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AIM:To observe the anti-scarring effects and safety of triamcinolone acetonide(TA)-loaded hydrogel sustained-release sheeting on stab incision glaucoma surgery(SIGS)with “one-step tunnel method” in rabbit eyes.METHODS:A total of 48 healthy New Zealand white rabbits were randomly selected and divided into 4 groups(12 rabbits in each group), trabeculectomy(Trab)group, SIGS group, polyvinyl alcohol hydrogel(PVAH)sheeting was implanted under the conjunctiva flap during SIGS(PVAH group), and hydrogel sustained-release sheeting loaded with TA was implanted under the conjunctiva flap during SIGS(TA/PVAH group). On the 1, 2, 3, and 4 wk after surgery, the intraocular pressure, filtering bubble morphology, anterior chamber reaction, and other complications were observed and recorded in each group. Then animals were euthanized, and the surgery area tissues of right eye were taken for pathological tissue paraffin section. Masson staining, picric acid-Sirius rose red staining, as well as α-smooth muscle actin(α-SMA)and fibroblast growth factor 2(FGF2)immunohistochemistry staining was performed on every section. The infiltration of inflammatory cells, proliferation of fibroblasts and synthesis of type I and type III collagen fibers in local tissues were observed. The average positive area ratio of α-SMA and FGF2 antibody immunohistochemical staining in each group was calculated and compared.RESULTS: The TA/PVAH group maintained diffuse and elevated functional filtering blebs, while flat filtering blebs appeared in Trab, SIGS and PVAH groups at 2 wk after surgery. Functional filtering blebs were present in 1 eye(33%), 2 eyes(67%)in the PVAH and TA/PVAH group at 4 wk after surgery, respectively, while the other filtering blebs were flattened. Masson staining showed that the hydrogels in PVAH and TA/PVAH groups did not degrade at 4 wk after surgery. Compared with the Trab and SIGS groups, the filtration passages were more obvious, with less collagen fiber proliferation. Sirius red staining showed that the expression of type I collagen and type III collagen in the TA/PVAH group was less than that in the Trab group, SIGS group and PVAH group at 4 wk after surgery. Immunohistochemical staining showed that the α-SMA expression in the TA/PVAH group was significantly lower than that in the Trab and SIGS groups at 1 wk after surgery(P<0.01). The α-SMA expression was the highest in the Trab and SIGS groups at 2 wk after surgery, while the α-SMA expression in the PHAP and TA/PVAH groups was significantly lower than that in the first two groups(P<0.01). Compared with the Trab group, the expression of FGF2 in the PVAH and TA/PVAH group was significantly increased at 1, 2, 3 and 4 wk after surgery(P<0.05). Compared with the SIGS group, FGF2 expression in the TA/PVAH group was significantly increased at 4 wk after surgery(P<0.05).CONCLUSION:In SIGS surgery of rabbit eyes, implanting hydrogel sustained-release sheeting loaded with TA under conjunctival flap can effectively inhibit the scarring of the filtering bleb, which may be the interaction of the anti-scar effect of TA and the stent function of hydrogel.
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@#Graphene family nanomaterials (GFNs) are highly popular in the field of bone tissue engineering because of their excellent mechanical properties, biocompatibility, and ability to promote the osteogenic differentiation of stem cells. GFNs play a multifaceted role in promoting the bone regeneration microenvironment. First, GFNs activate the adhesion kinase/extracellularly regulated protein kinase (FAK/ERK) signaling pathway through their own micromorphology and promote the expression of osteogenesis-related genes. Second, GFNs adapt to the mechanical strength of bone tissue, which helps to maintain osseointegration; by adjusting the stiffness of the extracellular matrix, they transmit the mechanical signals of the matrix to the intracellular space with the help of focal adhesions (FAs), thus creating a favorable physiochemical microenvironment. Moreover, they regulate the immune microenvironment at the site of bone defects, thus directing the polarization of macrophages to the M2 type and influencing the secretion of relevant cytokines. GFNs also act as slow-release carriers of bioactive molecules with both angiogenic and antibacterial abilities, thus accelerating the repair process of bone defects. Multiple types of GFNs regulate the bone regeneration microenvironment, including scaffold materials, hydrogels, biofilms, and implantable coatings. Although GFNs have attracted much attention in the field of bone tissue engineering, their application in bone tissue regeneration is still in the basic experimental stage. To promote the clinical application of GFNs, there is a need to provide more sufficient evidence of their biocompatibility, elucidate the mechanism by which they induce the osteogenic differentiation of stem cells, and develop more effective form of applications.
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objective:To prepare a composite photocrosslinked hydrogel containing zeolite imidazole framework-8(ZIF-8),and to evaluate its in vitro cytotoxicity,drug release capability,and antimicrobial propertie.Methods:The ZIF-8 particles were synthesized by hydrothermal method,and the microstructure characteristic was observed under scanning electron microscope(SEM).The particles were mixed with the gelatin methacryloyl(GelMA)with the mass fraction of 0.2%to obtain the composite hydrogel GelMA-Z.The atomic absorption spectroscope was used to detect the cumulative zinc ion(Zn2+)release amounts in GelMA-Z at different time points.The NIH-3T3 cells were co-cultured with GelMA-Z for 1,3,and 7 d;the viabilities of the cells in various groups were detected by CCK-8 assay;the GelMA-Z was co-cultured with Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)for 6,12,and 24 h and divided into control group,GelMA group,and GelMA-Z group.The bacterial activities of the cells in various groups at different time points were detected by microplate reader;the bacterial formation and the presence of live/dead becterial staining condition were detected by plate antibacterial experiment and live/dead bacterial staining method.Results:The SEM observation results showed that the hydrothermally synthesized ZIF-8 particles had the uniform particle sizes.The atomic absorption spectroscope results showed that Zn2+ in GelMA-Z showed an initial burst phase within 1 d,followed by a slow release,and reached the equilibrium around 7 d.Compared with control group,the viabilities the cells in GelMA group and GelMA-Z group were above 90%on the 1st,3rd,and 7th days,but there was no significant difference(P>0.05).The bacterial activity detection results showed that when co-cultured with bacteria for 6,12,and 24 h,compared with control group and GelMA group,the bacterial activities of the E.coli and S.aureus in GelMA-Z group were decreased(P<0.05).The plate antibacterial experiment results showed that the number of bacterial formation in GelMA-Z group was fewer than those in control group and GelMA group.The live/dead bacterial staining results showed that in GelMA-Z group,there was a large number of red fluorescence stained dead bacteria;in control group and GelMA group,there was a large number of green fluorescence stained live bacteria.Conclusion:The GelMA hydrogel loaded with ZIF-8 particles can achieve the in situ photocrosslinking and possesses good Zn2+ release capability and antimicrobial activity,and it is a novel hydrogel dressing for treatment of the infected wounds.
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Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.
摘要
Objective To evaluate the application value of hydrogel in image guided radiotherapy(IGRT)for prostate cancer(PCa).Methods Eighty PCa patients in the First Affiliated Hospital of Hebei North University from October 2022 to February 2023 were collected.The patients were divided into experiment group injected with hydrogel(n=33)and control group without hydrogel(n=47)by central random system allocation.The acute and advanced radiation proctitis(RP)incidence rate of the two groups were compared.Patients in experimental group were divided into RP group(n=5)and non-RP group(n=28).The independent risk factors leading to RP were analyzed by using logistic regression for PCa patients.Results In experiment group,12.1％(4/33)of the patients developed acute grade Ⅰ RP,and 3.0％(1/33)developed advanced grade Ⅰ RP.In control group,31.9％(15/47)of the patients developed acute grade Ⅰ RP,and 12.8％(6/47)developed acute grade Ⅱ RP;19.1％(9/47)of patients developed advanced grade Ⅰ RP,4.3％(2/47)developed advanced grade Ⅱ RP,and 2.1％(1/47)developed advanced grade Ⅲ RP.The incidence of acute and advanced RP in experiment group was lower than that in control group(P<0.05).The application of hydrogel effectively reduced rectal toxicity.Age,rectal volume,V70 and V78 were independent risk factors for the incidence of RP in Pca patients(P<0.05).The characteristics of hydrogel injection were not related to the incidence of RP for Pca patients.Conclusions Hydrogel can effectively reduce the rectal toxicity for Pca patients in IGRT and has little impact on the overall treatment.Hydrogel has certain clinical application and promotion value.
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When skin injuries are healing, complex wound environments can be easily created, which can result in wound infection, excessive inflammation caused by neutrophil accumulation and inflammatory factors, and excessive reactive oxygen species, resulting in high levels of oxidative stress. As a result of these factors, cell membranes, proteins, DNA, etc. may become damaged, which adversely affects the repair function of normal cells around the wound, resulting in the formation of chronic wounds. The effectiveness of wound dressings as a treatment is well known. They can offer temporary skin damage protection, prevent or control wound infection, create an environment that is conducive to mending skin damage, and speed wound healing. Traditional dressings like gauze, cotton balls, and bandages, however, have the drawbacks of having no antimicrobial properties, having weak adhesive properties, having poor mechanical properties, being susceptible to inflammation, obstructing angiogenesis, needing frequent replacement, and being unable to create an environment that is conducive to wound healing. As an innovative bandage, self-assembled hydrogel has great water absorption, high water retention, superior biocompatibility, biodegradability and three-dimensional (3D) structure. With properties including hemostasis, antibacterial, anti-inflammatory, and antioxidant, the synthesized raw material itself and the loaded active compounds have a wide range of potential applications in the treatment of skin injuries and wound healing. This research begins by examining and discussing the mechanism of cross-linking in self-assembled hydrogels. The cross-linking modes include non-covalent consisting of physical interaction forces such as electrostatic interactions, π-stacking, van der Waals forces, hydrophobic interactions, and metal-ligand bonds, covalent cross-linking formed by dynamic covalent bonding such as disulfide bonding and Schiff bases. And hybrid cross-linking with mixed physical forces and dynamic covalent bonding. The next part describes the special structure and excellent functions of self-assembled hydrogels, which include an extracellular matrix-like structure, the removal of exogenous microorganisms, and the mitigation of inflammation and oxidative stress. It goes on to explain the benefits of using self-assembled hydrogels as dressings for skin injuries. These dressings are capable of controlling cell proliferation, loading active ingredients, achieving hemostasis and coagulation, hastening wound healing, and controlling the regeneration of the injured area. The development of self-assembly hydrogels as dressings is summarized in the last section. The transition from purely non-covalent or covalent cross-linking to hybrid cross-linking with multiple networks, from one-strategy action to multi-strategy synergy in exerting antimicrobial, anti-inflammatory, and antioxidant effects and from single-function to multi-functioning in a single product. Additionally, it is predicted that future developments in self-assembled hydrogels will focus on creating biomimetic gels with multi-strategy associations linkage from naturally self-assembling biomolecules peptides, lipids, proteins and polysaccharides; improving the properties and cross-linking of raw materials to enhance the storage capabilities of hydrogels and cross-linking techniques, realizing the recycling of hydrogels; conducting additional research and exploration into the cross-linking process of hydrogels; and realizing the gel’s controllable rate of degradation. Furthermore, combining 3D printing and 3D microscopic imaging technology to design and build one-to-one specialized gel dressings; using computer simulation and virtual reality to eliminate the time factor, resulting in self-assembled hydrogels that perfectly fit the ideal dressing.
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Objective@#To investigate the osteogenic properties of a methacrylated gelatin (GelMA) / bone marrow mesenchymal stem cells (BMSCs) composite hydrogel applied to the skull defect area of rats and to provide an experimental basis for the development of bone regeneration biomaterials.@*Methods@#This study was approved by the Animal Ethics Committee of Nanjing University. A novel photocurable composite biohydrogel was developed by constructing photoinitiators [lthium phenyl (2,4,6-trimethylbenzoyl) phosphinate, LAP], GelMA, and BMSCs. The surface morphology and elemental composition of the gel were examined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The compressive strength of the gel was evaluated using an electronic universal testing machine. After in vitro culture for 1, 2, and 5 days, the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay, and their survival and morphology were examined through confocal microscopy. A 5 mm critical bone deficiency model was generated in a rat skull. The group receiving composite hydrogel treatment was referred to as the GelMA/BMSCs group, whereas the untreated group served as the control group. At the 4th and 8th weeks, micro-CT scans were taken to measure the bone defect area and new bone index, while at the 8th week, skull samples from the defect area were subjected to H&E staining, van Gieson staining, and Goldner staining to evaluate the quality of bone regeneration and new bone formation.@*Results@#SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology, the porosity of GelMA was 73.41% and the pore size of GelMA was (28.75 ± 7.13) μm. EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel. The hydrogel compression strength was 152 kPa. On the 5th day of GelMA/BMSCs culture, the cellular morphology transitioned from oval to spindle shaped under microscopic observation, accompanied by a significant increase in cell proliferation (159.4%, as determined by the CCK-8 assay). At 4 weeks after surgery, a 3D reconstructed micro-CT image revealed a minimal reduction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group. At 8 weeks after surgery, no significant changes were observed in the control group's bone defect area, with only limited evidence of new bone growth; however, substantial healing of skull defects was evident in the GelMA/BMSCs group. Quantitative analysis at both the 4- and 8-week examinations indicated significant improvements in the new bone volume (BV), new bone volume/total bone volume (BV/TV), bone surface (BS), and bone surface/total bone volume (BS/TV) in the GelMA/BMSCs group compared to those in the control group (P<0.05). Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone, primarily consisting of fibrous connective tissue, at the defect edge in the control group.@*Conclusion@#Photocuring hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.
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BACKGROUND:A large number of studies have confirmed that exosomes can promote osteogenesis and vascularization.However,simple exosome therapy has problems such as poor targeting,and the content of loaded molecules cannot reach the therapeutic concentration. OBJECTIVE:To load exosomes into injectable gluconolactone-sodium alginate β-tricalcium phosphate-polyethylene glycol hydrogel,and observe the effect of the hydrogel on peri-implant bone defect in vivo and in vitro. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells and wrapped in injectable gluconolactone-sodium alginate β-tricalcium phosphate-polyethylene glycol hydrogel.(1)In vitro experiment:The hydrogel loaded with exosomes and the hydrogel without exosomes were cocultured with endothelial progenitor cells,and exosomes uptake experiment,tubule formation experiment,cell proliferation,migration ability,and angiogenic gene detection were carried out.(2)In vivo experiment:Twelve male New Zealand white rabbits were used to prepare two standard implant cavities and corresponding bone defects in the long axis of one femur.A hydrogel loaded with exosomes was implanted in the bone defect after an implant was implanted in a cavity at the proximal end of the implant(experimental group),and an unloaded exosome hydrogel was implanted in the bone defect after an implant was implanted in a cavity at the distal end of the implant(control group).At 3,6 and 9 weeks after operation,bone defects with implants were removed and stained with hematoxylin-eosin staining and Masson staining.Simultaneously,osteogenic and angiogenic genes were detected at 9 weeks after operation. RESULTS AND CONCLUSION:(1)In vitro experiment:Exosomes could enter endothelial progenitor cells.The proliferation,migration,angiogenesis and gene(CD31,vascular endothelial growth factor and basic fibroblast growth factor)expression of endothelial progenitor cells in the hydrogel-loaded group were higher than those in the hydrogel-unloaded group(P<0.05).(2)In vivo experiment:Hematoxylin-eosin staining and Masson staining showed that at 3 weeks after operation,only a small amount of new bone was found in the two groups,and the material was partially degraded.At 6 weeks after operation,the amount of new bone in the two groups increased,and a large amount of new bone was found in the experimental group,with obvious calcium deposition.At 9 weeks after operation,compared with the control group,a large number of bone trabeculae thicker than mature were found in the experimental group,calcium salt deposition was more obvious,and a large number of osteoblasts were found around the bone trabeculae.The protein expressions of CD31,vascular endothelial growth factor,basic fibroblast growth factor,bone morphogenetic protein 2,type I collagen and osteocalcin in the experimental group were higher than those in the control group at 9 weeks after operation(P<0.05).(3)The exosome-loaded gluconolactone-sodium alginate β-tricalcium phosphate-polyethylene glycol hydrogel could promote the proliferation,migration and angiogenic differentiation of endothelial progenitor cells and promote the repair and regeneration of bone defects around implants.
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BACKGROUND:Salvianolic acid B can inhibit cell damage induced by H2O2,effectively remove excess reactive oxygen species,and exert antioxidant properties.It has been used in the treatment of many diseases.However,there are relatively few studies on the role and mechanism of salvianolic acid B in intervertebral disc degeneration. OBJECTIVE:To observe the effect and mechanism of salvianolic acid B on oxidative stress-induced intervertebral disc degeneration by using gelatin methacryloyl hydrogel as a carrier through the in vitro cell experiment and the in vivo animal experiment. METHODS:The gelatin methacryloyl hydrogel(drug-loaded hydrogel)loaded with salvianolic acid B was prepared.(1)In vitro cell experiment:The lumbar nucleus pulposus cells of adult SD rats were isolated and extracted,and passage 3 nucleus pulposus cells were selected and divided into groups:Group A was added complete medium.In group B,a complete medium containing H2O2 was added.Group C was inoculated on methylacrylylated gelatin hydrogel and added with a complete medium containing H2O2.Group D was inoculated on methyl acrylyl gelatin hydrogel loaded with salvianolic acid B and added into a complete medium containing H2O2.The E group was inoculated on the methylacrylyl gelatin hydrogel loaded with salvianolic acid B,and the complete medium containing H2O2 and the complete medium containing TLR4 signaling pathway inhibitor were added.Cell proliferation,oxidative stress,inflammatory response,gene expression of cell matrix-associated proteins and the protein expression of TLR4/nuclear factor-kB signaling pathway were detected.(2)Animal in vivo experiment:Sixty adult SD rats were randomly divided into normal group,acupuncture group,acupuncture + salvianolic acid group,acupuncture + hydrogel group and acupuncture + loading potion gel group,with 12 rats in each group.The last four groups were treated with acupuncture to establish models of intervertebral disc degeneration and then injected with normal saline,salvianolic acid B solution,non-drug loaded gel and drug-loaded gel in turn.Imaging examination and pathological observation were performed 4 weeks after surgery. RESULTS AND CONCLUSION:(1)In vitro cell experiment:Compared with group A,the cell proliferation was decreased;the oxidative stress reaction and inflammation reaction were enhanced;the expression of extracellular matrix degrading enzymes(matrix metalloproteinase 3,matrix metalloproteinase 13,ADAMTS4,ADAMTS5)was increased in group B(P<0.05),and the synthesis of extracellular matrix(type Ⅱ collagen,proteoglycan)was decreased(P<0.05).The protein expression of the TLR4/nuclear factor-kB signaling pathway was increased(P<0.05).Compared with group B,the cell proliferation of groups D and E was increased,the oxidative stress response and inflammatory response were weakened,and the expression of extracellular matrix degrading enzymes(matrix metalloproteinase 3,matrix metalloproteinase 13,ADAMTS4,ADAMTS5)was decreased(P<0.05),and the synthesis of extracellular matrix was increased(P<0.05).The protein expression of TLR4/nuclear factor-kB signaling pathway was decreased(P<0.05),and the effect was more significant in group E.(2)Animal in vivo experiment:4 weeks after surgery,intervertebral disc height index,index of MRI and pathological and histological grading of the intervertebral disc had improved significantly in the acupuncture+drug-loaded hydrogel group,and simply injecting hydrogel or salvianolic acid B solution can to a certain extent improve the intervertebral disc degeneration,but they are not as good as the injection of the drug-loaded hydrogel.(3)It is concluded that gelatin methacryloyl hydrogel loaded with salvianolic acid B can inhibit oxidative stress and inflammation in the degenerated intervertebral disc tissue,inhibit the degradation of extracellular matrix,and alleviate the process of intervertebral disc degeneration,which may be accomplished by inhibiting the TLR4/nuclear factor-kB signaling pathway.
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BACKGROUND:Medical hydrogels are new functional polymer materials with three-dimensional structural networks and excellent biocompatibility,which have been widely studied in the field of tissue engineering and drug carriers,but the research on the combination of medical hydrogels and Chinese medicine for the treatment of diseases based on tissue engineering is still in the early exploration stage.Therefore,through the analysis of the mechanism of the role of medical hydrogels,the integration of medical hydrogels and Chinese medicine in the research of the joint application of the article,can better provide ideas for scientific researchers,and the joint application of Chinese medicine and medical hydrogels is of great significance. OBJECTIVE:To explore the strategy and significance of Chinese medicine combined with medical hydrogel for disease treatment based on tissue engineering research. METHODS:PubMed and CNKI were used to retrieve articles about the application of Chinese medicine combined with medical hydrogel in tissue engineering from January 2010 to November 2022,with the Chinese and English search terms"hydrogel,traditional Chinese medicine,drug carrier,tissue engineering".After the initial screening of all articles according to the inclusion and exclusion criteria,the 61 articles with high relevance were retained for review. RESULTS AND CONCLUSION:(1)Although the application of Chinese medicine combined with medical hydrogel is involved in intra-articular,intra-tissue organ,soft tissue wounds,tissue engineering,etc.,except for the clinical application of Chinese medicine combined with hydrogel dressing for soft tissue injury,other aspects are still in the experimental stage.(2)The development of Chinese medicine combined with medical hydrogel has great potential and development prospects,but there is a certain difficulty in the manufacture of the gel with high-performance requirements,and it is difficult to master the physical and chemical properties precisely.(3)At present,the comprehensive view of injectable hydrogel with the characteristics of easy to use,its joint use of Chinese medicine can be extended to a wider range,can be used for joint,organ,tissue engineering-related disease treatment.Smart hydrogel has high sensitivity and reversible transformation can also meet the use of the special environment.During the combined use of Chinese medicine,it also needs to understand the mechanism of action of Chinese medicine components.(4)The strategy of combining Chinese medicine with medical hydrogels for disease treatment should start with matching the therapeutic effects of Chinese medicine on organs,tissues and cells combined with appropriate types of medical hydrogels to make up for the shortcomings of traditional Chinese medicine delivery methods and frequent drug delivery.In tissue engineering,hydrogels can be loaded with stem cells after Chinese medicine intervention,or with both Chinese medicine and stem cells for disease treatment.(5)In future research of combined Chinese medicine and medical hydrogel application,we also need to consider:we should ensure that the biological properties of medical hydrogel can be quantified,and grasp the characteristics of hydrogel with different manufacturing processes of different materials to produce the required medical hydrogel that meets the application conditions.In Chinese medicine,we need to comprehensively understand and analyze the therapeutic effects and application mechanisms of known Chinese medicine monomer and Chinese medicine compound extracts,so as to achieve a more perfect combination between Chinese medicine and medical hydrogel under a more clear mechanism.With the continuous improvement of medical science and technology innovation,the medical hydrogel can be innovatively combined with other traditional treatment methods of Chinese medicine,such as acupuncture,massage,cupping and so on,to be used from multiple angles.
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BACKGROUND:Magnetically responsive hydrogels have great advantages in bone tissue engineering,which is more conducive to the minimally invasive and efficient promotion of osteogenesis. OBJECTIVE:To review the application advances of magnetically responsive hydrogels in bone tissue engineering. METHODS:PubMed,Web of Science,WanFang and CNKI databases were used to search relevant literature.The English search terms were"Magnetic Hydrogels,Magnetic Nanoparticles,Superparamagnetic Nanoparticles,Fe3O4,SPIONs,Magnetic Fields,Bone Regeneration,Bone Repair,Bone Tissue Engineering".The Chinese search terms were"Magnetic Hydrogel,Magnetic Nanoparticles,Superparamagnetic Iron Oxide Nanoparticles,Magnetic Field,Iron Oxide Nanoparticles,Bone Regeneration,Bone Reconstruction,Bone Repair,Bone Tissue Engineering".After preliminary screening of all articles according to the inclusion and exclusion criteria,60 articles were finally retained for review. RESULTS AND CONCLUSION:(1)In recent years,due to the emergence of magnetic nanoparticles,more and more magnetic responsive scaffold materials have been developed.Among them,magnetic responsive hydrogels containing iron oxide nanoparticles and superparamagnetic iron oxide nanoparticles have outstanding mechanical properties and good biocompatibility.It can quickly respond to the external magnetic field and provide the magnetic-mechanical signals needed for seed cells to form bone.(2)Magnetic-responsive hydrogel can be used as a carrier to accurately regulate the release time of growth factors.(3)Under the three-dimensional microenvironment culture platform based on magnetically responsive hydrogel,the magnetic force at the interface between the magnetic response hydrogel and cells can activate cell surface sensitive receptors,enhance cell activity,and promote the integration of new bone and host bone.(4)The injectable magnetically responsive hydrogel can be used in the field of magnetic hyperthermia and biological imaging of bone tumors.(5)At present,magnetically responsive hydrogels are expected to mimic the anisotropic layered structure observed in natural bone tissue.However,most of the studies on magnetically responsive hydrogels focus on in vitro studies,and the mechanism of interaction between magnetically responsive hydrogels and the local microenvironment in vivo is still insufficient.(6)Therefore,based on the successful application of magnetic nanoparticles in magnetic resonance imaging,it is expected to optimize the properties of magnetic nanoparticles in the future to construct magnetic responsive hydrogels with suitable degradation properties,mechanical properties,and vascular functionalization,which can monitor changes in vivo in real time.
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BACKGROUND:Hydrogel microparticles,due to their porous and injectable properties,have demonstrated unique advantages in biomedical fields,such as the delivery of cells and bioactive factors/drugs,the construction of tissue repair scaffolds.They have broad application prospects. OBJECTIVE:To review the latest research progress and discuss the key problems and challenges in the research of bone tissue engineering based on hydrogel microparticles. METHODS:The relevant articles in PubMed and CNKI were searched by computer.The English key words were"hydrogels,microparticles,microspheres,microcarriers,bone,bone defect,bone repair,bone healing,bone tissue engineering"while the Chinese key words were"hydrogels,microparticles,microspheres,bone tissue engineering,bone defect,bone repair,bone regeneration".The retrieval period was from 2002 to 2022,and 127 articles were finally included for review. RESULTS AND CONCLUSION:(1)At present,various hydrogel microparticles have been developed for use in bone tissue engineering strategies,for example,hydrogel microparticles carrying cells or bioactive factors/drugs,hydrogel microparticles as biological scaffolds,stimulus-responsive hydrogel microparticles,biomineralized hydrogel microparticles,hydrogel microparticles combined with other biological materials.(2)Bone tissue engineering repair strategies based on hydrogel microparticles mainly regulate bone repair by promoting stem cell recruitment and osteogenic differentiation,regulating the local inflammatory microenvironment and promoting angiogenesis at the site of injury.However,the present studies did not deeply explore the effect of bone tissue engineering based on hydrogel microparticles on the recruitment and differentiation of endogenous stem cells and the regulation of the inflammatory microenvironment by the physical and chemical properties of hydrogel microparticles.The long-term in vivo adverse reactions of hydrogel microparticles have not been explored yet,and it is difficult to mass-produce them,thus future research needs to strengthen the mechanism exploration and technical route,so as to provide a reasonable reference for the development of hydrogel microparticles that can be used for clinical transformation.
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BACKGROUND:Near infrared responsive hydrogels,have a variety of excellent properties such as high spatial and temporal precision,remote tunability,and safety and non-invasiveness,providing a new direction of exploration for the development of tissue engineering. OBJECTIVE:To summarize the application progress of near infrared responsive hydrogels in the field of tissue engineering in recent years. METHODS:The literature search was performed on PubMed and CNKI databases.The keywords were"near infrared responsive hydrogels,tissue engineering,bone defect,bone repair,bone regeneration,wound healing,wound dressing,angiogenesis"in Chinese and English.The search time limit was from May 2006 to October 2022 and extended for some classical literature.The abstracts and contents of the retrieved literature were analyzed,and the relevant literature was obtained according to inclusion and exclusion criteria.Finally,97 articles were included for review. RESULTS AND CONCLUSION:(1)Near infrared responsive materials are involved in tissue repair by controlling infection and reducing inflammation,promoting angiogenesis,osteoblast differentiation and new bone formation.(2)Near infrared responsive hydrogel can be prepared by constructing a thermosensitive hydrogel with a photothermal effect or by using a photochemical reaction.(3)Near infrared responsive hydrogels as wound dressings perform various functions such as rapid hemostasis,tissue adhesion through polymerization of polymer monomers,antibacterial and anti-inflammatory effects,and promotion of angiopoiesis and epithelial regeneration through the local photothermal effect of photothermal nanomaterials during soft tissue healing and regeneration.(4)Near infrared responsive hydrogels function during bone reconstruction and repair by promoting osteogenic differentiation of mesenchymal stem cells,stimulating the expression of heat shock proteins,and increasing angiogenesis.(5)Near infrared responsive hydrogels present a combination of multiple therapeutic strategies with significant synergistic therapeutic functions and are also being progressively developed for application in other tissue reconstruction and disease treatment scenarios.
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BACKGROUND:Osteochondral defect of the joint is a difficult problem faced by orthopedic surgeons,and traditional repair methods are difficult to obtain satisfactory curative effects.Hydroxyapatite-polyvinyl alcohol-based composite hydrogel material is a direction of current research. OBJECTIVE:To prepare hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel material and characterize its physical characteristics,to verify its histocompatibility and cell adhesion and proliferation ability after implantation in vivo,and explore its repair effect on rabbit osteochondral defects. METHODS:The cylindrical porous poly(lactic acid)scaffold was prepared by 3D printing technology(the pore sizes were 1.2,1.4,1.6 and 1.8 mm,respectively).The poly(lactic acid)scaffold was injected with polyvinyl alcohol and hydroxyapatite mixed emulsion.After freezing thawing and dichloromethane dissolution,hydroxyapatite-polyvinyl alcohol hydrogel was prepared.Then,the collagen-chitosan-gelatin mixture was injected into the hydroxyapatite-polyvinyl alcohol hydrogel and crosslinked with genipin.Finally,the hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel was prepared by alcohol cleaning and freeze-drying.The physical characteristics of the four groups of hydrogels were characterized,and the hydrogels with the best performance were screened for follow-up experiments.Hydroxyapatite-polyvinyl alcohol hydrogel and collagen-chitosan-gelatin composite hydrogel were implanted subcutaneously in SD rats.Hematoxylin-eosin staining and Masson staining were used to observe the adhesion growth of cells on the material surface.Osteochondral defect(diameter:5 mm,depth:6 mm)models were made in the femoral trochlea of bilateral knee joints of 15 rabbits.The composite hydrogel was implanted on the left side(experimental group),while no material was implanted on the right side(control group).Micro-CT and histology were used to evaluate the repair effect of osteochondral defects. RESULTS AND CONCLUSION:(1)Based on the results of porosity,water content,mechanical testing and scanning electron microscopy,it was concluded that the hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel with a pore size of 1.2 mm was more consistent with the general characteristics of natural cartilage,which was used for subsequent experiments.(2)Hematoxylin-eosin staining and Masson staining exhibited that with the extension of subcutaneous implantation time of the materials,the adhesion of cells around the two materials increased significantly,and the proliferation of cells after the implantation of collagen-chitosan-gelatin was better,a large number of cells could be seen growing into the formed network structure,and the network structure was gradually degraded.(3)In the rabbit osteochondral defect experiment,8 weeks after surgery,Micro-CT examination demonstrated that the material implanted in the experimental group had good integration with the surrounding bone-cartilage,with some bone growth on the surface and inside,while the cartilage and subcartilage in the control group still had obvious defects,without effective repair.Hematoxylin-eosin staining and toluidine blue staining displayed that the composite hydrogel in the experimental group integrated with the surrounding articular cartilage 4-8 weeks after implantation.With the extension of time,new cartilage gradually formed on the surface of the material.At 12 weeks,most of the defect was covered by new cartilage,and good bone growth was also observed in the subcartilage.In the control group,the deep bone defects were mostly repaired and the superficial cartilage and subchondral bone defects were also repaired to a certain extent,but they were mainly replaced by fibrous tissue and part of fibrocartilage 12 weeks after surgery.(4)In conclusion,hydroxyapatite-polyvinyl alcohol/collagen-chitosan-gelatin composite hydrogel material can mimic the structure and function of natural cartilage,and can effectively repair osteochondral defects in animal experiments.
摘要
BACKGROUND:Diabetic wounds have complicated conditions such as infection,ischemia,peripheral neuropathy,and vascular disease.Ordinary hydrogel dressings with single structure and function cannot meet the needs of diabetic wound healing. OBJECTIVE:To explore the effect of a hydrogel loaded with platelet-rich plasma on wound healing of full-thickness skin defects in diabetic rats. METHODS:The blood of SD rats was extracted to prepare platelet-rich plasma.Carboxymethyl chitosan/oxychondroitin sulfate hydrogel and carboxymethyl chitosan/oxychondroitin sulfate hydrogel loaded with platelet-rich plasma were prepared separately.Streptozotocin was used to induce diabetes model in adult male SD rats.A round full-thickness skin wound with a diameter of 2 cm was made on the back of diabetic rats.The rats were randomly divided into four groups(n=10 per group).The blank group was applied with gauze on the wound.The hydrogel group,platelet-rich plasma group,and composite hydrogel group were respectively applied with the corresponding hydrogel,platelet-rich plasma and hydrogel loaded with platelet-rich plasma.The wound healing was observed within 20 days after treatment. RESULTS AND CONCLUSION:(1)On day 20 after treatment,the wound healing rate of the hydrogel group,platelet-rich plasma group and composite hydrogel group was significantly higher than that of the blank group(P<0.05).The wound healing rate of the composite hydrogel group was significantly higher than that of the platelet-rich plasma group(P<0.05).(2)The results of hematoxylin-eosin staining on day 5 after treatment showed that compared with the blank group,hydrogel group and platelet-rich plasma group,there were a large number of inflammatory cell infiltration,new granulation tissue and capillary formation in the wound tissue of the composite hydrogel group.(3)On day 5 after treatment,the results of immunohistochemical staining and western blot assay showed that the expression levels of tumor necrosis factor α and interleukin 1β in wound tissue in the composite hydrogel group were significantly lower than those in the blank group,hydrogel group and platelet-rich plasma group(P<0.05).(4)Masson staining results on day 15 after treatment showed that compared with the blank group,hydrogel group and platelet-rich plasma group,there were more collagen fibers in the wound tissue of the composite hydrogel group,which were orderly,evenly distributed and dense.(5)CD31 immunofluorescence staining showed that on day 15 after treatment,the expression of CD31 in wound tissue of the composite hydrogel group was significantly higher than that of the blank group,hydrogel group and platelet-rich plasma group(P<0.05).(6)These results suggest that the hydrogel loaded with platelet-rich plasma can promote the healing of full-thickness skin defect wounds in diabetic rats by promoting granulation tissue,collagen fiber and angiogenesis,and reducing the inflammatory response.
摘要
BACKGROUND:For the replacement treatment of long-segment tracheal defects,although tissue engineering research has made some progress in recent years,it is still not perfect,and one of the biggest difficulties is that the hemodynamic reconstruction of the tracheal replacement cannot be achieved rapidly. OBJECTIVE:To preliminarily explore the potential of polycaprolactone scaffolds modified with exosome-loaded hydrogels to construct a rapidly vascularized tracheal substitute. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells of SD rats.After preparation of hyaluronic acid methacrylate solution,the exosome solution was mixed with hyaluronic acid methacrylate solution at a volume ratio of 1:1.Hyaluronic acid methacrylate hydrogels loaded with exosomes were prepared under ultraviolet irradiation for 5 minutes.The degradation of exosome-unloaded hydrogels and the controlled release of exosome-loaded hydrogels were detected.Polycaprolactone scaffolds were prepared by 3D printing.The pure hyaluronic acid methacrylate solution and the exosome-loaded hyaluronic acid methacrylate solution were respectively added to the surface of the scaffold.Hydrogel-modified scaffolds and exosome-modified scaffolds were obtained after ultraviolet irradiation.Thirty SD rats were randomly divided into three groups with 10 rats in each group and subcutaneously implanted with simple scaffolds,hydrogel-modified scaffolds and exosome-modified scaffolds,respectively.At 30 days after surgery,the scaffolds and surrounding tissues of each group were removed.Neovascularization was observed by hematoxylin-eosin staining and Masson staining and the expression of CD31 was detected by immunofluorescence. RESULTS AND CONCLUSION:(1)As time went by,the hydrogel degraded gradually,and the exosomes enclosed in the hydrogel were gradually released,which could be sustained for more than 30 days.The exosome release rate was faster than the degradation rate of the hydrogel itself,and nearly 20%of the exosomes were still not released after 30 days of soaking.(2)Under a scanning electron microscope,the surface of the simple polycaprolactone scaffold was rough.After hydrogel modification,a layer of gel was covered between the pores of the scaffold,and the scaffold surface became smooth and dense.(3)After 30 days of subcutaneous embedding,hematoxylin-eosin staining and Masson staining showed that more neovascularization was observed inside the scaffolds of the exosome-modified scaffold group compared with the hydrogel-modified scaffold group.The hydrogels on the scaffolds of the two groups were not completely degraded.Immunofluorescence staining showed that CD31 expression in the exosome-modified scaffold group was higher than that in the hydrogel-modified scaffold group(P<0.000 1).(4)These results indicate that hyaluronic acid methacrylate hydrogels can be used as controlled-release carriers for exosomes.The 3D-printed polycaprolactone scaffold modified by hyaluronic acid methacrylate hydrogel loaded with exosomes has good biocompatibility and has the potential to promote the formation of neovascularization.
摘要
BACKGROUND:At present,nanocomposite gelatin methacryloyl hydrogels have been extensively studied in bone tissue engineering. OBJECTIVE:To review the latest research progress of nanocomposite gelatin methacryloyl hydrogels,and introduce the application of nanocomposite gelatin methacryloyl hydrogels in different bone defect environments. METHODS:The computer retrieval was conducted for relevant literature published in CNKI,WanFang,PubMed,and Web of Science databases from 2016 to 2023.The Chinese and English search terms were"gelatin,methacryl*,nano*,bone,bone tissue engineering,bone regeneration,osteogenesis". RESULTS AND CONCLUSION:(1)Up to now,inorganic nanomaterials,organic nanomaterials and organic-inorganic hybrid nanomaterials are the main nanomaterials used as fillers for gelatin methacryloyl.(2)Inorganic nanomaterials enhance the mechanical strength of gelatin methacryloyl,improve its thixotropic properties and degradation rate,and realize the antibacterial,osteogenic,immunoregulatory,angiogenic and other functions of gelatin methacryloyl hydrogel through its surface charge regulation,drug/factor loading,metal ion self-degradation release,etc.(3)Organic nanomaterial and organic-inorganic hybrid nanomaterial composite gelatin methacryloyl hydrogel are two emerging materials.At present,there are relatively few studies,but from the published research,compared with inorganic nanomaterial gelatin methacryloyl hydrogel,organic nanomaterial gelatin methacryloyl hydrogel has better biocompatibility and drug-loading performance.The interaction between nano phase and organic polymer phase is stronger,and the dispersion of nano particles is better.(4)Organic-inorganic hybrid nanomaterial composite gelatin methacryloyl combines the advantages of the previous two,and has better controllability of metal ion release,which proves great research potential.(5)Nanomaterials can enhance the antibacterial,immune regulation,osteogenesis and other biological properties of gelatin methacryloyl,so as to promote bone regeneration in the complex bone defect microenvironment,such as infected bone defect,diabetes,osteosarcoma resection and so on.However,the relevant research of nanocomposite gelatin methacryloyl hydrogel in bone repair is still limited to animal experiments.Further safety testing and clinical studies are still needed.
摘要
BACKGROUND:Sodium alginate,a natural polysaccharide,has become one of the ideal materials for preparing injectable hydrogels because it is an abundant and cheap resource,and has good biocompatibility and biodegradability.It has been widely used in the production of injectable hydrogels. OBJECTIVE:To review the properties of sodium alginate,the preparation of injectable sodium alginate hydrogel,and its application progress in tissue engineering. METHODS:Web of Science,PubMed,and CNKI were searched by computer.Chinese search terms were"sodium alginate;hydrogel;injectable",and English search terms were"alginate;hydrogel;inject".The time range of searching literature was mainly from June 2017 to June 2022. RESULTS AND CONCLUSION:Alginic acid comes from a wide range of sources,and there are many modifiable groups in its molecular structure,so many injectable hydrogels with excellent properties can be produced by various chemical crosslinking or physical crosslinking methods.Introducing other bioactive molecules or drugs into sodium alginate gel can adjust its properties and broaden its application fields.In addition,injectable sodium alginate hydrogels have great application prospects in biomedicine because of their good biocompatibility,biodegradability and other physical and chemical properties.Sodium alginate hydrogels are evenly mixed with various drugs,cells,factors or other biological molecules in vitro,and can form gels in the human body,which plays a pivotal role in gene carrier,cell scaffold and wound repair.
摘要
BACKGROUND:Clinical skin wound healing continues to be a significant concern,and tissue repair research has moved to the forefront with the development of biomaterials with immunomodulatory properties.Therefore,it is crucial to research wound dressings that have immunomodulatory properties. OBJECTIVE:To prepare chitosan hydrogels that have been modified by arginine with different configurations and assess their capacity to speed up wound healing in a rat animal model. METHODS:(1)In vitro trial:Chitosan modified by pure L-arginine,pure D-arginine,and L-arginine and D-arginine was synthesized by EDC/NHS system,which was then crosslinked with aldehyde-modified four-arm polyethylene glycol.Different chitosan-based hydrogels(CS-L,CS-D,and CS-DL)were finally formed via the Schiff base reaction.Three kinds of hydrogel extracts were co-cultured with fibroblasts respectively.Hydrogel cytocompatibility was assessed using the CCK-8 assay and live/dead staining.The effect of hydrogel on the migration capacity of fibroblasts was assessed by using a scratch test.Three kinds of hydrogels were incubated with rat erythrocyte suspension respectively to evaluate the hemocompatibility of the hydrogels.The hydrogel extract was co-cultured with RAW264.7 macrophages to test the hydrogels'capacity to enhance macrophage NO generation and polarize macrophage phenotype.(2)In vivo experiment:A total of 36 adult SD rats were divided into 4 groups with 9 rats in each group by the random number table method.Two full-layer skin defect wounds of 2 cm×2 cm were made on the back of each rat.Normal saline was added to the wounds of the control group,and corresponding hydrogel was added to the wounds of the CS-L,CS-D,and CS-DL groups,respectively,and then bandaged and fixed.The wound healing was observed regularly after operation.Hematoxylin-eosin staining was performed at 3,10,and 21 days after operation.The samples were collected 10 days after operation and M2 macrophage immunofluorescence staining was performed. RESULTS AND CONCLUSION:(1)In vitro experiments:Under scanning electron microscopy,the three kinds of hydrogels exhibited obvious interpenetrating network structures with pore sizes ranging from 70-200 μm.The three kinds of hydrogels have good swelling performance,degradation performance,self-healing performance,and suitable mechanical strength.The three kinds of hydrogels had good cytocompatibility and hemocompatibility and could promote the migration of fibroblasts.All three kinds of hydrogels had the ability to promote the polarization of macrophages,and CS-D hydrogels had the strongest ability to promote the polarization of macrophages.CS-L hydrogel could significantly promote the production of NO in macrophages.(2)In vivo experiment:3 and 10 days after operation,the wound healing rate in the CS-L and CS-D groups was higher than that in the control group(P<0.05).After 21 days,the wound healing rate of the three hydrogel groups was higher than that of the control group.Hematoxylin-eosin staining displayed that a large number of inflammatory cells were infiltrated in the wound tissue of rats in all groups,accompanied by neovessels and fibroblasts 3 days after operation.10 days after operation,there was still more inflammatory cell infiltration in the wound of the control group,and the inflammation of the other three groups was improved,especially the decrease of inflammatory cells in the CS-D group was more obvious.21 days after operation,the wound epithelium of each group was well repaired,and there was basically no inflammatory cell infiltration in the CS-L and CS-D groups,while there was still a small amount of inflammatory cell infiltration in the control group.Immunofluorescence staining revealed that the number of M2-type macrophages in the CS-D group was higher than that in the other three groups(P<0.05).(3)The results conclude that chitosan hydrogels modified by different configurations of arginine can promote wound healing through different mechanisms.
摘要
BACKGROUND:Based on the concept of the combination of medicine and industry and the advantages of traditional Chinese medicine treatment,the construction of a new composite material loaded with the effective active ingredient of traditional Chinese medicine is a hot research spot in the repair of spinal cord injury,and is expected to become an effective means to solve this problem. OBJECTIVE:To observe the effect of supramolecular conducting hydrogel carrying ligustrazine in repairing spinal cord injury in rats. METHODS:The supramolecular conducting hydrogel carrying ligustrazine was prepared and its microstructure,conductivity,rheology,swelling rate and in vitro release performance were characterized.45 SD rats were divided into 3 groups by random number table method,with 15 rats in each group:no spinal cord injury in the sham operation group;spinal cord injury model was established in the model group;and supramolecular conducting hydrogel carrying ligustrazine was injected into the spinal cord injury area after model establishment in hydrogel group.BBB score was used to evaluate the recovery of hind limb motor function of each group before and 1,7,14,21 and 28 days after modeling,respectively.28 days after the model establishment,the spinal cord tissues were collected and analyzed by hematoxylin-eosin staining,immunohistochemical staining and western blot assay. RESULTS AND CONCLUSION:(1)Under scanning electron microscopy,the supramolecular conducting hydrogel with ligustrazine displayed a three-dimensional micrometer-scale porous network structure with high porosity and a pore size of approximately 100 μm.The conductivity of the hydrogel was 7.66 S/m;the swelling rate was 3 764.42%,and it had certain mechanical stability and injection property.In vitro sustained release experiments demonstrated that the supramolecular conducting hydrogel with ligustrazine sustainably released ligustrazine for more than 800 hours.With the extension of time,the cumulative release of ligustrazine exhibited an increasing trend.(2)With the extension of modeling time,the hind limb motor function gradually recovered in the model group and the hydrogel group,and the hind limb motor function of the hydrogel group was better than that of the model group on 14,21,and 28 days after modeling(P<0.05).Hematoxylin-eosin staining demonstrated that the spinal cord tissue of the model group had cavities and a large number of inflammatory cells could be seen at the stump.In the hydrogel group,some inflammatory cells were infiltrated in the injured area of the spinal cord;the void area of the injured area was reduced;neuron cells appeared in the junction area,and the tissue arrangement was relatively neat.Immunohistochemical staining and western blot assay exhibited that the expression of tumor necrosis factor α and interleukin-6 protein in the rat spinal cord of the hydrogel group was lower than that in the model group(P<0.05),and the expression of neuronal nuclear antigen protein was higher than that in the model group(P<0.05).(3)These findings confirm that the supramolecular conducting hydrogel carrying ligustrazine can promote the repair of spinal cord injury.