Lipase-Catalyzed Synthesis and Characterization of Poly(glycerol sebacate).

This study demonstrated that immobilized Candida antarctica lipase B (N435) catalysis in bulk leads to higher molecular weight poly(glycerol sebacate), PGS, than self-catalyzed condensation polymerization. Since the glass-transition temperature, fragility, modulus, and strength for rubbery networks are inversely dependent on the concentration of chain ends, higher molecular weight PGS prepolymers will enable the preparation of cross-linked PGS matrices with unique mechanical properties. The evolution of molecular species during the prepolymerization step conducted at 120 °C for 24 h, prior to enzyme addition, revealed regular decreases in sebacic acid and glycerol-sebacate dimer with corresponding increases in oligomers with chain lengths from 3 to 7 units such that a homogeneous liquid substrate has resulted. At 67 h, for N435-catalyzed PGS synthesis, the carboxylic acid conversion reached 82% without formation of a gel fraction, and number-average molecular weight (Mn) and weight-average molecular weight (Mw) values reached 6000 and 59 400 g/mol, respectively. In contrast, self-catalyzed PGS condensation polymerizations required termination at 55 h to avoid gelation, reached 72% conversion, and Mn and Mw values of 2600 and 13 800 g/mol, respectively. We also report the extent that solvent fractionation can enrich PGS in higher molecular weight chains. The use of methanol as a nonsolvent increased Mn and Mw by 131.7 and 18.3%, respectively, and narrower dispersity (D) decreased by 47.7% relative to the nonfractionated product.

PGS/HAp Microporous Composite Scaffold Obtained in the TIPS-TCL-SL Method: An Innovation for Bone Tissue Engineering.

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (1H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1ß, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.

Characterizing Cross-Linking Within Polymeric Biomaterials in the SEM by Secondary Electron Hyperspectral Imaging.

A novel capability built upon secondary electron (SE) spectroscopy provides an enhanced cross-linking characterization toolset for polymeric biomaterials, with cross-linking density and variation captured at a multiscale level. The potential of SE spectroscopy for material characterization has been investigated since 1947. The absence of suitable instrumentation and signal processing proved insurmountable barriers to applying SE spectroscopy to biomaterials, and consequently, capturing SE spectra containing cross-linking information is a new concept. To date, cross-linking extent is inferred from analytical techniques such as nuclear magnetic resonance (NMR), differential scanning calorimetry, and Raman spectroscopy (RS). NMR provides extremely localized information on the atomic scale and molecular scale, while RS information volume is on the microscale. Other methods for the indirect study of cross-linking are bulk mechanical averaging methods, such as tensile and compression modulus testing. However, these established averaging methods for the estimation of polymer cross-linking density are incomplete because they fail to provide information of spatial distributions within the biomaterial morphology across all relevant length scales. The efficacy of the SE spectroscopy capability is demonstrated in this paper by the analysis of poly(glycerol sebacate)-methacrylate (PGS-M) at different degrees of methacrylation delivering new insights into PGS-M morphology.

Characterization of a New Mixture of Mono-Rhamnolipids Produced by Pseudomonas gessardii Isolated from Edmonson Point (Antarctica).

Rhamnolipids (RLs) are surface-active molecules mainly produced by Pseudomonas spp. Antarctica is one of the less explored places on Earth and bioprospecting for novel RL producer strains represents a promising strategy for the discovery of novel structures. In the present study, 34 cultivable bacteria isolated from Edmonson Point Lake, Ross Sea, Antarctica were subjected to preliminary screening for the biosurfactant activity. The positive strains were identified by 16S rRNA gene sequencing and the produced RLs were characterized by liquid chromatography coupled to high resolution mass spectrometry (LC-HRESIMS) and liquid chromatography coupled with tandem spectrometry (LC-MS/MS), resulting in a new mixture of 17 different RL congeners, with six previously undescribed RLs. We explored the influence of the carbon source on the RL composition using 12 different raw materials, such as monosaccharides, polysaccharides and petroleum industry derivatives, reporting for the first time the production of RLs using, as sole carbon source, anthracene and benzene. Moreover, we investigated the antimicrobial potential of the RL mixture, towards a panel of both Gram-positive and Gram-negative pathogens, reporting very interesting results towards Listeria monocytogenes with a minimum inhibitory concentration (MIC) value of 3.13 µg/mL. Finally, we report for the first time the antimicrobial activity of RLs towards three strains of the emerging multidrug resistant Stenotrophomonas maltophilia with MIC values of 12.5 µg/ml.

Enzymatic Synthesis of Glucose Monodecanoate in a Hydrophobic Deep Eutectic Solvent.

Environmentally friendly and biodegradable reaction media are an important part of a sustainable glycolipid production in the transition to green chemistry. Deep eutectic solvents (DESs) are an ecofriendly alternative to organic solvents. So far, only hydrophilic DESs were considered for enzymatic glycolipid synthesis. In this study, a hydrophobic DES consisting of (-)-menthol and decanoic acid is presented for the first time as an alternative to hydrophilic DES. The yields in the newly introduced hydrophobic DES are significantly higher than in hydrophilic DESs. Different reaction parameters were investigated to optimize the synthesis further. Twenty milligrams per milliliter iCalB and 0.5 M glucose resulted in the highest initial reaction velocity for the esterification reaction, while the highest initial reaction velocity was achieved with 1.5 M glucose in the transesterification reaction. The enzyme was proven to be reusable for at least five cycles without significant loss of activity.

Highly aligned and geometrically structured poly(glycerol sebacate)-polyethylene oxide composite fiber matrices towards bioscaffolding applications.

The biocompatible and biodegradable polymer poly(glycerol sebacate), or PGS, is a rubber-like material that finds use in several biomedical applications. PGS is often cast into a mold to form desired structures; alternatively, blending PGS with other reinforcing polymers produces viscous solutions that can be spun into non-woven fibrous scaffolds. For tissue scaffolding applications, ordered fibrous matrices are advantageous and have been shown to promote cell orientation and proliferation by contact guidance, providing topographical cues for the seeded cells. The development of techniques for easily producing aligned fibrous matrices is therefore a priority. PGS nanofibers have been fabricated successfully using electrospinning techniques. For producing PGS microfibers, we introduce the electro-less STRAND (Substrate Translation and Rotation for Aligned Nanofiber Deposition) process as an alternative to electrospinning. STRAND provides superior control of fiber properties including diameter, alignment, spacing, and therefore deposition density by mechanically drawing polymer fibers from solution. The goal in using this method is the simple production of aligned PGS fiber matrices for retinal tissue scaffolding.

Biomimetic poly(glycerol sebacate)/polycaprolactone blend scaffolds for cartilage tissue engineering.

Poly (glycerol sebacate) (PGS) is a synthetic polymeric material with the characteristics of controllable degradation, high plasticity and excellent biocompatibility. However, the time of PGS degradation is faster than that of cartilage regeneration, which limits its application in cartilage tissue engineering. Polycaprolactone (PCL), a widely used synthetic polymer, has appropriate biodegradability and higher mechanical strength. This study aims to make a scaffold from blends of fast degrading PGS and slowly degrading PCL, and to investigate its potential for cartilage tissue engineering applications. Scanning electron microscopic analysis indicated that the scaffolds provided favourable porous microstructures. In vitro degradation test showed that PGS/ PCL scaffolds acquired longer degradation time and better mechanical strength. PGS/PCL scaffolds seeded with Bone marrow-derived mesenchymal stem cells (BMSCs) and articular chondrocytes (ACCs) were cultured in vitro. Short-term in vitro experiments confirmed that both seeded cells could adhere and proliferate on the scaffold. Chondrogenic culture for cell-scaffold constructs confirmed BMSCs could differentiate into chondrocyte-like cells in PGS/PCL scaffolds. With tunable biodegradation, favorable mechanical properties and cytocompatibility, PGS/PCL scaffolds would potentially be suitable for the regeneration of cartilage tissue. Poly (glycerol sebacate) (PGS) is a synthetic polymeric material with the characteristics of controllable degradation, high plasticity and good biocompatibility. However, the time of PGS degradation is faster than that of cartilage regeneration, which limits its application in cartilage tissue engineering. Polycaprolactone(PCL), a widely used synthetic polymer, has appropriate biodegradability. This study aims to make a scaffold from blends of fast degrading PGS and slowly degrading PCL, and to investigate its potential for cartilage tissue engineering applications. Scanning electron microscopic analysis indicated that the scaffolds provided favourable porous microstructures. In vitro degradation test showed that PGS/ PCL scaffolds got longer degradation time with surface degradation nature. PGS/PCL scaffolds seeded with Bone marrow-derived mesenchymal stem cells (BMSCs) and articular chondrocytes (ACCs) were cultured in vitro under the same condition. Short-term in vitro experiments confirmed that both seed cells could adhere and proliferate on the scaffold. Chondrogenic culture for cell-scaffold constructs confirmed BMSCs could differentiate into chondrocyte-like cells and form cartilage-specific matrix in PGS/PCL scaffolds. With cytocompatibility and biodegradation profile, PGS/PCL scaffolds get great potential for cartilage tissue engineering.

Mesenchymal Cells Affect Salivary Epithelial Cell Morphology on PGS/PLGA Core/Shell Nanofibers.

Engineering salivary glands is of interest due to the damaging effects of radiation therapy and the autoimmune disease Sjögren's syndrome on salivary gland function. One of the current problems in tissue engineering is that in vitro studies often fail to predict in vivo regeneration due to failure of cells to interact with scaffolds and of the single cell types that are typically used for these studies. Although poly (lactic co glycolic acid) (PLGA) nanofiber scaffolds have been used for in vitro growth of epithelial cells, PLGA has low compliance and cells do not penetrate the scaffolds. Using a core-shell electrospinning technique, we incorporated poly (glycerol sebacate) (PGS) into PLGA scaffolds to increase the compliance and decrease hydrophobicity. PGS/PLGA scaffolds promoted epithelial cell penetration into the scaffold and apical localization of tight junction proteins, which is necessary for epithelial cell function. Additionally, co-culture of the salivary epithelial cells with NIH3T3 mesenchymal cells on PGS/PLGA scaffolds facilitated epithelial tissue reorganization and apical localization of tight junction proteins significantly more than in the absence of the mesenchyme. These data demonstrate the applicability of PGS/PLGA nanofibers for epithelial cell self-organization and facilitation of co-culture cell interactions that promote tissue self-organization in vitro.

New vinylester-based monoliths as a new stationary phase for capillary electrochromatography.

Vinyl ester-based monoliths are proposed as a new group of stationary phase for CEC. The capillary monolithic columns were prepared by using two vinyl ester monomers, vinyl pivalate (VPV), and vinyl decanoate (VDC) by using ethylene dimethacrylate (EDMA) as the cross-linking agent, and 2-acrylamido-2-methylpropane sulfonic acid as the charge-bearing monomer. The monoliths with different pore structures and permeabilities were obtained by varying the type and composition of the porogen mixture containing isoamyl alcohol and 1,4-butanediol. The electrochromatographic separation of alkylbenzenes was successfully performed by using an acetonitrile/aqueous buffer system as the mobile phase in a CEC system. Vinyl ester monoliths with short alkyl chain length (i.e. poly(VPV-co-EDMA) exhibited better separation performance compared with the monolith with long alkyl chain length (i.e. poly(VDC-co-EDMA). In the case of VPV-based monoliths, the theoretical plate numbers higher than 250 000 plates/m were achieved by using a porogen mixture containing 33% v/v of isoamyl alcohol. For both VDC and VPV-based monoliths, the column efficiency was almost independent of the superficial velocity in the range of 2-12 cm/min.

Rapid homogeneous endothelialization of high aspect ratio microvascular networks.

Microvascularization of an engineered tissue construct is necessary to ensure the nourishment and viability of the hosted cells. Microvascular constructs can be created by seeding the luminal surfaces of microfluidic channel arrays with endothelial cells. However, in a conventional flow-based system, the uniformity of endothelialization of such an engineered microvascular network is constrained by mass transfer of the cells through high length-to-diameter (L/D) aspect ratio microchannels. Moreover, given the inherent limitations of the initial seeding process to generate a uniform cell coating, the large surface-area-to-volume ratio of microfluidic systems demands long culture periods for the formation of confluent cellular microconduits. In this report, we describe the design of polydimethylsiloxane (PDMS) and poly(glycerol sebacate) (PGS) microvascular constructs with reentrant microchannels that facilitates rapid, spatially homogeneous endothelial cell seeding of a high L/D (2 cm/35 µm; > 550:1) aspect ratio microchannels. MEMS technology was employed for the fabrication of a monolithic, elastomeric, reentrant microvascular construct. Isotropic etching and PDMS micromolding yielded a near-cylindrical microvascular channel array. A 'stretch - seed - seal' operation was implemented for uniform incorporation of endothelial cells along the entire microvascular area of the construct yielding endothelialized microvascular networks in less than 24 h. The feasibility of this endothelialization strategy and the uniformity of cellularization were established using confocal microscope imaging.

Criteria for Quick and Consistent Synthesis of Poly(glycerol sebacate) for Tailored Mechanical Properties.

Poly(glycerol sebacate) (PGS) and its derivatives make up an attractive class of biomaterial owing to their tunable mechanical properties with programmable biodegradability. In practice, however, the application of PGS is often hampered by frequent inconsistency in reproducing process conditions. The inconsistency stems from the volatile nature of glycerol during the esterification process. In this study, we suggest that the degree of esterification (DE) can be used to predict precisely the physical status, the mechanical properties, and the degradation of the PGS materials. Young's modulus is shown to linearly increase with DE, which is in agreement with an entropic spring theory of rubbers. To provide a processing guideline for researchers, we also provide a physical status map as a function of curing temperature and time. The amount of glycerol loss, obtainable by monitoring the evolution of the total mass loss and the DE during synthesis, is shown to make the predictions even more precise. We expect that these strategies can be applicable to different categories of polymers that involve condensation polymerization with the volatility of the reactants. In addition, we demonstrate that microwave-assisted prepolymerization is a time- and energy-efficient pathway to obtain PGS. For example, 15 min of microwave time is shown to be as efficient as prepolymerization in nitrogen atmosphere for 6 h at 130 °C. The quick synthesis method, however, causes a severe evaporation of glycerol, resulting in a large distortion in the monomer ratio between glycerol and sebacic acid. Consequently, more rigid PGS is produced under a similar curing condition compared to the conventional prepolymerization method. Finally, we demonstrate that the addition of molecularly rigid cross-linking agents and network-structured inorganic nanoparticles are also effective in enhancing the mechanical properties of the PGS-derived materials.

Dynamics of fatty acid vesicles in response to pH stimuli.

We investigate the dynamics of decanoic acid/decanoate (DA) vesicles in response to pH stimuli. Two types of dynamic processes induced by the micro-injection of NaOH solutions are sequentially observed: deformations and topological transitions. In the deformation stage, DA vesicles show a series of shape deformations, i.e., prolate-oblate-stomatocyte-sphere. In the topological transition stage, spherical DA vesicles follow either of the two pathways, pore formation and vesicle fusion. The pH stimuli modify a critical aggregation concentration of DA molecules, which causes the solubilization of DA molecules in the outer leaflet of the vesicle bilayers. This solubilization decreases the outer surface area of the vesicle, thereby increasing surface tension. A kinetic model based on area difference elasticity theory can accurately describe the dynamics of DA vesicles triggered by pH stimuli.

Altering the activation mechanism in Thermomyces lanuginosus lipase.

It is shown by rational site-directed mutagenesis of the lid region in Thermomyces lanuginosus lipase that it is possible to generate lipase variants with attractive features, e.g., high lipase activity, fast activation at the lipid interface, ability to act on water-soluble substrates, and enhanced calcium independence. The rational design was based on the lid residue composition in Aspergillus niger ferulic acid esterase (FAEA). Five constructs included lipase variants containing the full FAEA lid, a FAEA-like lid, an intermediate lid of FAEA and TlL character, and the entire lid region from Aspergillus terreus lipase (AtL). To investigate an altered activation mechanism for each variant compared to that of TlL, a combination of activity- and spectroscopic-based measurements were applied. The engineered variant with a lid from AtL displayed interfacial activation comparable to that of TlL, whereas variants with FAEA lid character showed interfacial activation independence with pronounced activity toward pNP-acetate and pNP-butyrate below the critical micelle concentration. For variants with lipase and esterase character, lipase activity measurements further indicated a faster activation at the lipid interface. Relative to their activity toward pNP-ester substrates in calcium-rich buffer, all lid variants retained between 15 and 100% activity in buffer containing 5 mM EDTA whereas TlL activity was reduced to less than 2%, demonstrating the lid's central role in governing calcium dependency. For FAEA-like lid variants, accessible hydrophobic surface area measurements showed an approximate 10-fold increase in the level of binding of extrinsic fluorophores to the protein surface relative to that of TlL accompanied by a blue shift in emission indicative of an open lid in aqueous solution. Together, these studies report on the successful alteration of the activation mechanism in TlL by rational design creating novel lipases with new, intriguing functionalities.

Chemical composition and biological activities of Gerbera anandria.

Gerbera anandria (Compositae) was extracted with 75% ethanol and the residue was fractionated using light petroleum, chloroform and ethyl acetate. The constituents of the extracts were separated by column chromatography employing solvents of different polarity. Column chromatography of the light petroleum fraction resulted in the isolation of methyl hexadecanoate, while the chloroform fraction afforded xanthotoxin, 2-hydroxy-6-methylbenzoic acid, 7-hydroxy-1(3H)-isobenzofuranone, a mixture of ß-sitosterol and stigmasterol, and 8-methoxysmyrindiol and the ethyl acetate fraction gave gerberinside, apigenin-7-O-ß-d-glucopyranoside and quercetin. A new coumarin, 8-methoxysmyrindiol, was found. The chemical structures of the isolated compounds were established by MS and NMR (HSQC, HMBC). Free radical scavenging and cytotoxic activities of crude extracts and 8-methoxysmyrindiol were further investigated. The ethyl acetate phase exerted the strongest DPPH free radical scavenging activity in comparison to the other fractions. The coumarin 8-methoxysmyrindiol demonstrated cytotoxicity against multiple human cancer cell lines, with the highest potency in HepG2 cells.

An Encapsulation-Free and Hierarchical Porous Triboelectric Scaffold with Dynamic Hydrophilicity for Efficient Cartilage Regeneration.

Tissue engineering and electrotherapy are two promising methods to promote tissue repair. However, their integration remains an underexplored area, because their requirements on devices are usually distinct. Triboelectric nanogenerators (TENGs) have shown great potential to develop self-powered devices. However, due to their susceptibility to moisture, TENGs have to be encapsulated in vivo. Therefore, existing TENGs cannot be employed as tissue engineering scaffolds, which require direct interaction with surrounding cells. Here, the concept of triboelectric scaffolds (TESs) is proposed. Poly(glycerol sebacate), a biodegradable and relatively hydrophobic elastomer, is selected as the matrix of TESs. Each hydrophobic micropore in multi-hierarchical porous TESs efficiently serves as a moisture-resistant working unit of TENGs. Integration of tons of micropores ensures the electrotherapy ability of TESs in vivo without encapsulation. Originally hydrophobic TESs are degraded by surface erosion and transformed into hydrophilic surfaces, facilitating their role as tissue engineering scaffolds. Notably, TESs seeded with chondrocytes obtain dense and large matured cartilages after subcutaneous implantation in nude mice. Importantly, rabbits with osteochondral defects receiving TES implantation show favorable hyaline cartilage regeneration and complete cartilage healing. This work provides a promising electronic biomedical device and will inspire a series of new in vivo applications.

Wireless electrostimulation for cancer treatment: An integrated nanoparticle/coaxial fiber mesh platform.

Cancer, namely breast and prostate cancers, is the leading cause of death in many developed countries. Controlled drug delivery systems are key for the development of new cancer treatment strategies, to improve the effectiveness of chemotherapy and tackle off-target effects. In here, we developed a biomaterials-based wireless electrostimulation system with the potential for controlled and on-demand release of anti-cancer drugs. The system is composed of curcumin-loaded poly(3,4-ethylenedioxythiophene) nanoparticles (CUR/PEDOT NPs), encapsulated inside coaxial poly(glycerol sebacate)/poly(caprolactone) (PGS/PCL) electrospun fibers. First, we show that the PGS/PCL nanofibers are biodegradable, which allows the delivery of NPs closer to the tumoral region, and have good mechanical properties, allowing the prolonged storage of the PEDOT NPs before their gradual release. Next, we demonstrate PEDOT/CUR nanoparticles can release CUR on-demand (65 % of release after applying a potential of -1.5 V for 180 s). Finally, a wireless electrostimulation platform using this NP/fiber system was set up to promote in vitro human prostate cancer cell death. We found a decrease of 67 % decrease in cancer cell viability. Overall, our results show the developed NP/fiber system has the potential to effectively deliver CUR in a highly controlled way to breast and prostate cancer in vitro models. We also show the potential of using wireless electrostimulation of drug-loaded NPs for cancer treatment, while using safe voltages for the human body. We believe our work is a stepping stone for the design and development of biomaterial-based future smarter and more effective delivery systems for anti-cancer therapy.

Enhanced wound regeneration by PGS/PLA fiber dressing containing platelet-rich plasma: an in vitro study.

Novel wound dressings with therapeutic effects are being continually designed to improve the wound healing process. In this study, the structural, chemical, physical, and biological properties of an electrospun poly glycerol sebacate/poly lactide acid/platelet-rich plasma (PGS/PLA-PRP) nanofibers were evaluated to determine its impacts on in vitro wound healing. Results revealed desirable cell viability in the Fibroblast (L929) and macrophage (RAW-264.7) cell lines as well as human umbilical vein endothelial cells (HUVEC). Cell migration was evident in the scratch assay (L929 cell line) so that it promoted scratch contraction to accelerate in vitro wound healing. Moreover, addition of PRP to the fiber structure led to enhanced collagen deposition (~ 2 times) in comparison with PGS/PLA scaffolds. While by addition PRP to PGS/PLA fibers not only decreased the expression levels of pro-inflammatory cytokines (IL-6 and TNF-α) in RAW-264.7 cells but also led to significantly increased levels of cytokine (IL-10) and the growth factor (TGF-ß), which are related to the anti-inflammatory phase (M2 phenotype). Finally, PGS/PLA-PRP was found to induce a significant level of angiogenesis by forming branching points, loops, and tubes. Based on the results obtained, the PGS/PLA-PRP dressing developed might be a promising evolution in skin tissue engineering ensuring improved wound healing and tissue regeneration.

A bioenergetically-active ploy (glycerol sebacate)-based multiblock hydrogel improved diabetic wound healing through revitalizing mitochondrial metabolism.

Diabetic wounds impose significant burdens on patients' quality of life and healthcare resources due to impaired healing potential. Factors like hyperglycemia, oxidative stress, impaired angiogenesis and excessive inflammation contribute to the delayed healing trajectory. Mounting evidence indicates a close association between impaired mitochondrial function and diabetic complications, including chronic wounds. Mitochondria are critical for providing energy essential to wound healing processes. However, mitochondrial dysfunction exacerbates other pathological factors, creating detrimental cycles that hinder healing. This study conducted correlation analysis using clinical specimens, revealing a positive correlation between mitochondrial dysfunction and oxidative stress, inflammatory response and impaired angiogenesis in diabetic wounds. Restoring mitochondrial function becomes imperative for developing targeted therapies. Herein, we synthesized a biodegradable poly (glycerol sebacate)-based multiblock hydrogel, named poly (glycerol sebacate)-co-poly (ethylene glycol)-co-poly (propylene glycol) (PEPGS), which can be degraded in vivo to release glycerol, a crucial component in cellular metabolism, including mitochondrial respiration. We demonstrate the potential of PEPGS-based hydrogels to improve outcomes in diabetic wound healing by revitalizing mitochondrial metabolism. Furthermore, we investigate the underlying mechanism through proteomics analysis, unravelling the regulation of ATP and nicotinamide adenine dinucleotide metabolic processes, biosynthetic process and generation during mitochondrial metabolism. These findings highlight the therapeutic potential of PEPGS-based hydrogels as advanced wound dressings for diabetic wound healing.

Reconfigurable biodegradable shape-memory elastomers via Diels-Alder coupling.

Synthetic biodegradable elastomers are a class of polymers that have demonstrated far-reaching utility as biomaterials for use in many medical applications. Biodegradable elastomers can be broadly classified into networks prepared by either step-growth or chain-growth polymerization. Each processing strategy affords distinct advantages in terms of capabilities and resulting properties of the network. This work describes the synthesis, processing, and characterization of cross-linked polyester networks based on Diels-Alder coupling reactions. Hyperbranched furan-modified polyester precursors based on poly(glycerol-co-sebacate) are coupled with bifunctional maleimide cross-linking agents. The chemical and thermomechanical properties of the elastomers are characterized at various stages of network formation. Experimental observations of gel formation are compared to theoretical predictions derived from Flory-Stockmayer relationships. This cross-linking strategy confers unique advantages in processing and properties including the ability to fabricate biodegradable reconfigurable covalent networks without additional catalysts or reaction byproducts. Reconfigurable biodegradable networks using Diels-Alder cycloaddition reactions permit the fabrication of shape-memory polymers with complex permanent geometries. Biodegradable elastomers based on polyester networks with molecular reconfigurability achieve vastly expanded properties and processing capabilities for potential applications in medicine and beyond.