RESUMEN
Combination immunotherapy is being increasingly explored for cancer treatment, leading to various vector materials for the codelivery of immune agents and drugs. However, current tumor vaccines exhibit poor immunogenicity, severely compromising their therapeutic efficacy. Herein, an injectable hydrogel was developed based on dopamine (DA) and Panax notoginseng polysaccharide (PNPS) loaded with hair microparticles (HMPs) to enhance the immunogenicity of tumor vaccines. Photothermal effects of incorporated HMPs can trigger immunogenic cancer cell death and the release of abundant autologous tumor antigens, which are captured by catechol groups. Concomitant breakdown of PNPS recruits and activates dendritic cells (DCs). The macroporous structure of cryogels allows immune cell infiltration and interaction with antigens adsorbed on PNPS and DA cryogels (PD cryogels), thereby provoking potent cytotoxic T-cell responses. Hence, PD cryogels enabling cell infiltration and accelerated DC maturation may serve as a therapeutic vaccination platform against cancer.
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Vacunas contra el Cáncer , Criogeles , Células Dendríticas , Panax notoginseng , Polisacáridos , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Criogeles/química , Criogeles/farmacología , Panax notoginseng/química , Animales , Ratones , Polisacáridos/química , Polisacáridos/farmacología , Células Dendríticas/inmunología , Humanos , Femenino , Ratones Endogámicos C57BL , Línea Celular TumoralRESUMEN
Skin injuries can have unexpected surfaces, leading to uneven wound surfaces and inadequate dressing contact with these irregular surfaces. This can decrease the dressing's haemostatic action and increase the healing period. This study recommends the use of sticky and flexible cryogel coverings to promote faster haemostasis and efficiently handle uneven skin wounds. Alginate cryogels have a fast haemostatic effect and shape flexibility due to their macroporous structure. The material demonstrates potent antibacterial characteristics and enhances skin adherence by adding grafted chitosan with gallic acid. In irregular defect wound models, cryogels can cling closely to uneven damage surfaces due to their amorphous nature. Furthermore, their macroporous structure allows for quick haemostasis by quickly absorbing blood and wound exudate. After giving the dressing a thorough rinse, its adhesive strength reduces and it is simple to remove without causing any damage to the wound. Cryogel demonstrated faster haemostasis than gauze in a wound model on a rat tail, indicating that it has considerable potential for use as a wound dressing in the biomedical area.
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Vendajes , Criogeles , Hemostasis , Cicatrización de Heridas , Criogeles/farmacología , Animales , Cicatrización de Heridas/efectos de los fármacos , Ratas , Hemostasis/efectos de los fármacos , Polisacáridos/farmacología , Quitosano/farmacología , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Alginatos/farmacología , Masculino , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/terapia , Hemostáticos/farmacología , Piel/lesionesRESUMEN
In this work, we have demonstrated agar and oxidized bacterial cellulose cryogels as a potential hemostatic dressing material. TEMPO-oxidized bacterial cellulose (OBC) was incorporated into the agar matrix, improving its mechanical and hemostatic properties. The oxidation of bacterial cellulose (BC) was evidenced by chemical characterization studies, confirming the presence of carboxyl groups. The in vitro blood clotting test conducted on agar/OBC composite cryogels demonstrated complete blood clotting within 90 seconds, indicating their excellent hemostatic efficacy. The cryogels exhibited superabsorbent properties with a swelling degree of 4200%, enabling them to absorb large amounts of blood. Moreover, the compressive strength of the composite cryogels was appreciably improved compared to pure agar, resulting in a more stable physical structure. The platelet adhesion test proved the significant ability of the composite cryogels to adhere to and aggregate platelets. Hemocompatibility and cytocompatibility tests have verified the safety of these cryogels for hemostatic applications. Finally, the material exhibited remarkable in vivo hemostatic performance, achieving clotting times of 64 seconds and 35 seconds when tested in the rat tail amputation model and the liver puncture model, respectively. The experiment results were compared with those of commercial hemostat, Axiostat, and Surgispon, affirming the potential of agar/OBC composite cryogel as a hemostatic dressing material.
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Celulosa Oxidada , Hemostáticos , Ratas , Animales , Hemostáticos/farmacología , Hemostáticos/química , Celulosa Oxidada/farmacología , Criogeles/farmacología , Criogeles/química , Agar , Celulosa/farmacologíaRESUMEN
Wounds infected with multidrug-resistant (MDR) bacteria are increasingly threatening public health and challenging clinical treatments because of intensive bacterial colonization, excessive inflammatory responses, and superabundant oxidative stress. To overcome this malignant burden and promote wound healing, a multifunctional cryogel (HA/TA2/KR2) composed of hyaluronic acid (HA), tannic acid (TA), and KR-12 peptides is designed. The cryogel exhibited excellent shape-memory properties, strong absorption performance, and hemostatic capacity. In vitro experiments demonstrated that KR-12 in the cryogel can be responsively released by stimulation with hyaluronidase produced by bacteria, reaching robust antibacterial activity against Escherichia coli (E. coli), MDR Pseudomonas aeruginosa (MDR-PA), and methicillin-resistant Staphylococcus aureus (MRSA) by disrupting bacterial cell membranes. Furthermore, the synergetic effect of KR-12 and TA can efficiently scavenge ROS and decrease expression of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α & interleukin (IL)-6), as well as modulate the macrophage phenotype toward the M2 type. In vivo animal tests indicated that the cryogel can effectively destroy bacteria in the wound and promote healing process via accelerating angiogenesis and re-epithelialization. Proteomic analysis revealed the underlying mechanism by which the cryogel mainly reshaped the infected wound microenvironment by inhibiting the Nuclear factor kappa B (NF-κB) signaling pathway and activating the Janus kinase-Signal transducer and activator of transcription (JAK-STAT6) signaling pathway. Therefore, the HA/TA2/KR2 cryogel is a promising dressing candidate for MDR bacteria-infected wound healing.
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Antibacterianos , Criogeles , Modelos Animales de Enfermedad , Hialuronoglucosaminidasa , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Animales , Ratones , Antibacterianos/farmacología , Criogeles/farmacología , Criogeles/química , Escherichia coli/efectos de los fármacos , Ácido Hialurónico/farmacología , Hialuronoglucosaminidasa/metabolismo , Inflamación/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Ratones Endogámicos BALB CRESUMEN
Improvement of mechanical properties of injectable tissue engineering scaffolds is a current challenge. The objective of the current study is to produce a highly porous injectable scaffold with improved mechanical properties. For this aim, cellulose nanocrystals-reinforced dual crosslinked porous nanocomposite cryogels were prepared using chemically crosslinked methacrylated gelatin (GelMA) and ionically crosslinked hyaluronic acid (HA) through the cryogelation process. The resulting nanocomposites showed highly porous structures with interconnected porosity (>90%) and mean pore size in the range of 130-296 µm. The prepared nanocomposite containing 3%w/v of GelMA, 20 w/w% of HA, and 1%w/v of CNC showed the highest Young's modulus (10 kPa) and excellent reversibility after 90% compression and could regain its initial shape after injection by a 16-gauge needle in the aqueous media. The in vitro results demonstrated acceptable viability (>90%) and migration of the human chondrocyte cell line (C28/I2), and chondrogenic differentiation of human adipose stem cells. A two-month in vivo assay on a rabbit's ear model confirmed that the regeneration potential of the prepared cryogel is comparable to the natural autologous cartilage graft, suggesting it is a promising alternative for autografts in the treatment of cartilage defects.
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Nanocompuestos , Nanopartículas , Animales , Conejos , Humanos , Criogeles/farmacología , Criogeles/química , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Gelatina/farmacología , Gelatina/química , Celulosa/farmacología , Celulosa/química , Andamios del Tejido/química , Cartílago , Ingeniería de Tejidos/métodos , Nanopartículas/química , PorosidadRESUMEN
Scaffold-based cell delivery can improve therapeutic effects of transplanted cells in cell therapy. Biomaterial scaffolds serveas niche for cell growth and proliferation which improves cell survival and overall function post cell delivery. In this study, gelatin methacryloyl based injectable scaffolds made using poly(ethylene)glycol as a sacrificial polymer and cryogelation as a technique, are demonstrated to have tunable degradability and porosity that is required for cell and drug delivery applications. The pore size (10-142 µm) of these gels makes them suitable for loading different cell types as per the application. In vitro studies using mammalian cells confirm that these cryogels are cytocompatible. These cell-laden scaffolds are injectable and have a cell retention ability of up to 90% after injection. Rheology is done to evaluate stiffness and shape recovery property, and it is found that these gels can maintain their original shape even after applying 7 cycles of strain from 0.1% to 20%. Furthermore, their degradability can be modulated between 6 and 10 days by changing the overall polymer composition. Thus, injectability and degradability of these cryogels can circumvent invasive surgical procedures, thereby making them useful for a variety of applications including delivery of cells and bioactive factors.
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Materiales Biocompatibles , Criogeles , Metacrilatos , Animales , Criogeles/farmacología , Materiales Biocompatibles/farmacología , Gelatina/farmacología , Geles/farmacología , Polímeros/farmacología , Andamios del Tejido , Porosidad , Ingeniería de Tejidos/métodos , Proliferación Celular , MamíferosRESUMEN
The treatment for diabetic ulcers still remains a big clinic challenge owing to the adverse repair microenvironment. Bioactive glasses (BGs) play an important role in the late stages of healing due to their ability to promote vascularization and collagen fiber deposition, but fail to improve infection and oxidative stress in the early stage.Therefore, it is critical to develop a material involved in regulating the whole healing phases. In this work, BGs-based nanozymes (MnO2 @PDA-BGs) with antioxidation, antibacterial and pro-healing abilities are synthesized by the redox deposition of MnO2 on mesoporous BGs. Afterward, cryogel with the interconnected macropore structure is fabricated by the polymerization of methacrylate anhydride gelatin (GelMA) at -20 °C. MnO2 @PDA-BGs are loaded into the cryogel to obtain nanocomposite cryogel (MnO2 @PDA-BGs/Gel) with multiple enzymes-like- activities to eliminate reactive oxygen species (ROS). Besides, MnO2 @PDA-BGs/Gel has intensive peroxidase-like activity under acidic condition and near infrared photothermal responsiveness to achieve excellent antibacterial performance. Cells experiments demonstrate that MnO2 @PDA-BGs/Gel recruits L929s and promotes their proliferation. Furthermore, MnO2 @PDA-BGs/Gel eliminates intracellular overexpressed ROS and maintains the viability of L929s. Animal experiments confirm that MnO2 @PDA-BGs/Gel promotes wound healing and avoided scarring by killing bacteria, reversing inflammation, promoting vascularization, and improving the deposition of collagen III.
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Antioxidantes , Diabetes Mellitus , Animales , Antioxidantes/farmacología , Criogeles/farmacología , Compuestos de Manganeso , Especies Reactivas de Oxígeno , Óxidos , Antibacterianos/farmacología , ColágenoRESUMEN
Self-expanding cryogels hold unique prospects for treating uncontrollable hemorrhages. However, development of a mechanically robust, tissue-adhesive, and bioactive self-expanding cryogel enabling effective hemostasis and tissue repair has remained a great challenge. Herein, we report a superelastic cellular-structured bioactive glass nanofibrous cryogel (BGNC) composed of highly flexible BG nanofibers and citric acid-cross-linked poly(vinyl alcohol). These BGNCs exhibit high absorption capacity (3169%), fast self-expanding ability, near zero Poisson's ratio, injectability, high compressive recovery at a strain of 80%, robust fatigue resistance (almost no plastic deformation after 800 cycles at a strain of 60%), and good adhesion with diverse tissues. The BGNCs provide sustained release of Ca, Si, and P ions. Moreover, the BGNCs present better blood clotting and blood cell adhesion ability and superior hemostatic capacity in rabbit liver and femoral artery hemorrhage models as compared with commercial gelatin hemostatic sponges. In addition, BGNCs are able to stop bleeding in rat cardiac puncture injury in about 1 min. Furthermore, the BGNCs are capable of promoting rat full-thickness skin wound healing. The development of self-expanding BGNCs with superelasticity and bioadhesion provides a promising strategy for exploring multifunctional hemostatic and wound repair materials.
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Hemostáticos , Nanofibras , Ratas , Animales , Conejos , Criogeles/farmacología , Cicatrización de Heridas , Hemostasis , Hemostáticos/farmacología , Hemorragia , Antibacterianos/farmacologíaRESUMEN
Bone tissue engineered scaffolds are designed to mimic the natural environment for regeneration when typical healing is inhibited. Autografts are the current gold standard for treatment but are limited by available bone and supplementary surgical sites that broaden complications and comorbidities. Cryogels are an ideal scaffold in bone regeneration due to their mechanical integrity and marcoporous structure that elicits angiogenesis and subsequently new bone tissue formation. To aid in bioactivity and osteoinductivity, manuka honey (MH) and bone char (BC) were added to gelatin and chitosan cryogels (CG). Manuka honey has powerful antimicrobial properties to aid against graft infection, and bone char is composed of 90% hydroxyapatite, a well-studied bioactive material. These additives are natural, abundant, easy to use, and cost effective. CG cryogels incorporated with either BC or MH, and plain CG cryogels were implanted into rat calvarial fracture models for cortical bone regeneration analysis. We found indication of bioactivity with both bone char and manuka honey through the presence of woven bone structure in histology stains and micro computed tomography (microCT) data. Overall, plain CG cryogels supported greater bone regeneration capabilities than the BC or MH incorporated cryogels due to a lack of advanced organized tissue formation and collagen deposition after 8 weeks of implantation; however, future work should explore varying additive concentrations and delivery methods to further assess additive potential.
Asunto(s)
Quitosano , Miel , Ratas , Animales , Quitosano/farmacología , Quitosano/química , Criogeles/farmacología , Criogeles/química , Gelatina/farmacología , Gelatina/química , Ingeniería de Tejidos/métodos , Microtomografía por Rayos X , Andamios del Tejido/química , HuesosRESUMEN
Chemoimmunotherapy is an effective method to treat cancer, and thus various vehicles have been constructed to co-deliver immune agents and anticancer drugs. But the immune induction process in vivo is highly susceptible to the influence of the material itself. To avoid immune reactions by the materials of delivery systems, herein, a new kind of zwitterionic cryogels (SH cryogels) with extremely low immunogenicity was prepared for chemoimmunotherapy of cancer. Their macroporous structure enabled the SH cryogels to have good compressibility and be injected through a conventional syringe. The loaded chemotherapeutic drugs and immune adjuvants were accurately, locally and long-termly released in the vicinity of tumors, enhancing the outcome of tumor therapy and minimizing the damage caused by the chemotherapeutic drugs to other organ tissues. In vivo tumor treatment experiments indicated that chemoimmunotherapy using the SH cryogel platform could inhibit the growth of breast cancer tumors to the greatest extent. Furthermore, macropores of SH cryogels supported cells to move freely in the cryogels, which could promote the dendritic cells to capture the in situ produced tumor antigens and present them to T cells. The ability to act as cradles for cell infiltration made the SH cryogels promising for applications as vaccine platforms.
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Criogeles , Linfocitos T , Criogeles/química , Criogeles/farmacologíaRESUMEN
Cryogels are support materials which are good at mimicking extracellular matrix due to their excellent hydrophilicity, biocompatibility, and macroporous structure, thus they are useful in facilitating cell activities during healing process. In this study, polyvinyl alcohol-gelatin (PVA-Gel) based cryogel membranes loaded with pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene; PTS) (PVA-Gel/PTS) was synthesized as wound dressing materials. PVA-Gel and PVA-Gel/PTS were synthesized with the polymerization yields of 96% ± 0.23% and 98% ± 0.18%, respectively, and characterized by swelling tests, Brunauer-Emmett-Teller (BET) and scanning electron microscopy (SEM) analysis. The swelling ratios were calculated as 98.6% ± 4.93% and 102% ± 5.1%, macroporosities were determined as 85% ± 2.13% and 88% ± 2.2%, for PVA-Gel and PVA-Gel/PTS, respectively. It was determined that PVA-Gel and PVA-Gel/PTS have 17 m2 /g ± 0.76 m2 /g and 20 m2 /g ± 0.92 m2 /g surface areas, respectively. SEM studies were demonstrated that they have ~100 µm pore sizes. According to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results, it was observed that cell proliferation, cell number and cell viability were higher in PVA-Gel/PTS cryogel at 24, 48, and 72 h compared to PVA-Gel. A strong and transparent fluorescent light intensity was observed indicating higher cell population in PVA-Gel/PTS in comparison with PVA-Gel, according to 4',6-diamidino-2-phenylindole (DAPI) staining. SEM, F-Actin, Giemsa staining and inverted-phase microscope image of fibroblasts in PVA-Gel/PTS cryogels revealed that dense fibroblast proliferation and spindle-shaped morphology of cells were preserved. Moreover, DNA agarose gel data demonstrated that PVA-Gel/PTS cryogels had no effect on DNA integrity. Consequently, produced PVA-Gel/PTS cryogel can be used as wound dressing material to promote wound therapies, inducing cell viability and proliferation.
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Criogeles , Alcohol Polivinílico , Criogeles/farmacología , Alcohol Polivinílico/farmacología , Alcohol Polivinílico/química , Gelatina/farmacología , Gelatina/química , VendajesRESUMEN
Tough porous cryogels with angiogenesis and osteogenesis features remain a design challenge for utility in bone regeneration. Here, building off of the recent efforts to generate tough silk nanofiber-derived cryogels with osteogenic activity, deferoxamine (DFO) is loaded in silk nanofiber-derived cryogels to introduce angiogenic capacity. Both the mechanical cues (stiffness) and the sustained release of DFO from the gels are controlled by tuning the concentration of silk nanofibers in the system, achieving a modulus above 400 kPa and slow release of the DFO over 60 days. The modulus of the cryogels and the released DFO induce osteogenic and angiogenic activity, which facilitates bone regeneration in vivo in femur defects in rat, resulting in faster regeneration of vascularized bone tissue. The tunable physical and chemical cues derived from these nanofibrous-microporous structures support the potential for silk cryogels in bone tissue regeneration.
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Nanofibras , Osteogénesis , Ratas , Animales , Criogeles/farmacología , Criogeles/química , Seda/farmacología , Porosidad , Andamios del Tejido/química , Regeneración ÓseaRESUMEN
Uncontrolled hemorrhage is a main cause of pre-hospital death. Given the importance of hemostatic wound dressings in pre-hospital emergency treatment, novel composite materials are required for fast hemostasis, synergistic bacterial ablation with negligible resistance and wound healing acceleration. Herein, multifunctional SCTF cryogels were fabricated by the simultaneous cross-linking of sodium alginate (SA) and tannic acid (TA) with Fe3+ ions. As a result, the prepared SCTF cryogels consisted of Fe3+/TA-based metal phenolic networks (MPNs) and Fe3+/SA-based 3D skeleton for collagen (CA). MPNs endowed the cryogels with photothermal effect, photothermal-enhanced Fenton activity and pH/photothermal dual-responsive release property of TA and Fe2+, which were beneficial for the antibacterial capacity. Due to the intrinsic high porosity, in vitro and in vivo assays demonstrated that SCTF cryogels possessed good hemostatic capacity. Moreover, the synergistic photothermal therapy (PTT), chemodynamic therapy (CDT) and pH/photothermal responsive chemo-therapy dramatically enhanced the bactericidal efficacy of SCTF cryogels both in vitro and in vivo. Eventually, their outstanding healing-accelerating effects were confirmed via animal experiments, which were attributed to the presence of CA and TA. Therefore, the developed composite materials could offer new strategy on exploiting multifunctional wound dressing for clinical applications in the future.
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Criogeles , Hemostáticos , Animales , Criogeles/farmacología , Alginatos/farmacología , Cicatrización de Heridas , Colágeno , Metales , Antibacterianos/farmacologíaRESUMEN
Uncontrolled bleeding is one of the most important causes threatening human health, but quick hemostasis remains a challenge. We prepared porous cryogels with poly ß-cyclodextrin (Pß-CD) and quaternary ammoniated chitosan (QCs). Pß-CD acts as a "water-grabbing agent" to assist QCs' ability to absorb and concentrate blood rapidly. The rat-tail amputation model and liver injury model exhibited that cryogels had excellent hemostatic performance. Moreover, cryogels showed good antibacterial activity and biocompatibility. Therefore, these cryogels can be used as potential hemostatic materials.
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Quitosano , Hemostáticos , Humanos , Ratas , Animales , Quitosano/farmacología , Criogeles/química , Criogeles/farmacología , Porosidad , Hemostasis , Hemostáticos/farmacología , Hemostáticos/químicaRESUMEN
Dendritic cells (DCs), professional antigen-presenting cells, function as sentinels of the immune system. DCs initiate and fine-tune adaptive immune responses by presenting antigenic peptides to B and T lymphocytes to mount an effective immune response against cancer and pathogens. However, hypoxia, a condition characterized by low oxygen (O2) tension in different tissues, significantly impacts DC functions, including antigen uptake, activation and maturation, migration, as well as T-cell priming and proliferation. In this study, we employed O2-releasing biomaterials (O2-cryogels) to study the effect of localized O2 supply on human DC phenotype and functions. Our results indicate that O2-cryogels effectively mitigate DC exposure to hypoxia under hypoxic conditions. Additionally, O2-cryogels counteract hypoxia-induced inhibition of antigen uptake and migratory activity in DCs through O2 release and hyaluronic acid (HA) mediated mechanisms. Furthermore, O2-cryogels preserve and restore DC maturation and co-stimulation markers, including HLA-DR, CD86, and CD40, along with the secretion of proinflammatory cytokines in hypoxic conditions. Finally, our findings demonstrate that the supplemental O2 released from the cryogels preserves DC-mediated T-cell priming, ultimately leading to the activation and proliferation of allogeneic CD3+ T cells. This work emphasizes the potential of local oxygenation as a powerful immunomodulatory agent to improve DC activation and functions in hypoxia, offering new approaches for cancer and infectious disease treatments.
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Células Dendríticas , Neoplasias , Humanos , Materiales Biocompatibles/farmacología , Criogeles/farmacología , Fenotipo , Antígenos/farmacología , HipoxiaRESUMEN
The potential of chitosan and carboxymethyl chitosan (CMC) cryogels cross-linked with diglycidyl ether of 1,4-butandiol (BDDGE) and poly(ethylene glycol) (PEGDGE) have been compared in terms of 3D culturing HEK-293T cell line and preventing the bacterial colonization of the scaffolds. The first attempts to apply cryogels for the 3D co-culturing of bacteria and human cells have been undertaken toward the development of new models of host-pathogen interactions and bioimplant-associated infections. Using a combination of scanning electron microscopy, confocal laser scanning microscopy, and flow cytometry, we have demonstrated that CMC cryogels provided microenvironment stimulating cell-cell interactions and the growth of tightly packed multicellular spheroids, while cell-substrate interactions dominated in both chitosan cryogels, despite a significant difference in swelling capacities and Young's modulus of BDDGE- and PEGDGE-cross-linked scaffolds. Chitosan cryogels demonstrated only mild antimicrobial properties against Pseudomonas fluorescence, and could not prevent the formation of Staphylococcus aureus biofilm in DMEM media. CMC cryogels were more efficient in preventing the adhesion and colonization of both P. fluorescence and S. aureus on the surface, demonstrating antifouling properties rather than the ability to kill bacteria. The application of CMC cryogels to 3D co-culture HEK-293T spheroids with P. fluorescence revealed a higher resistance of human cells to bacterial toxins than in the 2D co-culture.
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Quitosano , Criogeles , Humanos , Criogeles/farmacología , Criogeles/química , Quitosano/farmacología , Quitosano/química , Técnicas de Cocultivo , Células HEK293 , Staphylococcus aureus , Polietilenglicoles , Riñón , ÉteresRESUMEN
Shape-memory cryogels have drawn attention as an injectable system to minimize the risks associated with surgical implantation in tissue engineering. To achieve shape memory behavior with hydration as an external stimulus, it is necessary to have a porous elastic network. To achieve this, it is crucial to control the crosslinking process at the time of pore formation, especially for natural-based polymers. In this study, a versatile method using a cryogelation method in the presence of chemical and physical crosslinkers is investigated to obtain an injectable super macroporous elastic structure based on a poly(ampholyte) (carboxymethyl chitosan) and a protein (gelatin). Mechanical, swelling, shape memorizing behavior, injectability, and in vitro and in vivo behavior of cryogels were studied. Cryogelation in a subzero temperature led to the formation of scaffolds with interconnected pores of the size of 350 µm which swelled completely after 3 min. Cryogels had crosslink density up to 22% and elastic modulus in the hydrated state up to 0.054 and 1.733 MPa at low and high strains, respectively, and low hysteresis (<30 kPa). Injectability studies confirmed the ability of the cryogels to be injected through a 16G needle. In vitro studies demonstrated good cellular penetration, cell adhesion, and high cell viability (>100%). In vivo studies using mice showed that the body's response was befitting without inflammation and any side effect for the liver and kidneys.
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Quitosano , Criogeles , Animales , Tampones (Química) , Quitosano/química , Criogeles/química , Criogeles/farmacología , Gelatina/química , Gelatina/farmacología , Ratones , Polímeros , Porosidad , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
Wound dressings that promote quick hemostasis and are highly efficient in healing wounds are urgently needed to meet the increase in clinical demands worldwide. Herein, a dihydrazide-modified waterborne biodegradable polyurethane emulsion (PU-ADH) and oxidized hyaluronic acid (OHA) were autonomously cross-linked to form a hybrid hyaluronic acid-polyurethane (HA-PU) cryogel by hydrazone bonding at -20 °C. Through its specific macroporous structure (which is approximately 220 µm) constructed by aggregated PU-ADH particles and long-chain OHA, a dried cryogel can have a dramatically compressed volume (1/7 of its original volume) with stable fixation, and it can swell rapidly by absorbing water or blood to approximately 22 and 16 times its dried weight, respectively, in a few minutes. This instantaneous shape-recovering ability favors fast hemostasis in minimally invasive surgery. Moreover, this cryogel is superior to gauze, has excellent biocompatibility, and quickly coagulates blood (in approximately 2 min) by activating the endogenous coagulation system. Comparably, an injectable HA-PU hydrogel with the same components as the HA-PU cryogel was prepared at room temperature, and it exhibited good self-healing properties. An in vivo evaluation of a rat liver hemostasis model and rat skin defect model revealed that the cryogel in fast hemostasis has great potential and superior wound-healing abilities, decreases immune inflammation, and promotes the regeneration of angiogenesis and hair follicles. Consequently, this work proposes a versatile method for constructing biodegradable hybrid cryogels via autonomous cross-linking between synthesized polymer emulsions and natural polymers. The hybrid cryogels demonstrated great potential for applications as high-performance wound dressings.
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Criogeles , Ácido Hialurónico , Animales , Criogeles/química , Criogeles/farmacología , Hemostasis , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Polímeros/química , Poliuretanos/farmacología , Ratas , Cicatrización de HeridasRESUMEN
Cryogels, with high water/blood absorption, have great potential for rapid hemostasis. In this study, a hemostatic and antibacterial sericin-methacryloyl/Ag cryogel (SMC@Ag) based on freeze polymerization of methacryloyl-modified sericin and in situ reduction of silver ions is developed. The combination of interconnected micropores and Ag NPs endows the cryogel with high water/blood absorption, and outstanding hemostatic and antibacterial performance. SMC@Ag shows much better hemostatic performance than the commercial gelatin sponge in rat liver injury, tail amputation, and femoral artery injury models. Furthermore, the excellent hemostatic activity of SMC@Ag is due to facilitating the coagulation pathway activation and enhancing the platelets adhesion during coagulation process. Overall, SMC@Ag cryogel with excellent hemostatic and antibacterial performance is a suitable candidate for traumatic hemorrhage and wound healing.
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Hemostáticos , Sericinas , Animales , Antibacterianos/farmacología , Plaquetas , Criogeles/farmacología , Hemostasis , Hemostáticos/farmacología , Ratas , Sericinas/farmacología , AguaRESUMEN
Burn wounds are susceptible to bacterial infections and are usually accompanied by a large amount of exudate, making the treatment of burn wounds a challenge in the clinic. Here, we developed a biodegradable cryogel with high water absorption and good antibacterial and antibiofilm activity based on gelatin (GT) and silver nanoparticles (Ag NPs) to promote burn wound healing. The porous GT/Ag cryogel had a swelling ratio of up to 4000%, effectively absorbing wound exudate and allowing for gas exchange. Moreover, the GT/Ag cryogel had an excellent killing effect on methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA), which burn wounds are susceptible to, and can effectively remove mature biofilms. In the rat liver defect noncompressible hemorrhage model, GT/Ag cryogels with shape memory performance showed better hemostatic ability than commercial gelatin sponges. Most importantly, the GT/Ag cryogel was more effective than the TegadermTM dressing and GT cryogel in promoting wound contraction, collagen deposition, and angiogenesis and reducing inflammation in a PA-infected burn wound model. In addition, GT/Ag cryogels degraded in the body within 4 weeks, which alleviated the pain of peeling the dressing from the wound. Therefore, GT/Ag cryogels with outstanding antibacterial properties and effective absorption of wound exudates are excellent candidates for wound dressings to promote burn wound repair.