TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.

Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3-CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to-cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.

A macromolecular cross-linked alginate aerogel with excellent concentrating effect for rapid hemostasis.

Alginate-based materials present promising potential for emergency hemostasis due to their excellent properties, such as procoagulant capability, biocompatibility, low immunogenicity, and cost-effectiveness. However, the inherent deficiencies in water solubility and mechanical strength pose a threat to hemostatic efficiency. Here, we innovatively developed a macromolecular cross-linked alginate aerogel based on norbornene- and thiol-functionalized alginates through a combined thiol-ene cross-linking/freeze-drying process. The resulting aerogel features an interconnected macroporous structure with remarkable water-uptake capacity (approximately 9000 % in weight ratio), contributing to efficient blood absorption, while the enhanced mechanical strength of the aerogel ensures stability and durability during the hemostatic process. Comprehensive hemostasis-relevant assays demonstrated that the aerogel possessed outstanding coagulation capability, which is attributed to the synergistic impacts on concentrating effect, platelet enrichment, and intrinsic coagulation pathway. Upon application to in vivo uncontrolled hemorrhage models of tail amputation and hepatic injury, the aerogel demonstrated significantly superior performance compared to commercial alginate hemostatic agent, yielding reductions in clotting time and blood loss of up to 80 % and 85 %, respectively. Collectively, our work illustrated that the alginate porous aerogel overcomes the deficiencies of alginate materials while exhibiting exceptional performance in hemorrhage, rendering it an appealing candidate for rapid hemostasis.

Diselenide-Containing Polymer Based on New Antitumor Mechanism as Efficient GSH Depletion Agent for Ferroptosis Therapy.

Glutathione (GSH) depletion-induced ferroptosis has emerged as a promising treatment for malignant cancer. It works by inactivating glutathione peroxidase 4 (GPX4) and facilitating lipid peroxidation. However, effectively delivering inducers and depleting intracellular GSH remains challenging due to the short half-lives and high hydrophobicity of small-molecule ferroptosis inducers. These inducers often require additional carriers. Herein, diselenide-containing polymers can consume GSH to induce ferroptosis for pancreatic cancer therapy. The diselenide bonds are controllably built into the backbone of the polycarbonate with a targeting peptide CRGD (Cys-Arg-Gly-Asp), which allows for self-assembly into stable nanoparticles (denoted CRNSe) for self-delivery. Significantly, at a concentration of 12 µg mL-1, CRNSe binds to the active site cysteine of GSH resulting in a thorough depletion of GSH. In contrast, the disulfide-containing analog only causes a slight decrease in GSH level. Moreover, the depletion of GSH inactivates GPX4, ultimately inducing ferroptosis due to the accumulation of lipid peroxide in BxPC-3 cells. Both in vitro and in vivo studies have demonstrated that CRNSe exhibits potent tumor suppressive ability with few side effects on normal tissue. This study validates the anti-tumor mechanism of diselenide-containing polymers in addition to apoptosis and also provides a new strategy for inherently inducing ferroptosis in cancer therapy.

An Injectable, Adhesive, and Self-Healing Hydrogel with Inherently Antibacterial Property for Wound Dressing.

Antibacterial hydrogel has emerged as an excellent candidate for wound dressing with the ability to eliminate infection and promote wound healing. Herein, a dynamic hydrogel is developed by Schiff base reaction of mixed charged polypeptides and oxidized dextran (ODex). Specifically, biodegradable polypeptides of 1-(propylthio)acetic acid-3-butylimidazole-modified poly(L-lysine) (PLL-PBIM) and adipate dihydrazide-modified poly(L-glutamic acid) (PLG-ADH) are achieved with tunable substitution and charge. By mixing with ODex, charged polypeptides of PLL-PBIM and PLG-ADH led to an injectable and self-healing hydrogel in seconds. The injectable and self-healing performances of the hydrogels are ascribed to the reversible imine and hydrazone bonds formed between polypeptides and ODex. The positively charged hydrogels exhibited over 95% antibacterial activity against E. coli and S. aureus. An optimized balancing of PLG-ADH and PLL-PBIM significantly reduced the hemolysis rate and cytotoxicity of hydrogels. Therefore, the dynamic hydrogel with excellent biocompatibility and inherently antibacterial ability can have potential application for wound dressing.

Highly resilient and fatigue-resistant poly(4-methyl-ε-caprolactone) porous scaffold fabricated via thiol-yne photo-crosslinking/salt-templating for soft tissue regeneration.

Elastomeric scaffolds, individually customized to mimic the structural and mechanical properties of natural tissues have been used for tissue regeneration. In this regard, polyester elastic scaffolds with tunable mechanical properties and exceptional biological properties have been reported to provide mechanical support and structural integrity for tissue repair. Herein, poly(4-methyl-ε-caprolactone) (PMCL) was first double-terminated by alkynylation (PMCL-DY) as a liquid precursor at room temperature. Subsequently, three-dimensional porous scaffolds with custom shapes were fabricated from PMCL-DY via thiol-yne photocrosslinking using a practical salt template method. By manipulating the Mn of the precursor, the modulus of compression of the scaffold was easily adjusted. As evidenced by the complete recovery from 90% compression, the rapid recovery rate of >500 mm min-1, the extremely low energy loss coefficient of <0.1, and the superior fatigue resistance, the PMCL20-DY porous scaffold was confirmed to harbor excellent elastic properties. In addition, the high resilience of the scaffold was confirmed to endow it with a minimally invasive application potential. In vitro testing revealed that the 3D porous scaffold was biocompatible with rat bone marrow stromal cells (BMSCs), inducing BMSCs to differentiate into chondrogenic cells. In addition, the elastic porous scaffold demonstrated good regenerative efficiency in a 12-week rabbit cartilage defect model. Thus, the novel polyester scaffold with adaptable mechanical properties may have extensive applications in soft tissue regeneration.

A biodegradable, flexible photonic patch for in vivo phototherapy.

Diagnostic and therapeutic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, we present a flexible, biodegradable photonic device called iCarP with a micrometer scale air gap between a refractive polyester patch and the embedded removable tapered optical fiber. ICarP combines the advantages of light diffraction by the tapered optical fiber, dual refractions in the air gap, and reflection inside the patch to obtain a bulb-like illumination, guiding light towards target tissue. We show that iCarP achieves large area, high intensity, wide spectrum, continuous or pulsatile, deeply penetrating illumination without puncturing the target tissues and demonstrate that it supports phototherapies with different photosensitizers. We find that the photonic device is compatible with thoracoscopy-based minimally invasive implantation onto beating hearts. These initial results show that iCarP could be a safe, precise and widely applicable device suitable for internal organs and tissue illumination and associated diagnosis and therapy.

Hypothermia-Triggered Mesoporous Silica Particles for Controlled Release of Hydrogen Sulfide to Reduce the I/R Injury of the Myocardium.

Despite the fact that heart transplantation (HTx) is a relatively mature procedure, heart ischemic and reperfusion (I/R) injury during HTx remains a challenge. Even after a successful operation, the heart will be at risk of primary graft failure and mortality during the first year. In this study, temperature-sensitive polymer poly(N-n-propylacrylamide-co-N-tert-butyl acrylamide) (PNNTBA) was coated on diallyl trisulfide (DATS)-loaded mesoporous silica nanoparticles (DATS-MSN) to synthesize hypothermia-triggered hydrogen sulfide (H2S) releasing particles (HT-MSN). Because the PNNTBA shell dissolves in phosphate-buffered saline at 4 °C, the loaded DATS could continuously release H2S within 6 h when activated by glutathione (GSH). Furthermore, after co-culturing biocompatible HT-MSN with cardiomyocytes, H2S released from HT-MSN at 4 °C was found to protect cardiomyocytes from ischemic and reperfusion (I/R) injury. In detail, the rate of cell apoptosis and lactate dehydrogenase activity was decreased, as manifested by increased BCL-2 expression and decreased BAX expression. More importantly, in an isolated heart preservation experiment, HT-MSN demonstrated potent protection against cardiac I/R injury and reduced expression of inflammatory factors TNF-α and IL-1ß. This study provided a new method for the controlled release of H2S by the donor and myocardial protection from I/R injury.

Preparation of AIE Functional Single-Chain Polymer Nanoparticles and Their Application in H2 O2 Detection through Intermolecular Heavy-Atom Effect.

Single-chain polymer nanoparticles (SCNPs) are soft matter constructed by intrachain crosslinks, with promising prospects in detection and catalysis. Herein, a fluorescent core (SCNPs) with aggregation-induced emission (AIE) is prepared, applying for H2 O2 detection through intermolecular heavy-atom effect. In detail, the SCNPs precursors are synthesized by ring-opening copolymerization. Then the SCNPs are prepared by intramolecularly cross-linking via olefin metathesis. Imitating the structure of AIE dots, SCNPs are encapsulated by H2 O2 -responsive polymers. Probably due to the stable secondary structure of SCNPs, the obtained micelles show stable fluorescence performance. Furthermore, as the heavy-atom, tellurium is introduced into the carriers to construct the heavy-atom effect. In this micelle-based system, the SCNPs act as the fluorescent core, and the stimuli-responsive polymer acts as the carrier and the fluorescent switch. The hydrophilicity of the tellurium-containing segment is affected by the concentration of H2 O2 , resulting in a change in the distance from the SCNPs, which ultimately leads to a change in the fluorescence intensity. Furthermore, tellurium is particularly sensitive to H2 O2 , which can detect low concentrations of H2 O2 . The SCNPs are merged with AIE materials, with the hope of exploring new probe designs.

Antibacterial, antioxidant and anti-inflammatory PLCL/gelatin nanofiber membranes to promote wound healing.

Epigallocatechin-3-O-gallate (EGCG) is a green biomedical agent for promoting wound healing, which possess excellent antibacterial, antioxidant and anti-inflammatory activities. For improving the low bioavailability challenges of EGCG in vivo, we had successful created a low-cost and simple wound dressing Poly (L-Lactic-co-caprolactone) (PLCL)/Gelatin/EGCG/Core-shell nanofiber membrane (PGEC) with drug sustained release capacity through coaxial electrospinning technology. In vitro experimental indicated that the core-shell structure wound dressing had excellent biocompatibility, antibacterial and antioxidant ability, which could support cell viability and proliferation, encourage re-epithelialization during the healing process, inhibit subsequent wound infection and thus promote wound regeneration. In vivo experimental demonstrated that PGEC wound dressing could promote wound healing, the histological results further demonstrated that PGEC not only facilitated early wound closure but also influenced cellular differentiation and tissue organization. Meanwhile, PGEC had excellent hemostatic ability. Taken all together, we believed that the PGEC wound dressing, which could localize delivery of EGCG, had high potential clinical application for promoting wound healing, hemostasis or other related clinical applications in the future.

A multifunctional green antibacterial rapid hemostasis composite wound dressing for wound healing.

Rapid hemostasis and antibacterial properties are essential for novel wound dressings to promote wound healing. In particular, timely and rapid hemostasis could be of benefit to reduce the mortality caused by excessive bleeding loss. Herein, we present a novel strategy of combining electrospinning technology with post-modification technology to prepare a multifunctional wound dressing, cellulose diacetate-based composite wound dressing (CDCE), with rapid hemostasis and antibacterial activity. It is interesting that the CDCE wound dressing had superhydrophilicity, high water absorption, and strong absorbing capacity, which could eliminate the exudate around the wound in a timely manner and further promote rapid hemostasis. Additionally, its excellent antibacterial properties could inhibit severe infection in the wound and accelerate wound healing. Based on these advantages, the novel CDCE wound dressing could promote wound contraction and further accelerate wound healing compared with the common traditional wound dressing gauze. Taken together, the multifunctional CDCE wound dressing has high potential for clinical application in the future.

Synthetic Mimics of Antimicrobial Peptides for the Targeted Therapy of Multidrug-Resistant Bacterial Infection.

Antibacterial materials are highly demanded in treatment of bacterial infection, especially severe ones with multidrug-resistance. Herein, pH-responsive polypeptide, i.e., poly-L-lysine modified by 1-(propylthio)acetic acid-3-octylimidazolium and citraconic anhydride (PLL-POIM-CA), is synthesized by post-polymerization modification of poly-L-lysine (PLL) with 1-(propylthio)acetic acid-3-octylimidazolium (POIM) and citraconic anhydride (CA). It is observed that PLL-POIM-CA is stable under normal physiological condition, while CA cleaves rapidly at weakly acidic environment like bacterial infectious sites. The hydrolyzed PLL-POIM-CA exhibits excellent broad-spectrum antibacterial activities against Gram-negative bacteria of Escherichia coli and Gram-positive bacteria of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). In particular, the minimum inhibitory concentration (MIC) against multidrug-resistant bacteria like MRSA is as low as 7.8 µg mL-1 . Moreover, PLL-POIM-CA exhibits good biocompatibility with mouse fibroblast cells (L929) in vitro and improved hemocompatibility with an HC50 exceeding 5000 µg mL-1 . Therefore, PLL-POIM-CA displays an excellent bacteria versus cells selectivity (HC50 /MIC) over 534, which is 53 times higher than natural antimicrobial peptide of indolicidin. It is further demonstrated in vivo that the antimicrobial polypeptide effectively accelerates MRSA-infected wound healing by relieving local inflammatory response. Therefore, this targeted antimicrobial polypeptide has broad application prospects for the treatment of multidrug-resistant bacterial infection.

Antibacterial AIE polycarbonates endowed with selective imaging capabilities by adjusting the electrostaticity of the mixed-charge backbone.

Combining rapid microbial discrimination with antibacterial properties, multi-functional biomacromolecules allow the timely diagnosis and effective treatment of infectious diseases. Through a two-step approach involving organocatalytic ring-opening copolymerization and thiol-ene modification, aggregation-induced emission (AIE) polycarbonates decorated with tertiary amines were prepared. After being ionized using acetic acid, the obtained cationic AIE polycarbonate with excellent water solubility showed bacteria imaging capabilities and antibacterial activities toward both Gram-positive S. aureus and Gram-negative E. coli. It was indicated via scanning electron microscope images that the bactericidal mechanism involved membrane lysis, consistent with most cationic polymers. Through further co-grafting carboxyl and tertiary amine groups, mixed-charge AIE polycarbonates were obtained. The isoelectric points of such mixed-charge AIE polycarbonates could be simply tuned based on the grafting ratio of positive and negative moieties. Compared with the cationic AIE polycarbonate, mixed-charge AIE polycarbonates allowed the rapid and selective imaging of S. aureus, but not E. coli. The selectivity probably arose from the lower binding forces between the mixed-charge AIE polycarbonates and the low-negative-charge components of the E. coli surface. Therefore, these biodegradable polycarbonates, which integrated selective bacteria imaging and antibiotic abilities, potentially suggest a precision medicine approach for infectious diseases. The overall synthesis approach and mixed-charge AIE polycarbonates provide new references for the design and application of bio-related AIE polymers.

Sequential Release of Small Extracellular Vesicles from Bilayered Thiolated Alginate/Polyethylene Glycol Diacrylate Hydrogels for Scarless Wound Healing.

Excessive scar formation has adverse physiological and psychological effects on patients; therefore, a therapeutic strategy for rapid wound healing and reduced scar formation is urgently needed. Herein, bilayered thiolated alginate/PEG diacrylate (BSSPD) hydrogels were fabricated for sequential release of small extracellular vesicles (sEVs), which acted in different wound healing phases, to achieve rapid and scarless wound healing. The sEVs secreted by bone marrow derived mesenchymal stem cells (B-sEVs) were released from the lower layer of the hydrogels to promote angiogenesis and collagen deposition by accelerating fibroblast and endothelial cell proliferation and migration during the early inflammation and proliferation phases, while sEVs secreted by miR-29b-3p-enriched bone marrow derived mesenchymal stem cells were released from the upper layer of the hydrogels and suppressed excessive capillary proliferation and collagen deposition during the late proliferation and maturation phases. In a full-thickness skin defect model of rats and rabbit ears, the wound repair rate, angiogenesis, and collagen deposition were evaluated at different time points after treatment with BSSPD loaded with B-sEVs. Interestingly, during the end of the maturation phase in the in vivo model, tissues in the groups treated with BSSPD loaded with sEVs for sequential release (SR-sEVs@BSSPD) exhibited a more uniform vascular structure distribution, more regular collagen arrangement, and lower volume of hyperplastic scar tissue than tissues in the other groups. Hence, SR-sEVs@BSSPD based on skin repair phases was successfully designed and has considerable potential as a cell-free therapy for scarless wound healing.

A Drug-Free Therapeutic System for Cancer Therapy by Diselenide-Based Polymers Themselves.

The application of nanotechnology-based drug delivery systems has resulted in great progresses in cancer therapy. However, current systems ultimately depend on the action of the drug itself and almost all nanocarriers only serve as excipients without any therapeutic efficacy. Herein, a drug-free therapeutic system is put forward, in which synthetic polymers themselves naturally exhibit effective anticancer activity without the loading of additional chemotherapy drugs. Aiming at this goal, amphiphilic poly(diselenide-carbonate) copolymers (PSeSeTMC), consisting of monomethyl ether poly(ethylene glycol) and diselenide-based polycarbonates, are designed and synthesized to build spherical nanoparticles, which show effective and broad-spectrum anticancer activities against multiple cancer cell lines and high selectivity toward cancer cells. Moreover, the anticancer activities can be well controlled by tuning the selenium contents in polymers. Mechanistic investigations indicate that PSeSeTMC can selectively induce cancer cells to express excessive reactive oxygen species, thereby leading to significant cellular apoptosis. In vivo antitumor studies further demonstrate high therapeutic efficacy and low side effects on normal tissue. Overall, this work provides a novel approach for cancer therapy by utilizing carriers themselves. Considering the fabrication process is pretty simple, this diselenide-based polymeric system has great potential in clinical translation.

Fabrication and evaluation of modified poly(ethylene terephthalate) microfibrous scaffolds for hepatocyte growth and functionality maintenance.

For hepatocyte culture in vitro, the surface feature of utilized scaffolds exerts a direct impact on cell adhesion, growth and differentiated functionality. Herein, to regulate hepatocyte growth and differentiated functionality, modified microfibrous scaffolds were fabricated by surface grafting monoamine terminated lactobionic lactone (L-NH2) and gelatin onto non-woven poly(ethylene terephthalate) (PET) fibrous substrate (PET-Gal and PET-Gel), respectively. The physicochemical properties of PET scaffolds before and after modification were characterized. Upon 15-day culture, the effects of modified PET scaffolds on growth and differentiated functionality of human induced hepatocytes (hiHeps) were evaluated, compared with that of control without modification. Results demonstrated that both L-NH2 and gelatin modifications improved scaffold properties including hydrophilicity, water uptake ratio, stiffness and roughness, resulting in efficient cell adhesion, ~20-fold cell expansion and enhanced differentiated functionality. After culture for 15 days, PET-Gal cultured cells formed aggregates, displaying better cell viability and significantly higher differentiated functionality regarding albumin secretion, urea synthesis, phases I (cytochrome P450, CYP1A1/2 and CYP3A4) and II (uridine 5'-diphosphate glucuronosyltransferases, UGT) enzyme activity, biliary excretion and detoxification ability (ammonia elimination and bilirubin conjugation), compared with PET and PET-Gel cultured ones. Hence, as a three-dimensional (3D) microfibrous scaffold, PET-Gal promotes hiHeps growth and differentiated functionality maintenance, which is promisingly utilized in bioartificial liver (BAL) bioreactors.

Dual stimuli-responsive polypeptide prepared by thiol-ene click reaction of poly(l-cysteine) and N, N-dimethylaminoethyl acrylate.

Stimuli-responsive polymers that can undergo conformational changes with external triggers have enabled themselves as smart materials for various utilizations, among which biodegradability is of particular importance to be engineered for biomedical application. In this study, a thermo and pH dual responsive polypeptide (N, N-dimethylaminoethyl acrylate-modified poly(l-cysteine)) (PLC-g-DMAEA) was prepared by the combination of N-carboxyanhydride ring-open polymerization and thiol-ene click chemistry. The biodegradable poly(l-cysteine) (PLC) with pendant thiol groups provided an easily clickable backbone for postmodification, which was demonstrated by reacting with a well-known monomer of N, N-dimethylaminoethyl acrylate (DMAEA) to achieve both temperature and pH responsiveness. The irreversible thermo-response of PLC-g-DMAEA could be attributed to the ordered ß-sheets formed upon heating, leading to the trapped side groups with poor water accessibility. Moreover, this copolymer precipitated at pH ranging from 7.5 to 9.7, but protonation of tertiary amine groups (pH < 7.5) and salt forming of masked thiol groups (pH > 9.7) rendered it soluble in water. Our results revealed that a ready available vinyl monomer could be easily clicked onto the biodegradable PLC and its stimuli responsiveness would be reserved. Moreover, the primary and secondary structures of PLC might influence the conformation, thus leading to the unique responsive behavior of the resulted copolymer.

In Situ Forming and Reversibly Cross-Linkable Hydrogels Based on Copolypept(o)ides and Polysaccharides.

The emerging tide of hydrogels in biomedical fields drives them to possess good biocompatibility, tunable mechanical properties, and fast gelation process. Herein, a composite hydrogel containing copolypept(o)ides and functional polysaccharides was constructed through dynamic acylhydrazone linkages. First, a series of peptide-peptoid copolymers were synthesized by ring-opening polymerization of sarcosine (Sar) and l-glutamic acid γ-benzyl ester (BLG) N-carboxyanhydrides (NCAs). The benzyl groups of BLG units were substituted with hydrazide groups through ester-amide exchange aminolysis reaction. The statistical copolymer of poly(sarcosine-co-glutamate-hydrazide) (P(Sar-co-GH)) was chosen as an optimized precursor due to its excellent water solubility and gel-forming ability with aldehyde-modified sodium alginate (OSA). Moreover, cellulose nanocrystals (CNCs) were prepared as nanofillers to reinforce the P(Sar-co-GH)-OSA hydrogel. We demonstrated that the copolymer sequences and composition contents made a difference to the properties of the formed hydrogels by variation of the cross-linking density. The dynamic acylhydrazone bonds endowed hydrogels with pH responsiveness and reversible networks. The NIH/3T3 cells encapsulated in the hydrogels maintained high viability and proliferation abilities, indicating that the nanocomposite hydrogels could be explored to fabricate a customized responsive drug delivery system or cell scaffolds for tissue engineering.

Hepatocyte culture on 3D porous scaffolds of PCL/PMCL.

The development of three-dimensional (3D) porous scaffolds for soft tissue engineering mainly focused on manipulation of scaffold properties with cell behaviors. By emulsion freeze-drying method, four types of porous scaffolds were prepared from amorphous poly(4-methy-ε-caprolactone) (PMCL) and semi-crystalline poly(ε-caprolactone) (PCL) at different weight ratios, named as PMCL0, PMCL30, PMCL50 and PMCL70, respectively. Visual observation on cross-sectional images of the scaffolds appeared as sponge-like materials with three-dimensional and highly porous morphologies. However, the pore size, porosity and wettability of blends were not decreased linearly with increasing amorphous PMCL. Distinguished from PMCL30 or PMCL70, PMCL50 preserved intact PCL crystals distributed in amorphous matrix, resulting in the lowest Young's modulus (E) and relatively high wettability. From in vitro cell culture, it was observed that PMCL50 scaffold supported human induced hepatocytes (hiHeps) proliferation and function preservation best among all scaffolds. hiHeps on PMCL50 inclined to adopt fibroblastic morphology, whereas formed spheroidal morphology on PMCL0. It was suggested that our bare scaffolds with tailored properties have shown remarkable capability towards hiHep proliferation and function expression.

Chemo-Enzymatic Synthesis of Poly(4-piperidine lactone- b-ω-pentadecalactone) Block Copolymers as Biomaterials with Antibacterial Properties.

With increasing troubles in bacterial contamination and antibiotic-resistance, new materials possessing both biocompatibility and antimicrobial efficacy are supposed to be developed for future biomedical application. Herein, we demonstrated a chemo-enzymatic ring opening polymerization (ROP) approach for block copolyester, that is, poly(4-benzyl formate piperidine lactone- b-ω-pentadecalactone) (PNPIL- b-PPDL), in a one-pot two-step process. Afterward, cationic poly(4-piperidine lactone- b-ω-pentadecalactone) (PPIL- b-PPDL) with pendent secondary amino groups was obtained via acidic hydrolysis of PNPIL- b-PPDL. The resulting cationic block copolyester exhibited high antibacterial activity against Gram negative E. coli and Gram positive S. aureus, while showed low toxicity toward NIH-3T3 cells. Moreover, the antibacterial property, cytotoxicity and degradation behavior could be tuned simply by variation of PPIL content. Therefore, we anticipate that such cationic block copolymers could potentially be applied as biomaterials for medicine or implants.