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1.
ACS Appl Mater Interfaces ; 16(14): 17323-17338, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38556990

RESUMO

Electroactive hydrogels have garnered extensive interest as a promising approach to myocardial tissue engineering. However, the challenges of spatiotemporal-specific modulation of individual pathological processes and achieving nontoxic bioresorption still remain. Herein, inspired by the entire postinfarct pathological processes, an injectable conductive bioresorbable black phosphorus nanosheets (BPNSs)-loaded hydrogel (BHGD) was developed via reactive oxide species (ROS)-sensitive disulfide-bridge and photomediated cross-linking reaction. Significantly, the chronologically programmed BHGD hydrogel can achieve graded modulation during the inflammatory, proliferative, and maturation phases of myocardial infarction (MI). More details, during early infarction, the BHGD hydrogel can effectively reduce ROS levels in the MI area, inhibit cellular oxidative stress damage, and promote macrophage M2 polarization, creating a favorable environment for damaged myocardium repair. Meanwhile, the ROS-responsive structure can protect BPNSs from degradation and maintain good conductivity under MI microenvironments. Therefore, the BHGD hydrogel possesses tissue-matched modulus and conductivity in the MI area, facilitating cardiomyocyte maturation and electrical signal exchange, compensating for impaired electrical signaling, and promoting vascularization in infarcted areas in the maturation phase. More importantly, all components of the hydrogel degrade into nontoxic substances without adverse effects on vital organs. Overall, the presented BPNS-loaded hydrogel offers an expandable and safe option for clinical treatment of MI.


Assuntos
Hidrogéis , Infarto do Miocárdio , Humanos , Hidrogéis/química , Espécies Reativas de Oxigênio , Infarto do Miocárdio/terapia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo
3.
ACS Nano ; 18(11): 8168-8179, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38437515

RESUMO

Advancements in cell coculture systems with porous membranes have facilitated the simulation of human-like in vitro microenvironments for diverse biomedical applications. However, conventional Transwell membranes face limitations in low porosity (ca. 6%) and optical opacity due to their large thickness (ca. 10 µm). In this study, we demonstrated a one-step, large-scale fabrication of freestanding polymer ultrathin porous (PUP) membranes with thicknesses of hundreds of nanometers. PUP membranes were produced by using a gap-controlled bar-coating process combined with polymer blend phase separation. They are 20 times thinner than Transwell membranes, possessing 3-fold higher porosity and exhibiting high transparency. These membranes demonstrate outstanding molecular permeability and significantly reduce the cell-cell distance, thereby facilitating efficient signal exchange pathways between cells. This research enables the establishment of a cutting-edge in vitro cell coculture system, enhancing optical transparency, and streamlining the large-scale manufacturing of porous membranes.


Assuntos
Membranas Artificiais , Polímeros , Humanos , Técnicas de Cocultura , Porosidade
4.
Adv Healthc Mater ; 13(10): e2303574, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38115543

RESUMO

Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro-wound healing properties of existing anti-adhesion barriers, this work reports an injectable adhesive-antifouling bifunctional hydrogel (AAB-hydrogel). This AAB-hydrogel can be constructed by "two-step" injection. The tissue adhesive hydrogel based on gallic acid-modified chitosan and aldehyde-modified dextran is prepared as the bottom hydrogel (B-hydrogel) by Schiff base reaction. The aldehyde-modified zwitterionic dextran/carboxymethyl chitosan-based hydrogel is formed on the B-hydrogel surface as the antifouling top hydrogel (T-hydrogel). The AAB-hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti-adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion-cecum defect model. Results suggest that the AAB-hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB-hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB-hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.


Assuntos
Incrustação Biológica , Quitosana , Adesivos Teciduais , Camundongos , Animais , Hidrogéis/farmacologia , Hidrogéis/química , Quitosana/farmacologia , Quitosana/química , Adesivos , Adesivos Teciduais/química , Dextranos/farmacologia , Aderências Teciduais/prevenção & controle , Aderências Teciduais/metabolismo , Modelos Animais de Doenças , Aldeídos , Antibacterianos/química
5.
J Mater Chem B ; 11(45): 10845-10858, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37937417

RESUMO

Healing large-scale wounds has been a long-standing challenge in the field of biomedicine. Herein, we propose an injectable oxidated sodium alginate/gelatin/3,3'-dithiobis(propionic hydrazide)-aurum (Alg-CHO/gelatin/DTPH-Au) hydrogel filler with asymmetric adhesion ability and removability, which is formed by the Schiff-base reaction between aldehyde-based sodium alginate and multi-amino crosslinkers (gelatin and DTPH), combined with the coordination interaction between Au nanoparticles and disulfide bond of DTPH. Consequently, the prepared Alg-CHO/gelatin/DTPH-Au hydrogel exhibits high mechanical properties and injectable behaviors owing to its multiple-crosslinked interactions. Moreover, because various types of interaction bonding form on the contact side with the tissue, denser crosslinking of the upper layer relative to the lower layer occurs. Combined with the temperature difference between the upper and lower surfaces, this results in asymmetric adhesive properties. Owing to the photothermal effect, the reversible coordination interaction between Au nanoparticles and DTPH and the change in the triple helix structure of gelatin to a coil structure impart the filler-phased removability and antibacterial ability. The choice of all natural polymers also allows for favorable degradability of the wound filler and outstanding biocompatibility. Based on these features, this versatile wound filler can achieve a wide range of applications in the field of all-skin wound repair.


Assuntos
Hidrogéis , Nanopartículas Metálicas , Hidrogéis/química , Adesivos , Gelatina/química , Ouro , Cicatrização , Alginatos/química
6.
Nat Commun ; 14(1): 6226, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37803005

RESUMO

With advances in tissue engineering and bioelectronics, flexible electronic hydrogels that allow conformal tissue integration, online precision diagnosis, and simultaneous tissue regeneration are expected to be the next-generation platform for the treatment of myocardial infarction. Here, we report a functionalized polyaniline-based chronological adhesive hydrogel patch (CAHP) that achieves spatiotemporally selective and conformal embedded integration with a moist and dynamic epicardium surface. Significantly, CAHP has high adhesion toughness, rapid self-healing ability, and enhanced electrochemical performance, facilitating sensitive sensing of cardiac mechanophysiology-mediated microdeformations and simultaneous improvement of myocardial fibrosis-induced electrophysiology. As a result, the flexible CAHP platform monitors diastolic-systolic amplitude and rhythm in the infarcted myocardium online while effectively inhibiting ventricular remodeling, promoting vascular regeneration, and improving electrophysiological function through electrocoupling therapy. Therefore, this diagnostic and therapeutic integration provides a promising monitorable treatment protocol for cardiac disease.


Assuntos
Adesivos , Infarto do Miocárdio , Humanos , Adesivos/farmacologia , Coração , Miocárdio , Infarto do Miocárdio/terapia , Remodelação Ventricular , Hidrogéis/uso terapêutico , Hidrogéis/farmacologia
7.
Adv Healthc Mater ; 12(30): e2301696, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37669499

RESUMO

Postoperative peritoneal adhesion is a serious clinical complication. Various hydrogel barriers have been developed to prevent peritoneal adhesion. However, it remains a challenge to design a hydrogel with desirable physicochemical properties and bioactivities. In this study, a zwitterionic polysaccharide-based multifunctional hydrogel is developed using epigallocatechin-3-gallate (EGCG) to prevent postoperative abdominal adhesion. This hydrogel is simple to use and has desirable properties, such as excellent injectability, self-healing, and non-swelling properties. The hydrogel also has ultralow fouling capabilities, such as superior bactericidal performance, cell and protein adhesion, and low immunogenicity resistance. Moreover, the hydrogel exhibits good antioxidant activity, which is attributed to the integration of EGCG. Furthermore, the detailed mechanism from in vivo and in vitro experimental studies illustrates that hydrogel compositions can synergistically prevent adhesion formation through multiple pathways, including anti-inflammatory and antioxidant capabilities and inhibition effects on the mesothelial-mesenchymal transition (MMT) process induced by transforming growth factor (TGF-ß). In summary, this zwitterionic multifunctional hydrogel has great potential to prevent postoperative adhesion formation in the clinical setting.


Assuntos
Hidrogéis , Peritônio , Hidrogéis/química , Peritônio/metabolismo , Peritônio/cirurgia
8.
Acta Biomater ; 166: 201-211, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37150278

RESUMO

Hydrogels show eminent advantages in biomedical and pharmaceutical fields. However, their application as coating materials for biomedical devices is limited by several key challenges, such as lack of universality, weak mechanical strength, and low adhesion to the substrate. Here we report versatile and tough adhesion composite hydrogel paints (CHPs), which consist of zwitterionic copolymers and microgels, both with reactive groups. The CHPs exhibit tunable rheology and thickness, hydrophilicity, biofouling resistance, durability, and convenient fabrication on metal, polymer, and inorganic surfaces with arbitrary shapes. As a proof-of-concept, the CHP-surgical sutures demonstrate exceptional lubrication, drug delivery, anti-infection, and anti-fibrous capsule properties. Moreover, the CHP-PVC tubing effectively prevents thrombus formation in vitro and ex vivo rabbit blood circulation without anticoagulants. This work provides valuable insights for enhancing and developing integrated hydrogel technologies for biomedical devices. STATEMENT OF SIGNIFICANCE: The combination of hydrogel and biomedical devices can enable numerous existing applications in medicine. In this study, inspired by the principle of microgel reinforcement in industrial paints, we propose a simple and versatile zwitterionic composite hydrogel paints (CHPs) strategy, which can be easily applied to diverse substrates with arbitrary shapes by covalent grafting between complementary groups by brush, dip, or spray. The CHPs integrated universality, tough adhesion, mechanical durability, and anti-biofouling properties because of their unique chemical composition and coating structure design. This strategy provides a simple and versatile route for surface modification of biomedical devices.


Assuntos
Incrustação Biológica , Microgéis , Animais , Coelhos , Hidrogéis/farmacologia , Hidrogéis/química , Adesivos , Polímeros/química , Incrustação Biológica/prevenção & controle
9.
J Mater Chem B ; 11(11): 2504-2517, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36852742

RESUMO

The preservation of cells at cryogenic temperatures requires the presence of cryoprotectants (CPAs). Dimethyl sulfoxide (DMSO), as a state-of-the-art CPA, is widely used for the storage of many types of cells. However, its intrinsic toxicity is still an obstacle for its applications in clinical practice. Herein, we report a DMSO analogue, L-methionine sulfoxide (Met(O)-OH), as a CPA for cell cryopreservation. The molecular-level cryopreservation roles of Met(O)-OH were investigated by experiments and molecular dynamics simulations. The results also found that Met(O)-OH showed high ice recrystallization inhibition (IRI) activity and the ice crystals in Met(O)-OH solution tend to be relatively round and smooth; moreover, the ice size was significantly reduced to 30.26 µm compared with pure water (135.87 µm) or DMSO solution (45.08 µm). At the molecular level, Met(O)-OH could stably bind the surface of the ice crystals and form more stable hydrogen bonds with ice compared with L-methionine. Moreover, Met(O)-OH could significantly reduce the damage to cells caused by osmotic shock and did not change the cell viability even at high concentration (4%). Based on these results, nucleated L929 cells and anuclear sheep red blood cells (SRBCs) were used as cell models to investigate the cryopreservation activity of Met(O)-OH. The results suggested that, under the optimum protocol, Met(O)-OH showed an effective post-thaw survival efficiency with ultrarapid freezing, and the post-thaw survival efficiency of L929 cells reached 84.0%. This work opens up the possibility for an alternative to traditional toxic CPA DMSO, and provides insights for the development of DMSO analogues with non-toxic/low toxicity for cell cryoprotection applications.


Assuntos
Aminoácidos , Crioprotetores , Dimetil Sulfóxido , Gelo , Animais , Aminoácidos/farmacologia , Crioprotetores/farmacologia , Crioprotetores/química , Dimetil Sulfóxido/química , Dimetil Sulfóxido/farmacologia , Congelamento , Ovinos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia
10.
Int J Biol Macromol ; 232: 123449, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-36709811

RESUMO

In order to improve the hemostatic effect of the hemostatic dressing for non-compressible wounds, unknown bleeding points and irregularly shaped wounds, a self-gelling hemostasis powder based on polyacrylic acid/polyacrylamide/quaternate chitosan (PAA/PAM/QCS) is prepared in this study. When in contact with water, the PAA/PAM/QCS can fuse and rapidly form a stable hydrogel in a short time (< 0.25 min). The PAA/PAM ratio is the main parameter that modulates the formation of the self-gel. The PAA/PAM self-gel can be formed only when the PAA/PAM ratio is 5:5, and the introduction of QCS does not influence the self-gelling behaviors and hydrogel stability. Moreover, the PAA/PAM/QCS self-gel shows good adhesive properties on wet tissue surfaces. In addition, the introduction of QCS improves the antibacterial activity of the self-gelling hemostasis powder. Furthermore, the prepared PAA/PAM/QCS powder can rapidly adsorb lots of blood, aggregate blood cells and platelets. The hemostatic results in vivo show that PAA/PAM/QCS powder is superior to the control group and commercial product groups (chitosan powder) with performance similar to hemostatic zeolite in terms of the amount of bleeding and hemostatic time. Therefore, the PAA/PAM/QCS self-gelling powder shows great application prospects for rapid hemostasis.


Assuntos
Quitosana , Hemostáticos , Humanos , Quitosana/farmacologia , Pós , Hemostáticos/farmacologia , Hemostasia , Hidrogéis/farmacologia , Hemorragia/tratamento farmacológico , Antibacterianos/farmacologia
11.
Adv Healthc Mater ; 12(7): e2202309, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36447378

RESUMO

Stem cell therapy integrated with hydrogels has shown promising potential in wound healing. However, the existing hydrogels usually cannot reach the desired therapeutic efficacy for burn wounds due to the inadaptability to wound shape and weak anti-infection ability. Moreover, it is difficult to improve the environment for the survival and function of stem cells under complicated wound microenvironments. In this study, an injectable and self-healing hydrogel (DSC), comprising sulfobetaine-derived dextran and carboxymethyl chitosan, is fabricated through a Schiff-base reaction. Meanwhile, the DSC hydrogel shows high nonfouling properties, including resistance to bacteria and nonspecific proteins; moreover, the prepared hydrogel can provide a biomimetic microenvironment for cell proliferation whilst maintaining the stemness of adipose-derived stem cells (ADSCs) regardless of complex microenvironments. In burnt murine animal models, the ADSCs-laden hydrogel can significantly accelerate wound healing rate and scarless skin tissue regeneration through multiple pathways. Specifically, the ADSCs-laden DSC hydrogel can avoid immune system recognition and activation and thus reduce the inflammatory response. Moreover, the ADSCs-laden DSC hydrogel can promote collagen deposition, angiogenesis, and enhance macrophage M2 polarization in the wound area. In summary, sulfobetaine-derived polysaccharide hydrogel can serve as a versatile platform for stem cell delivery to promote burn wound healing.


Assuntos
Queimaduras , Quitosana , Células-Tronco , Animais , Camundongos , Bandagens , Queimaduras/tratamento farmacológico , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Células-Tronco/citologia , Cicatrização
12.
Langmuir ; 38(46): 14097-14108, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36342971

RESUMO

Ice recrystallization inhibitors inspired from antifreeze proteins (AFPs) are receiving increasing interest for cryobiology and other extreme environment applications. Here, we present a modular strategy to develop polysaccharide-derived biomimetics, and detailed studies were performed in the case of dextran. Poly(vinyl alcohol) (PVA) which has been termed as one of the most potent biomimetics of AFPs was grafted onto dextran via thiol-ene click chemistry (Dex-g-PVA). This demonstrated that Dex-g-PVA is effective in IRI and its activity increases with the degree of polymerization (DP) (sizes of ice crystals were 18.846 ± 1.759 and 9.700 ± 1.920 µm with DPs of 30 and 80, respectively) and fraction of PVA. By means of the dynamic ice shaping (DIS) assay, Dex-g-PVA is found to engage on the ice crystal surfaces, thus the ice affinity accounts for their IRI activity. In addition, Dex- g-PVA displayed enhanced IRI activity compared to that of equivalent PVA alone. We speculate that the hydrophilic nature of dextran would derive PVA in a stretch conformation that favors ice binding. The modular design can not only offer polysaccharides IRI activity but also favor the ice-binding behavior of PVA.


Assuntos
Dextranos , Gelo , Polímeros/química , Cristalização , Proteínas Anticongelantes/química , Polissacarídeos
13.
Mater Today Bio ; 17: 100477, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36388455

RESUMO

As an alternative and a straightforward cryopreservation biotechnological tool, liquid marble provides a promising cryopreservation approach. Currently, effective cell preservation mainly based on the addition of dimethyl sulfoxide (DMSO) and fetal bovine serum (FBS). As state-of-the-art cryoprotectant (CPA), DMSO, has intrinsic toxicity, which is the bottleneck of its widespread application. The complex compositions of FBS have the potential risks of pathogenic microorganism contamination. However, efficient cell cryopreservation using liquid marbles, a platform independent of DMSO and FBS, has not been well investigated yet. Herein, we explore the cryoprotection role of liquid marbles based on gelatin solution. Gelatin has a superior biocompatibility, which DMSO is incomparable. During a freeze-thaw cycle, gelatin produces negligible osmotic pressure, and has high ice recrystallization inhibition (IRI) activity to induce the formation of smaller and smooth ice crystals. Moreover, the specific structure of liquid marble also provides favorable supports for cell survival. The cryopreservation efficiency of mouse fibroblasts cells L929 via the gelatin-based liquid marble was as high as 90%, and the recovered cells could maintain their normal functionalities. This work opens a new window of opportunity for non-toxic and efficient cryopreservation of liquid marbles without the need of DMSO and FBS addition.

14.
ACS Nano ; 16(10): 16234-16248, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36190461

RESUMO

Although hydrogel-based patches have shown promising therapeutic efficacy in myocardial infarction (MI), synergistic mechanical, electrical, and biological cues are required to restore cardiac electrical conduction and diastolic-systolic function. Here, an injectable mechanical-electrical coupling hydrogel patch (MEHP) is developed via dynamic covalent/noncovalent cross-linking, appropriate for cell encapsulation and minimally invasive implantation into the pericardial cavity. Pericardial fixation and hydrogel self-adhesiveness properties enable the MEHP to highly compliant interfacial coupling with cyclically deformed myocardium. The self-adaptive MEHP inhibits ventricular dilation while assisting cardiac pulsatile function. The MEHP with the electrical conductivity and sensitivity to match myocardial tissue improves electrical connectivity between healthy and infarcted areas and increases electrical conduction velocity and synchronization. Overall, the MEHP combined with cell therapy effectively prevents ventricular fibrosis and remodeling, promotes neovascularization, and restores electrical propagation and synchronized pulsation, facilitating the clinical translation of cardiac tissue engineering.


Assuntos
Hidrogéis , Infarto do Miocárdio , Humanos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Miocárdio , Infarto do Miocárdio/tratamento farmacológico , Condutividade Elétrica , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia
15.
ACS Appl Mater Interfaces ; 14(40): 45869-45879, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36165460

RESUMO

Underwater adhesion plays an essential role in soft electronics for the underwater interface. Although hydrogel-based electronics are of great interest, because of their versatility, water molecules prevent hydrogels from adhering to substrates, thus bottlenecking further applications. Herein, inspired by the barnacle proteins, MXene/PHMP hydrogels with strong repeatable underwater adhesion are developed through the random copolymerization of 2-phenoxyethyl acrylate, 2-methoxyethyl acrylate, and N-(2-hydroxyethyl) acrylamide with the presence of MXene nanosheets. The hydrogels are mechanically tough (elastic modulus of 32 kPa, fracture stress of 0.11 MPa), and 2-phenoxyethyl acrylate (PEA) with aromatic groups endows the hydrogel with nonswelling property and prevents water molecules from invading the adhesive interface, rendering the hydrogels an outstanding adhesive behavior toward various substrates (including glass, iron, polyethylene terephthalate (PET), porcine). Besides, dynamic physical interactions allow for instant and repeatable underwater adhesion. Furthermore, the MXene/PHMP hydrogels exhibit a high conductivity (0.016 S/m), fast responsiveness, and superior sensitivity as a strain sensor (gauge factor = 7.17 at 200%-500% strain) and pressure sensor (0.63 kPa-1 at 0-70 kPa). The underwater applications of bionic hydrogel-based sensors have been demonstrated, such as human motion, pressure sensing, and holding objects. It is anticipated that the instant and repeatable underwater adhesive hydrogel-based sensors extend the underwater applications of hydrogel electronics.


Assuntos
Adesivos , Hidrogéis , Acrilamidas , Acrilatos , Adesivos/química , Animais , Condutividade Elétrica , Humanos , Hidrogéis/química , Ferro , Polietilenotereftalatos , Suínos , Água
16.
Nat Commun ; 13(1): 5339, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096894

RESUMO

Zwitterionic hydrogels exhibit eminent nonfouling and hemocompatibility. Several key challenges hinder their application as coating materials for blood-contacting biomedical devices, including weak mechanical strength and low adhesion to the substrate. Here, we report a poly(carboxybetaine) microgel reinforced poly(sulfobetaine) (pCBM/pSB) pure zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties. The pCBM/pSB hydrogel coating was bonded to the PVC substrate via the entanglement network between the pSB and PVC chain. Moreover, the pCBM/pSB hydrogel coating can maintain favorable stability even after 21 d PBS shearing, 0.5 h strong water flushing, 1000 underwater bends, and 100 sandpaper abrasions. Notably, the pCBM/pSB hydrogel coated PVC tubing can not only mitigate the foreign body response but also prevent thrombus formation ex vivo in rats and rabbits blood circulation without anticoagulants. This work provides new insights to guide the design of pure zwitterionic hydrogel coatings for biomedical devices.


Assuntos
Hidrogéis , Microgéis , Animais , Hidrogéis/química , Cloreto de Polivinila , Coelhos , Ratos
17.
Acta Biomater ; 151: 163-173, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35944810

RESUMO

Postoperative peritoneal adhesion is a common complication after surgery with high morbidity. In addition to improving surgical operations, medical therapy and physical barriers are the two main ways to prevent postoperative peritoneal adhesion. Satisfactory efficacy is not often obtained by the single antiadhesion method, and the combination of barrier therapy and antiadhesion drugs has attracted more attention. In this study, we first demonstrated that aberrant complement activation was associated with peritoneal injury and inflammatory responses. Correspondingly, blocking the C5a-C5aR axis reaction effectively reduced inflammatory reactions. Therefore, we creatively developed an integrated treatment of xyloglucan derivative (mXG) hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) aimed at peritoneal adhesion, and then systematically evaluated the therapeutic efficacy using a sidewall defect-cecum abrasion model in mice. In vitro and in vivo experiments showed that the mXG hydrogel had good biocompatibility and degradability and could serve as a safe anti-adhesion barrier. The results showed that anti-C5aRab treatment could significantly inhibit peritoneal adhesions by reducing neutrophil infiltration and the expression of phosphorylated Smad2. Taken together, the mXG hydrogel integrated with anti-C5aRab showed superior antiadhesion performance and holds promising clinical applications in preventing peritoneal adhesion. STATEMENT OF SIGNIFICANCE: Postoperative peritoneal adhesion is an urgent problem to be solved after surgery. Previously, a biodegradable and thermoreversible xyloglucan derivative (mXG) hydrogel was developed that effectively prevented postoperative peritoneal adhesions, but obvious inflammatory responses and proliferation could still be observed. In addition, aberrant complement activation is associated with a variety of inflammatory diseases. We demonstrated that aberrant complement activation is involved in peritoneal adhesion. In this work, mXG hydrogel and intravenous anti-C5a receptor antibody (anti-C5aRab) were integrated to address peritoneal adhesions. The anti-C5aRab reduced the inflammatory responses. In addition, the mXG hydrogel was easy to use and effectively isolated the wound surface at the local injury site. Overall, this integrated treatment significantly improved the antiadhesion effect.


Assuntos
Hidrogéis , Receptor da Anafilatoxina C5a , Animais , Glucanos/farmacologia , Hidrogéis/farmacologia , Camundongos , Aderências Teciduais/prevenção & controle , Xilanos/farmacologia , Xilanos/uso terapêutico
18.
Acta Biomater ; 151: 290-303, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35995406

RESUMO

Zwitterionic polymers have shown promising results in non-fouling and preventing thrombosis. However, the lack of controlled surface coverage hinders their application for biomedical devices. Inspired by the natural biological surfaces, a facile zwitterionic microgel-based coating strategy is developed by the co-deposition of poly (sulfobetaine methacrylate-co-2-aminoethyl methacrylate) microgel (SAM), polydopamine (PDA), and sulfobetaine-modified polyethyleneimine (PES). The SAMs were used to construct controllable morphology by using the PDA combined with PES (PDAS) as the intermediate layer, which can be easily modulated via adjusting the crosslinking degree and contents of SAMs. The obtained SAM/PDAS coatings exhibit high anti-protein adhesive properties and can effectively inhibit the adhesion of cells, bacteria, and platelet through the synergy of high deposition density and controllable morphology. In addition, the stability of SAM/PDAS coating is improved owing to the anchoring effects of PDAS to substrate and SAMs. Importantly, the ex vivo blood circulation test in rabbits suggests that the SAM/PDAS coating can effectively decrease thrombosis without anticoagulants. This study provides a versatile coating method to address the integration of zwitterionic microgel-based coatings with high deposition density and controllable morphology onto various substrates for wide biomedical device applications. STATEMENT OF SIGNIFICANCE: Thrombosis is a major cause of medical device implantation failure, which results in significant morbidity and mortality. In this study, inspired by natural biological surfaces (fish skin and vascular endothelial layer) and the anchoring ability of mussels, we report a convenient and efficient method to firmly anchor zwitterionic microgels using an oxidative co-deposition strategy. The prepared coating has excellent antifouling and antithrombotic properties through the synergistic effect of physical morphology and chemical composition. This biomimetic surface engineering strategy is expected to provide new insights into the clinical problems of blood-contacting devices related to thrombosis.


Assuntos
Microgéis , Animais , Anticoagulantes , Betaína/análogos & derivados , Fibrinolíticos , Metacrilatos , Polietilenoimina/farmacologia , Polímeros/química , Coelhos , Propriedades de Superfície
19.
Macromol Rapid Commun ; 43(17): e2200182, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35640482

RESUMO

Traditional adhesives such as cyanoacrylate glue are mostly solvent-based. They are facing the problem of insufficient adhesion to some substrates, and also from the drawback of volatilization and release of small organic molecules in the process of usage. Therefore, a novel adhesive with non-irritating, high adhesive strength, and antibacterial properties is highly required. In this study, a full physically crosslinked zwitterionic poly(betaine sulfonate methacrylate) (PSBMA) hydrogel is proposed. The physical crosslinking interactions endow the hydrogel with good self-healing properties. Furthermore, the pure physical crosslinking hydrogel can form PSBMA powder adhesive after lyophilization and return to the hydrogel state after hydration. The mechanical properties of PSBMA adhesive can be modulated via adjusting the solid content and initiator dosage. Following the cure process similar to that of snail mucus or insect exoskeletons in nature, the adhesion of the PSBMA adhesive is improved at least 100 times than its wet state. In addition, the PSBMA adhesive is easy to be removed due to the dissociation of cross-linked structures in saltwater environments. Moreover, PSBMA adhesive with antifouling properties can effectively prevent the adhesion of proteins and bacteria, which shows potential applications in the assembly of medical devices.


Assuntos
Hidrogéis , Adesivos Teciduais , Adesivos/química , Antibacterianos/química , Antibacterianos/farmacologia , Betaína , Hidrogéis/química , Metacrilatos/química , Adesivos Teciduais/farmacologia
20.
J Mater Chem B ; 10(13): 2215-2229, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35289348

RESUMO

To improve the therapeutic effect of a hydrogel on damaged tissue, a series of hydroxybutyl chitosan (HBC) and poly(sulfobetaine methacrylate) (PSBMA) composite hydrogels (HBC-PSB) with thermosensitivity, self-healing, antibiofouling, and synergistic antibacterial activity are prepared by mechanical blending. The electrostatic interaction among PSBMA and hydrophobic association among HBC are the main drive force to form a full physically crosslinked hydrogel. HBC can avoid the aggregation and precipitation of PSBMA caused by intermolecular strong association. Meanwhile, the existence of the PSBMA network can promote the sol-gel transition of HBC. Due to the reversible physical crosslinking, the HBC-PSB hydrogel shows excellent self-healing behaviors, and can be stored as dry powder. Intriguingly, the composite hydrogel has good synergistic antibacterial performance via the anti-protein adhesion ability of the PSBMA network and bactericidal ability of the HBC network. Based on these results, a sidewall defect-cecum abrasion model and an infected full-thickness skin defect model are used to investigate the application of the prepared HBC-PSB hydrogel in postoperative anti-adhesion and healing of infected wounds, respectively. The results suggest that the HBC-PSB hydrogel can completely cover the irregular damaged tissue surface, moreover, it can effectively decrease the formation of postoperative adhesion and improve the healing speed of infected wounds via reducing the adhesion and growth of bacteria. Overall, we propose that the HBC-PSB hydrogel is a promising candidate in biomedical applications.


Assuntos
Hidrogéis , Infecção dos Ferimentos , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Metacrilatos/farmacologia , Pós/farmacologia , Cicatrização
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