechanical properties. PECUU leaflets showed normal leaflet motion at implant, but decreased leaflet motion and dimensions at 6 weeks. The leaflets accumulated α-SMA and CD45 positive cells, with surfaces covered with endothelial cells (CD31+). New collagen formation occurred (Picrosirius Red). Accumulated tissue thickness correlated with the decrease in leaflet motion. The PECUU scaffolds had histologic evidence of scaffold degradation and an accumulation of pro-inflammatory/M1 and anti-inflammatory/M2 macrophages over time in vivo. The extent of inflammatory cell accumulation correlated with tissue formation and polymer degradation but was also associated with leaflet thickening and decreased leaflet motion. Future studies should explore pre-implant seeding of polymer scaffolds, more advanced polymer fabrication methods able to more closely approximate native tissue structure and function, and other techniques to control and balance the degradation of biomaterials and new tissue formation by modulation of the host immune response.

Facile and direct synthesis of oligocarbonate diols from carbon dioxide and their application as sustainable feedstock for polyurethane

Oligocarbonate diols (PPCDL) with carbonate content higher than 90% were successfully synthesized by the direct copolymerization of propylene oxide (PO) and carbon dioxide (CO2) using metal-free Lewis acid-base catalysts in the presence of 1,4-butanediol (BDO) as proton exchange agent (PEA). The effects of molar ratio of PO to BDO, temperature, pressure and reaction time on the copolymerization were systematically investigated. The molecular weight of the prepared oligocarbonate diols is in good linear relationship to PO/BDO feeding ratio and can be easily and precisely controlled in the range of 1000–4000 g mol−1. The detailed structures of the oligocarbonate diols were fully investigated by 1H NMR, 13C NMR, MALDI-TOF analysis. The rheological properties of synthesized PPCDL were also studied using a rheometer. Finally, polycarbonate urethanes were designed and successfully prepared using the PPCDLs as soft segment and 4,4′-diphenylmethane diisocyanate (MDI) and BDO as hard segment. The comprehensive evaluation of thermal and mechanical properties of the synthesized poly(carbonate urethane)s (PCUs) demonstrates their complete feasibility in the application of polyurethane industry.

Cardiac valve scaffold design: Implications of material properties and geometric configuration on performance and mechanics

Development of tissue engineered scaffolds for cardiac valve replacement is nearing clinical translation. While much work has been done to characterize mechanical behavior of native and bioprosthetic valves, and incorporate those data into models improving valve design, similar work for degradable valve scaffolds is lacking. This is particularly important given the implications mechanics have on short-term survival and long-term remodeling. As such, this study aimed to characterize spatially-resolved strain profiles on the leaflets of degradable polymeric valve scaffolds, manipulating common design features such as material stiffness by blending poly(carbonate urethane)urea with stiffer polymers, and geometric configuration, modeled after either a clinically-used valve design (Mk1 design) or an anatomically “optimized” design (Mk2 design). It was shown that material stiffness plays a significant role in overall valve performance, with the stiffest valve groups showing asymmetric and incomplete opening during systole. However, the geometric configuration had a significantly greater effect on valve performance as well as strain magnitude and distribution. Major findings in the strain maps included systolic strains having overall higher strain magnitudes than diastole, and peak radial-direction strain concentrations in the base region of Mk1 valves during systole, with a significant mitigation of radial strain in Mk2 valves. The high tunability of tissue engineered scaffolds is a great advantage for valve design, and the results reported here indicate that design parameters have significant and unequal impact on valve performance and mechanics.

Bioactive calcium phosphate coatings applied to flexible poly(carbonate urethane) foils

Long-term fixation of orthopaedic implants can be enhanced by tissue ingrowth techniques. As such, the deposition of a bioactive bone-like coating could be considered a promising method to facilitate the integration of implants onto bone tissue. In this study, we identified the optimized osteo-conductive Calcium Phosphate (CaP) coating parameters for deposition on PolyCarbonate-Urethane (PCU) foils. The oxygen plasma surface-activated PCU specimens were suspended in simulated body fluid (SBF) and supersaturated SBFs for 4 h, 8 h, 24 h, or 6 days at a temperature of 20 °C, 37 °C, or 50 °C. This resulted in semi-crystalline CaP coatings on a thin flexible foil via a one-step low-temperature aqueous technique. The deposited CaP coatings demonstrated high stability and remained intact upon bending deformation. According to the in vitro cell assessments, the conducted CaP coatings did not influence cell viability nor cell proliferation compared to the bare PCU substrate. In addition, the deposited CaP coatings enhanced the cell-mediated calcium deposition. All in all, this paper demonstrates a promising method to apply stable bioactive coatings to flexible PCU foils, which can be a promising strategy for the enhanced integration of PCU implants onto bone.

Preparation and Evaluation of Core–Shell Nanofibers Electrospun from PEU and PCL Blends via a Single-Nozzle Spinneret

The core–shell structured nanofibers are routinely fabricated by coaxial solution and single-nozzle emulsion electrospinning of two polymers. Herein, the core–shell structured polymeric nanofibers were electrospun from mixed solutions of poly(ether urethane) (PEU) with poly(ε-caprolactone) (PCL) or other biodegradable aliphatic polyesters via a single-nozzle spinneret. For comparison, the mixed solutions electrospinning of poly(carbonate urethane) (PCU) with these polyesters including PCL was also conducted. The morphologies and hierarchical structures of the as-spun nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), in vitro lipase degradation, differential scanning calorimeter (DSC), and Fourier-transform infrared (FTIR) analyses. It was shown that the blends of PEU with PCL or other biodegradable aliphatic polyesters were solely electrospun into the core–shell structured nanofibers with PEU as a shell and PCL or other biodegradable aliphatic polyesters as a core. The thickness of core/shell layers from 833/606 to 193.3/54.2 μm was adjustable by varying the feeding mass ratio from 1:3 to 3:1 of PEU to PCL or other biodegradable aliphatic polyesters. In DSC analysis, the Tonset of PEU@PCL core–shell fiber was 1.31 °C higher than that of the PCL fiber, while Tm was approximate. Furthermore, changing the electrospinning solvents of PEU with PCL or other biodegradable aliphatic polyesters retained the formation of core–shell nanofibers. In contrast, the blends of PCU with these polyesters tended to form co-continuous structured nanofibers. The effects of the physicochemical properties of mixed solutions on the charged liquid droplets, whipped jets, and morphology of the electrospun nanofibers were also inspected. The creation of core–shell nanofibers from the blends of PEU with PCL or other biodegradable aliphatic polyesters was most likely due to the interaction between the inherent thermodynamic phase separation of the polymers and their external stretching kinetic phase separation during electrospinning.

A smart polymer electrolyte coordinates the trade-off between thermal safety and energy density of lithium batteries

In this article, we develop a smart polymer electrolyte through in-situ radical random polymerization of the cyclic carbonate urethane methacrylate monomer and the 2-isocyanatoethyl methacrylate monomer, which coordinates the trade-off between thermal safety and energy density of lithium batteries. It is demonstrated that the as-developed polymer electrolyte can incur the battery thermal shutdown before reaching the thermal runaway temperature. This originates from the highly crosslinking network caused by the nucleophilic addition of carbamate to isocyanate in the polymer matrix under the elevated temperature exceeding 170 °C. Besides, superior cycle performance of 4.5 V-class LiNi0.6Co0.2Mn0.2O2/Li batteries can be achieved, with a capacity retention of 80% after 200 cycles at 0.5 C and 30 °C, owing to enhanced interface compatibility of this polymer electrolyte. Noting that this polymer electrolyte possesses a superior water-scavenging ability, which helps improve the moisture resistance and battery cycle performance. Impressively, this polymer electrolyte can achieve improved energy density and superior safety characteristic of lithium batteries under high cut-off voltage.

Dual-jet electrospun PDLGA/PCU nonwovens as promising mesh implant materials with controlled release of sirolimus and diclofenac

Dual-jet electrospinning was employed to produce two-component, partially degradable drug releasing nonwovens with interlacing of poly(D,L-lactide-co-glycolide) (PDLGA) and different poly(carbonate urethanes) (PCUs). Diclofenac sodium and sirolimus were released simultaneously from the copolyester carrier. The research focused on determining of release profiles of drugs, depending on the hydrophilicity of introduced PCU nanofibers. The influence of drugs incorporation on the hydrolytic degradation of the PDLGA and mechanical properties of nonwovens was also studied. Evaluation for interaction with cells in vitro was investigated on a fibroblast cell line in cytotoxicity and surface adhesion tests. Significant changes in drugs release rate, depending on the applied PCU were observed. It was also noticed, that hydrophilicity of drugs significantly influenced the hydrolytic degradation mechanism and surface erosion of the PDLGA, as well as the tensile strength of nonwovens. Tests carried out on cells in an in vitro experiment showed that introduction of sirolimus caused a slight reduction in the viability of fibroblasts as well as a strong limitation in their capability to colonize the surface of fibers. Due to improvement of mechanical strength and the ability to controlled drugs release, the obtained material may be considered as prospect surgical mesh implant in the treatment of hernia.

Fucoidan-loaded nanofibrous scaffolds promote annulus fibrosus repair by ameliorating the inflammatory and oxidative microenvironments in degenerative intervertebral discs

Tissue engineering holds potential in the treatment of intervertebral disc degeneration (IDD). However, implantation of tissue engineered constructs may cause foreign body reaction and aggravate the inflammatory and oxidative microenvironment of the degenerative intervertebral disc (IVD). In order to ameliorate the adverse microenvironment of IDD, in this study, we prepared a biocompatible poly (ether carbonate urethane) urea (PECUU) nanofibrous scaffold loaded with fucoidan, a natural marine bioactive polysaccharide which has great anti-inflammatory and antioxidative functions. Compared with pure PECUU scaffold, the fucoidan-loaded PECUU nanofibrous scaffold (F-PECUU) decreased the gene and protein expression related to inflammation and the oxidative stress in the lipopolysaccharide (LPS) induced annulus fibrosus cells (AFCs) significantly (p<0.05). Especially, gene expression of Il 6 and Ptgs2 was decreased more than 50% in F-PECUU with 3.0 wt% fucoidan (HF-PECUU). Moreover, the gene and protein expression related to the degradation of extracellular matrix (ECM) were reduced in a fucoidan concentration-dependent manner significantly, with increased almost 3 times gene expression of Col1a1 and Acan in HF-PECUU. Further, in a ‘box’ defect model, HF-PECUU decreased the expression of COX-2 and deposited more ECM between scaffold layers when compared with pure PECUU. The disc height and nucleus pulposus hydration of repaired IVD reached up to 75% and 85% of those in the sham group. In addition, F-PECUU helped to maintain an integrate tissue structure with a similar compression modulus to that in sham group. Taken together, the F-PECUU nanofibrous scaffolds showed promising potential to promote AF repair in IDD treatment by ameliorating the harsh degenerative microenvironment. Statement of SignificanceAnnulus fibrosus (AF) tissue engineering holds potential in the treatment of intervertebral disc degeneration (IDD), but is restricted by the inflammatory and oxidative microenvironment of degenerative disc. This study developed a biocompatible polyurethane scaffold (F-PECUU) loaded with fucoidan, a marine bioactive polysaccharide, for ameliorating IDD microenvironment and promoting disc regeneration. F-PECUU alleviated the inflammation and oxidative stress caused by lipopolysaccharide and prevented extracellular matrix (ECM) degradation in AF cells. In vivo, it promoted ECM deposition to maintain the height, water content and mechanical property of disc. This work has shown the potential of marine polysaccharides-containing functional scaffolds in IDD treatment by ameliorating the harsh microenvironment accompanied with disc degeneration.

In situ generated polymer electrolyte coating-based Janus interfaces for long-life LAGP-based NMC811/Li metal batteries

NASCION-type Li+ conductor Li1.5Al0.5Ge1.5P3O12 (LAGP) has been well considered as a promising solid-state electrolyte for solid-state lithium mental batteries (SSLMBs) by virtue of several strengths (e.g., high ionic conductivities, good stability under ambient conditions, and wide electrochemical stability windows). However, there are rare reports concerning the utilization of LAGP-based solid electrolytes in the high-voltage LiNi0.8Mn0.1Co0.1O2 (NMC811)/Li metal cell. This can be ascribed to the fact that the mechanochemically stable interface toward Li metal anodes and compatible interface close to NMC811 cathodes cannot be simultaneously achieved. To address this, herein, a LAGP-type solid electrolyte with in situ generated polymer electrolyte coating-based Janus interfaces is developed. The as-developed solid electrolyte is prepared by coating LAGP with in situ crosslinked polymethyl methacrylate and poly(cyclic carbonate urethane methacrylate)-based polymer electrolytes toward lithium anode and NMC811 cathode, respectively. It is demonstrated that the as-developed solid electrolyte can achieve both compatible electrode–electrolyte interphases. As a result, this solid electrolyte endows 4.3 V and 4.5 V-class NMC811/Li batteries with superior cycling stability. Our work provides a good paradigm to address the interfacial issues confronting solid state electrolyte chemistries.

Dual-jet electrospun PDLGA/PCU nonwovens and their mechanical and hydrolytic degradation properties

A dual-jet electrospinning was used to mix a different hydrophilicity poly(carbonate urethanes) (PCUs) nanofibers with a biodegradable poly(D,L-lactide-co-glycolide) (PDLGA) copolyester microfibers. As a result, PDLGA/PCU partially degradable nonwovens consisting of an interlaced of both components fibers were obtained. In order to examine the hydrolytic degradation process of polyester fraction, as well as changes that occurred in the mechanical properties of the whole nonwovens, gel permeation chromatography, proton nuclear magnetic resonance spectroscopy, differential scanning calorimetry and scanning electron microscopy as well as static tensile test were performed. Obtained results showed that for the introduction of more hydrophobic PCU nanofibers (ChronoSil), the process of copolyester chain scission slowed down and the erosion mechanism proceeded in bulk. Unexpectedly, even greater deceleration of PDLGA fibers degradation was observed in case of more hydrophilic PCU (HydroThane), and erosion mechanism changed to surface. Enhancement the affinity of the whole nonwoven to the water, manifested by strong water uptake, facilitated the diffusion processes of both: water and acid degradation by-products, which limited autocatalysis reactions of the hydrolysis of ester bonds. On the other hand, strength tests showed the synergy in the mechanical characteristics of both components. Presented method allows influencing the mechanism and rate of polyester degradation without changing its chemical composition and physical properties, affecting only the physical interactions between the nonwoven and the degradation environment, and thus, on diffusion processes. Obtained partially degradable materials possessed also time prolonged functional properties, compared to the copolyester-only nonwoven itself, thus could be considered as promising for biomedical applications e.g. in drug release systems, implants or surgical meshes for supporting soft tissues.

The experimental study of regeneration of annulus fibrosus using decellularized annulus fibrosus matrix/poly(ether carbonate urethane)urea-blended fibrous scaffolds with varying elastic moduli.

Although tissue engineering has attracted increasing attention for the treatment of degenerative intervertebral disc disease, the biochemical properties, structural organization, and mechanical characteristics of annulus fibrosus tissue have restricted progress. Differentiation of annulus fibrosus-derived stem cells (AFSCs) can be regulated by the elasticity of substrates such as poly(ether carbonate urethane)urea (PECUU). Decellularized annulus fibrosus matrix (DAFM) has good biocompatibility and biodegradability, making it suitable for cell adhesion, proliferation, and differentiation. In this study, we used a coaxial electrospinning method to synthesize DAFM/PECUU-blended fibrous scaffolds with elasticities approximating that of native inner and outer annulus fibrosus tissue. AFSCs cultured on DAFM/PECUU-blended fibrous scaffolds exhibited increased collagen type I gene expression with increasing elasticity of the scaffold material; notably, collagen type II and aggrecan gene expression exhibited the opposite trend. Regarding extracellular matrix secretion, collagen type I content gradually increased with substrate elasticity, while collagen type II and aggrecan contents decreased. In vivo evaluations employing magnetic resonance imaging, hematoxylin and eosin staining, and immunohistochemistry indicated that DAFM/PECUU-blended fibrous scaffolds could effectively repair defects of annulus fibrosus tissue. Our findings provide a theoretical and practical basis for the development of bionic annulus fibrosus tissue that closely mimics the biological properties, mechanical function, and matrix composition of native tissue.

Anisotropic elastic behavior of a hydrogel-coated electrospun polyurethane: Suitability for heart valve leaflets

Although xenograft biomaterials have been used for decades in replacement heart valves, they continue to face multiple limitations, including limited durability, mineralization, and restricted design space due to their biological origins. These issues necessitate the need for novel replacement heart valve biomaterials that are durable, non-thrombogenic, and compatible with transcatheter aortic valve replacement devices. In this study, we explored the suitability of an electrospun poly(carbonate urethane) (ES-PCU) mesh coated with a poly(ethylene glycol) diacrylate (PEGDA) hydrogel as a synthetic biomaterial for replacement heart valve leaflets. In this material design, the mesh provides the mechanical support, while the hydrogel provides the required surface hemocompatibility. We conducted a comprehensive study to characterize the structural and mechanical properties of the uncoated mesh as well as the hydrogel-coated mesh (composite biomaterial) over the estimated operational range. We found that the composite biomaterial was functionally robust with reproducible stress–strain behavior within and beyond the functional ranges for replacement heart valves, and was able to withstand the rigors of mechanical evaluation without any observable damage. In addition, the composite biomaterial displayed a wide range of mechanical anisotropic responses, which were governed by fiber orientation of the mesh, which in turn, was controlled with the fabrication process. Finally, we developed a novel constitutive modeling approach to predict the mechanical behavior of the composite biomaterial under in-plane extension and shear deformation modes. This model identified the existence of fiber–fiber mechanical interactions in the mesh that have not previously been reported. Interestingly, there was no evidence of fiber–hydrogel mechanical interactions. This important finding suggests that the hydrogel coating can be optimized for hemocompatibility independent of the structural mechanical responses required by the leaflet. This initial study indicated that the composite biomaterial has mechanical properties well-suited for replacement heart valve applications and that the electrospun mesh microarchitecture and hydrogel biological properties can be optimized independently. It also reveals that the structural mechanisms contributing to the mechanical response are more complicated than what was previously established and paves the pathway for more detailed future studies.

Role of Graphene Oxide on the Mechanical Behaviour of Polycarbonate-Urethane/Graphene Oxide Composites

A new generation of carbon-based materials such as graphene and graphene oxide (GO) have been widely studied due to their potential in a variety of applications including biomedical materials and devices. This work investigates the appropriate GO morphology and content to be used as a filler for a poly(carbonate urethane) (PCU) polymer in order to mechanical properties improvements. Two graphene oxides with different levels of oxidation and morphology were blended into a PCU matrix to obtain high mechanical performance and good flexibility. Nanocomposites of PCU and GO were produced with a filler content of 0.2 wt%, 0.4 wt%, and 2.0 wt%. Polymeric membranes were obtained using solvent evaporation and characterised by their thermal properties (Differential Scanning Calorimetry), thermo-mechanical (Dynamic-Mechanical Thermal Analysis), and mechanical test results (tensile). The results indicated that GO platelets tend to interact strongly with the hard segments (HS) of PCU chains due to the polar chemical similarity of GO and HS structures. Two mechanical behaviours were found for the PCU/GO-2 nanocomposites, at small and large deformations. Improvements in the Secant Modulus and values of stress until 350% of strain are observed for low filler content while high filler content is needed for improvements at break point (stress and strain). PCU/GO nanocomposites with high mechanical performance can be produced by adjusting the GO content and characteristics to reach different application possibilities.

Regeneration of annulus fibrosus tissue using a DAFM/PECUU-blended electrospun scaffold

Low back pain and disc degeneration affect quality of life and imposes an enormous financial burden. Although annulus fibrosus (AF) tissue engineering provides an alternative therapeutic possibility in the treatment of degenerative intervertebral disc disease, it is restricted by the biochemical properties, organizational structure, and mechanical characteristics of the scaffold. The ideal scaffold should closely mimic the natural extracellular matrix (ECM) in structure and function for long-term stability and survival. Poly(ether carbonate urethane) urea (PECUU) can be electrospun into nanofibrous scaffolds to mimic ECM architecture with the appropriate mechanical properties. However, PECUU scaffolds lack the bioactivity of natural ECM. On the other hand, a decellularized annulus fibrosus matrix (DAFM) has good biocompatibility and biodegradability and has been shown to promote secretion of AF-related ECM. Herein, DAFM/PECUU-blended electrospun scaffolds were fabricated with the help of coaxial electrospinning technology for the first time. AF-derived stem cells were cultured on DAFM/PECUU electrospun scaffolds, and cellular metabolic activity, morphology, and gene expression assays as well as AF-related ECM synthesis were performed. The results showed that AF-derived stem cells proliferated well on the scaffolds. Gene expression and ECM secretion of collagen type I and II and aggrecan from AF-derived stem cells cultured on DAFM/PECUU electrospun scaffolds were higher than from those on PECUU fibrous scaffolds. Thus, DAFM/PECUU electrospun scaffolds are a potential candidate for AF tissue engineering applications.

Adipose-derived stem cell sheet under an elastic patch improves cardiac function in rats after myocardial infarction

ObjectivesAlthough adipose-derived stem cells (ADSCs) have shown promise in cardiac regeneration, stable engraftment is still challenging. Acellular bioengineered cardiac patches have shown promise in positively altering ventricular remodeling in ischemic cardiomyopathy. We hypothesized that combining an ADSC sheet approach with a bioengineered patch would enhance ADSC engraftment and positively promote cardiac function compared with either therapy alone in a rat ischemic cardiomyopathy model. MethodsCardiac patches were generated from poly(ester carbonate urethane) urea and porcine decellularized cardiac extracellular matrix. ADSCs constitutively expressing green fluorescent protein were established from F344 rats and transplanted as a cell sheet over the left ventricle 3 days after left anterior descending artery ligation with or without an overlying cardiac patch. Cardiac function was serially evaluated using echocardiography for 8 weeks, comparing groups with combined cells and patch (group C, n = 9), ADSCs alone (group A, n = 7), patch alone (group P, n = 6) or sham groups (n = 7). ResultsMuch greater numbers of ADSCs survived in the C versus A groups (P < .01). At 8 weeks posttransplant, the percentage fibrotic area was lower (P < .01) in groups C and P compared with the other groups and vasculature in the peri-infarct zone was greater in group C versus other groups (P < .01), and hepatocyte growth factor expression was higher in group C than in other groups (P < .05). Left ventricular ejection fraction was higher in group C versus other groups. ConclusionsA biodegradable cardiac patch enhanced ADSC engraftment, which was associated with greater cardiac function and neovascularization in the peri-infarct zone following subacute myocardial infarction.

Substrate Topography Regulates Differentiation of Annulus Fibrosus-Derived Stem Cells via CAV1-YAP-Mediated Mechanotransduction

Regeneration of annulus fibrosus (AF) through tissue engineering techniques shows promise as a treatment for patients with degenerative disc disease (DDD). Yet, it remains challenging because of the intrinsic heterogeneity of AF tissue and shortage of in-depth knowledge of its structure-function correlation. In the current study, we fabricated fibrous poly(ether carbonate urethane)urea (PECUU) scaffolds with various fiber sizes to mimic the microstructural feature of native AF and aimed to regulate the differentiation of AF-derived stem cells (AFSCs) by controlling the topographical cues of the scaffold. We found that the morphology of AFSCs varied significantly on scaffolds with various fiber sizes. Meanwhile, the expression of the phenotypic marker genes of outer AF was up-regulated on scaffolds with large fibers. Meanwhile, enhanced expression of the phenotypic marker genes of inner AF was seen on scaffolds with small fibers. Such topography-dependent gene expression in AFSCs approximated the biochemical profile of AF tissue in various zones. Moreover, cell spreading and nucleus translocation of Yes-associated protein (YAP) were facilitated with increased fiber size. Formation and maturation of focal adhesions of AFSCs were also promoted. We also found that Caveolin-1 (CAV1) positively modulated the mechano-responses of YAP in response to substrate topography. In conclusion, depending on the activation of the CAV1-YAP mechanotransduction axis, tuning the fiber size of scaffolds can effectively induce changes in cell shape, adhesions, and extracellular matrix expression. This work may therefore provide new insights in the design of novel materials toward AF tissue regeneration.

A Polymer-Reinforced SEI Layer Induced by a Cyclic Carbonate-Based Polymer Electrolyte Boosting 4.45 V LiCoO2 /Li Metal Batteries.

Lithium (Li) metal batteries (LMBs) are enjoying a renaissance due to the high energy densities. However, they still suffer from the problem of uncontrollable Li dendrite and pulverization caused by continuous cracking of solid electrolyte interphase (SEI) layers. To address these issues, developing spontaneously built robust polymer-reinforced SEI layers during electrochemical conditioning can be a simple yet effective solution. Herein, a robust homopolymer of cyclic carbonate urethane methacrylate is presented as the polymer matrix through an in situ polymerization method, in which cyclic carbonate units can participate in building a stable polymer-integrated SEI layer during cycling. The as-investigated gel polymer electrolyte (GPE) assembled LiCoO2 /Li metal batteries exhibit a fantastic cyclability with a capacity retention of 92% after 200 cycles at 0.5 C (1 C = 180 mAh g-1 ), evidently exceeding that of the counterpart using liquid electrolytes. It is noted that the anionic ring-opening polymerization of the cyclic carbonate units on the polymer close to the Li metal anodes enables a mechanically reinforced SEI layer, thus rendering excellent compatibility with Li anodes. The in situ formed polymer-reinforced SEI layers afford a splendid strategy for developing high voltage resistant GPEs compatible with Li metal anodes toward high energy LMBs.