Reconstruction of rat calvarial defects utilizing an ultraviolet-cured hydrogel loaded with bone marrow mesenchymal stem cells / 口腔疾病防治

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.

Study on injectable chitosan hydrogel with tendon-derived stem cells for enhancing rotator cuff tendon-to-bone healing / 中国修复重建外科杂志

OBJECTIVE@#To explore the effect of chitosan (CS) hydrogel loaded with tendon-derived stem cells (TDSCs; hereinafter referred to as TDSCs/CS hydrogel) on tendon-to-bone healing after rotator cuff repair in rabbits.@*METHODS@#TDSCs were isolated from the rotator cuff tissue of 3 adult New Zealand white rabbits by Henderson step-by-step enzymatic digestion method and identified by multidirectional differentiation and flow cytometry. The 3rd generation TDSCs were encapsulated in CS to construct TDSCs/CS hydrogel. The cell counting kit 8 (CCK-8) assay was used to detect the proliferation of TDSCs in the hydrogel after 1-5 days of culture in vitro, and cell compatibility of TDSCs/CS hydrogel was evaluated by using TDSCs alone as control. Another 36 adult New Zealand white rabbits were randomly divided into 3 groups ( n=12): rotator cuff repair group (control group), rotator cuff repair+CS hydrogel injection group (CS group), and rotator cuff repair+TDSCs/CS hydrogel injection group (TDSCs/CS group). After establishing the rotator cuff repair models, the corresponding hydrogel was injected into the tendon-to-bone interface in the CS group and TDSCs/CS group, and no other treatment was performed in the control group. The general condition of the animals was observed after operation. At 4 and 8 weeks, real-time quantitative PCR (qPCR) was used to detect the relative expressions of tendon forming related genes (tenomodulin, scleraxis), chondrogenesis related genes (aggrecan, sex determining region Y-related high mobility group-box gene 9), and osteogenesis related genes (alkaline phosphatase, Runt-related transcription factor 2) at the tendon-to-bone interface. At 8 weeks, HE and Masson staining were used to observe the histological changes, and the biomechanical test was used to evaluate the ultimate load and the failure site of the repaired rotator cuff to evaluate the tendon-to-bone healing and biomechanical properties.@*RESULTS@#CCK-8 assay showed that the CS hydrogel could promote the proliferation of TDSCs ( P<0.05). qPCR results showed that the expressions of tendon-to-bone interface related genes were significantly higher in the TDSCs/CS group than in the CS group and control group at 4 and 8 weeks after operation ( P<0.05). Moreover, the expressions of tendon-to-bone interface related genes at 8 weeks after operation were significantly higher than those at 4 weeks after operation in the TDSCs/CS group ( P<0.05). Histological staining showed the clear cartilage tissue and dense and orderly collagen formation at the tendon-to-bone interface in the TDSCs/CS group. The results of semi-quantitative analysis showed that compared with the control group, the number of cells, the proportion of collagen fiber orientation, and the histological score in the TDSCs/CS group increased, the vascularity decreased, showing significant differences ( P<0.05); compared with the CS group, the proportion of collagen fiber orientation and the histological score in the TDSCs/CS group significantly increased ( P<0.05), while there was no significant difference in the number of cells and vascularity ( P>0.05). All samples in biomechanical testing failed at the repair site during the testing process. The ultimate load of the TDSCs/CS group was significantly higher than that of the control group ( P<0.05), but there was no significant difference compared to the CS group ( P>0.05).@*CONCLUSION@#TDSCs/CS hydrogel can induce cartilage regeneration to promote rotator cuff tendon-to-bone healing.

Hydrogels in the Treatment of Degenerative Tendinopathy / Hidrogeles en el Tratamiento de la Tendinopatía Degenerativa

Abstract: Degenerative tendinopathy is a significant health problem, and its incidence increases yearly. This condition causes functional deficits in young and adult patients and sedentary or active individuals, resulting in health, social, and economic consequences. Due to limited blood supply, drug administration is complex for tendon diseases, such as degenerative tendinopathy. Biomaterials, such as hydrogels, have gained significant attention in designing drug delivery systems to treat musculoskeletal pathologies due to their attractive characteristics and the challenges posed by conventional drug delivery routes. This paper provides an overview of tendon pathology and discusses the use of hydrogels as drug carriers and release agents in emerging treatments.

Resumen: La tendinopatía degenerativa es un importante problema de salud, y su incidencia aumenta cada año en todo el mundo. Esta condición genera déficits funcionales en pacientes jóvenes o adultos, así como en personas sedentarias o activas, trayendo consigo repercusiones sanitarias, sociales y económicas. Debido al suministro de sangre limitado, la administración de medicamentos es compleja para las enfermedades de los tendones, como la tendinopatía degenerativa. El uso de biomateriales, como los hidrogeles, ha ganado una atención significativa en el diseño de sistemas de administración de fármacos para tratar patologías musculoesqueléticas debido a sus atractivas características y los desafíos que plantean las rutas convencionales de administración de fármacos. Este documento proporciona una descripción general de la patología del tendón y analiza el uso de hidrogeles como transportadores de fármacos y agentes de liberación en tratamientos emergentes.

Novel Studies in the Designs of Natural, Synthetic, and Compound Hydrogels with Biomedical Applications / Novedosos Estudios en el Diseño de Hidrogeles Naturales, Sintéticos y Compuestos con Aplicaciones Biomédicas

ABSTRACT Hydrogels are gaining widespread popularity in the biomedical field due to their extraordinary properties, such as biocompatibility, biodegradability, zero toxicity, easy processing, and similarity to physiological tissue. They have applications in controlled drug release, wound dressing, tissue engineering, and regenerative medicine. Among these applications, hydrogels as a controlled drug delivery system stands out, which releases active substances in precise amounts and at specific times. To explore the latest advances in the design of hydrogels, a literature review of articles published in indexed scientific journals, in Scopus and Science Direct, was carried out. This review aimed to discover and describe the most innovative hydrogel research with applications in the biomedical field; hydrogels synthesized with polymers of different origins were selected, such as; i. Natural (dextran, agarose, chitosan, etc.); ii. Synthetic (polyacrylamide, polyethylene glycol, polyvinyl alcohol, etc.); iii. Composites (interpenetrants, hybrid crosslinkers, nanocomposites, etc.). Comparative analysis revealed that hydrogels with composite materials show the most promise. These composite hydrogels combine the advantages of different polymers or incorporate additional components, offering enhanced properties and functionalities. In summary, hydrogels are versatile biomaterials with immense potential in biomedicine. Their unique properties make them suitable for diverse applications. However, innovative designs and formulations must continue to be explored to further advance the capabilities of hydrogels and expand their biomedical applications.

RESUMEN Los hidrogeles están ganando una extensa popularidad en el campo biomédico gracias a que presentan propiedades extraordinarias como biocompatibilidad, biodegradabilidad, nula toxicidad, fácil procesamiento, y similitud con el tejido fisiológico. tienen aplicaciones en la liberación controlada de fármacos, el vendaje de heridas, la ingeniería de tejidos y la medicina regenerativa. Entre estas aplicaciones, destaca el uso de hidrogeles como sistema de administración controlada de fármacos, que liberan sustancias activas en cantidades precisas y en momentos concretos. Para explorar los últimos avances en el diseño de hidrogeles, se realizó una revisión bibliográfica de artículos publicados en revistas científicas indexadas, en Scopus y Science Direct. El objetivo de esta revisión fue descubrir y describir las investigaciones de hidrogeles más innovadoras con aplicaciones en el campo biomédico, se seleccionaron hidrogeles sintetizados con polímeros de diferente índole como; i. Naturales (dextrano, agarosa, quitosano, etc.); ii. Sintéticos (poliacrilamida, polietilenglicol, alcohol polivinílico, etc); iii. Compuestos (interpenetrantes, reticulantes híbridos, nanocompuestos, etc.). El análisis comparativo reveló que los hidrogeles que utilizan materiales compuestos son los más prometedores. Estos hidrogeles compuestos combinan las ventajas de distintos polímeros o incorporan componentes adicionales, ofreciendo propiedades y funcionalidades mejoradas. En resumen, los hidrogeles son biomateriales versátiles con un inmenso potencial en biomedicina. Sus propiedades únicas los hacen adecuados para diversas aplicaciones, sin embargo, se debe seguir explorando diseños y formulaciones innovadores para seguir avanzando en las capacidades de los hidrogeles y ampliar sus aplicaciones biomédicas.

Progress in research on hydrogel and medium permeability / 中国生物制品学杂志

@#As a new research field,gel has been paid more attention and widely used for studies on tissue engineering,drug delivery and biosensor. Hydrogel is the carrier of cells,while the cell survival and death are keys to the construction of tissues and organs. However,the cell viability and biological behavior are limited by the exchange of hydrogel and nutrients in medium. This review summarizes the types of hydrogel,exchange mode of hydrogel and nutrients in medium and the relevant influencing factors,which will provide a reference for the development and research of tissue bioengineering.

Research progress on the application of hydrogel spacer in brachytherapy for gynecological tumors / 中华放射肿瘤学杂志

Radiotherapy is an important treatment of gynecological tumors. Although novel techniques or measures in recemy years have improved the tumor control rate and reduced radiation toxicity, radiation toxicity remains a major problem due to the location of some key organs adjacent to the tumor. A new material-hydrogel, as an organ spacer, provides a new method to reduce the radiotherapy toxicity. In this article, the application of hydrogel as an organ spacer in brachytherapy for gynecological tumors was reviewed from the aspects of hydrogel characteristics, suitable population, mode of injection, interval distance and dose effect, clinical benefits and cost effectiveness, etc.

Research progress in the spacing and protection of hydrogels in radiotherapy for tumors / 中华放射医学与防护杂志

Radiotherapy is a primary method for treating tumors. However, since surrounding healthy tissues may also receive a certain dose of irradiation during the radiotherapy, they may suffer from radiation-induced damage, which is even serious for certain patients. Injectable hydrogels are expected to achieve the spacing between target areas and their surrounding tissues during radiotherapy, thus increasing the dose to the target areas while reducing the risk of radiation-induced damage to surrounding healthy tissues and organs. Accordingly, the quality of life of the patients can be improved. Therefore, applying injectable hydrogels serves as a potential strategy for reducing the adverse reactions associated with radiotherapy. This paper reviews the latest research progress in the spacing and protection of hydrogels in radiotherapy for different tumors.

Research progress in microenvironmentally responsive hydrogel materials for chronic refractory wounds / 国际生物医学工程杂志

Chronic refractory wounds have been a challenge for clinical treatment because of their diverse causative factors and complex pathological processes, long healing times, and high treatment costs. The microenvironment of the wound surface includes the external microenvironment of the periwound surface, the internal microenvironment of the wound surface, and subsurface physiological structures. Research on clinical treatment strategies based on the microenvironment of chronic refractory wounds continues to innovate and make progress. Hydrogels have the advantages of high-water content, adjustable performance, good biocompatibility, and similarity to extracellular matrix. The ability of hydrogels to load drugs and their modification to confer excellent tissue adhesion, antibacterial, antioxidant, and modulation of inflammatory factor expression can be used to achieve a multi-factor response and modulation of the physical, chemical, and biological aspects of the trauma microenvironment. Therefore, hydrogels have outstanding advantages and clinical application prospects in the repair of chronic, difficult-to-heal wounds. In this review paper, the characteristics and etiology of chronic refractory wounds were introduced, and the classification of microenvironment-responsive hydrogels for chronic refractory wounds and their application in the repair of refractory wounds were reviewed. Besides, the shortcomings of current hydrogels were discussed, and an outlook was proposed.

Research progress of the application of peptide hydrogel in the revascularization of pulp regeneration / 国际生物医学工程杂志

In recent years, problems such as the devitalization of dental pulp and the increased brittleness and fragility of teeth after root canal treatment have attracted more and more attention. Therefore, pulp regeneration has become the focus of research in endodontics and periapical disease, in which vascularization is of paramount importance. It is found that peptide hydrogel scaffolds have been widely applied because of their properties of impacting cell behavior, promoting angiogenesis, and being adaptable. In this review paper, the research progress of the application of peptide hydrogel in the vascularization of pulp regeneration and the properties of various peptide hydrogels were summarized to provide a reference for the further application of peptide hydrogel in pulp regeneration.

Preparation and performance evaluation on chitosan/gelatin hydrogel hemostatic material containing Panax notoginseng / 国际生物医学工程杂志

Objective:To prepare chitosan/gelatin hydrogel composite hemostatic materials loaded with Panax notoginseng (PN/CMC/GMs) and evaluate their performance. Methods:PN/CMC/GMs hydrogel composite hemostatic material were prepared by the freeze-drying method, and their morphology was observed by scanning electron microscopy. Their rheological properties were observed by a rheometer. Their water absorption rate was tested by dissolution. Their biocompatibility was detected by a cytotoxicity assay. Their rapid hemostatic effect was tested using a SD rat liver hemorrhage model.Results:PN/CMC/GMs composite hemostatic materials were prepared in a lattice-like structure with certain porosity. With the increase in Panax notoginseng powder content, the modulus of PN/CMC/GMs increased accordingly, and the mechanical strength increased. PN/CMC/GMs have better water absorption and expansion functions, which can form compression hemostasis and concentrated blood to achieve rapid hemostasis, and have good biocompatibility. Hemostasis experiments showed that the hemostatic time and hemostatic effect of PN, CMC/GMs hemostatic materials on liver injury in rats were better than those of the blank control group. Conclusions:PN/CMC/GMs have good hemostatic effect and biocompatibility and have the potential for further research and clinical application.

Cell-loaded hydrogel microspheres based on droplet microfluidics: a review / 生物工程学报

Droplet microfluidics technology offers refined control over the flows of multiple fluids in micro/nano-scale, enabling fabrication of micro/nano-droplets with precisely adjustable structures and compositions in a high-throughput manner. With the combination of proper hydrogel materials and preparation methods, single or multiple cells can be efficiently encapsulated into hydrogels to produce cell-loaded hydrogel microspheres. The cell-loaded hydrogel microspheres can provide a three-dimensional, relatively independent and controllable microenvironment for cell proliferation and differentiation, which is of great value for three-dimensional cell culture, tissue engineering and regenerative medicine, stem cell research, single cell study and many other biological science fields. In this review, the preparation methods of cell-loaded hydrogel microspheres based on droplet microfluidics and its applications in biomedical field are summarized and future prospects are proposed.

Preparation of silk fibroin/hyaluronic acid composite hydrogel based on thiol-ene click chemistry / 浙江大学学报·医学版

OBJECTIVES@#To design and prepare silk fibroin/hyaluronic acid composite hydrogel.@*METHODS@#The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by 1H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope.@*RESULTS@#The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good.@*CONCLUSIONS@#The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.

Preparation and properties of hydrogels loaded with phage endolysin Lys84 / 生物工程学报

This study investigated the application of poly(N-isopropylacrylamide)-based interpenetrating network temperature-sensitive hydrogels (notation: IPNT) as the delivery vehicle for phage endolysin Lys84 and the potential of drug-loaded hydrogels as antimicrobial materials. Interpenetrating network temperature-sensitive hydrogels were prepared by free radical polymerization of sodium alginate and N-isopropylacrylamide. Drug-loaded hydrogels (IPNT-Lys84) were obtained by dry soaking method with the endolysin Lys84 of Staphylococcus aureus phage. The physical properties of the hydrogels with and without drug loading were characterized by infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. The swelling and deswelling of the hydrogels as well as the release of endolysin Lys84 were investigated. Moreover, the antibacterial properties of IPNT-Lys84 hydrogels at different temperatures and concentrations of the drug solution were studied. The results showed that IPNT-Lys84 hydrogel had uniform pores and a low critical solubility temperature (LCST) of 32 ℃. The equilibrium swelling of the hydrogel was 30 g/g, and the water loss rate was 88% upon deswelling. The release rate of endolysin reached more than 70% within 6 h at 37 ℃. The bactericidal rate of IPNT-Lys84 hydrogel was over 99.9%. The research results showed the feasibility of using IPNT to deliver the endolysin Lys84, and IPNT-Lys84 hydrogel might be an effective antimicrobial material against multi-drug resistant Staphylococcus aureus.

A case report of Scleral Buckle implant mimicking an orbital tumor

Objective@#We report a case of a scleral buckle mimicking an orbital tumor 28 years after a retinal detachment repair.@*Methods@#This is a case report.@*Results@#A 75-year-old male consulted for progressive, painless blurred vision of the right eye. He had a history of scleral buckling surgery for retinal detachment on the right eye in 1990 that restored his vision. Examination showed right eye ophthalmoplegia and inferior displacement of the globe. Imaging revealed a right supero-temporal orbital mass. Excision of the encapsulated mass was performed. Histopathology revealed an acellular, amorphous, granular and eosinophilic material with no evidence of malignancy. These were consistent with a foreign body. Postoperatively, there were improvements in ocular motility and hypoglobus.@*Conclusion@#In patients who present with limited ocular motility and have undergone scleral buckling, hydrogel scleral buckle overexpansion should be considered. Excision of such implants is warranted to resolve the signs and symptoms and confirm the etiology.

Application of hydrogel-loaded stem cell exosomes in the field of tissue regeneration / 生物工程学报

In recent years, mesenchymal stem cell (MSCs)-derived exosomes have attracted much attention in the field of tissue regeneration. Mesenchymal stem cell-derived exosomes are signaling molecules for communication among cells. They are characterized by natural targeting and low immunogenicity, and are mostly absorbed by cells through the paracrine pathway of mesenchymal stem cells. Moreover, they participate in the regulation and promotion of cell or tissue regeneration. As a scaffold material in regenerative medicine, hydrogel has good biocompatibility and degradability. Combining the two compounds can not only improve the retention time of exosomes at the lesion site, but also improve the dose of exosomes reaching the lesion site by in situ injection, and the therapeutic effect in the lesion area is significant and continuous. This paper summarizes the research results of the interaction of exocrine and hydrogel composite materials to promote tissue repair and regeneration, in order to facilitate research in the field of tissue regeneration in the future.

Improvement effects of Shangke xiaoyan hydrogel plaster on osteoarthritis model rats / 中国药房

OBJECTIVE To study the improvement effects of Shangke xiaoyan hydrogel plaster on osteoarthritis （OA） model rats. METHODS Rats were randomly divided into blank group， model group， voltaren group （200 mg/rat）， Shangke xiaoyan ointment group （500 mg/rat， containing Shangke xiaoyan fluid extract 50 mg） and Shangke xiaoyan hydrogel plaster group （200 mg/rat， containing Shangke xiaoyan fluid extract 50 mg）， with 8 rats in each group. Except for blank group， OA model was established in the other groups by injecting papain and L-cysteine into the right knee joint cavity of the rats； they applied the corresponding drugs， and changed the dressing once a day， for 14 consecutive days. The degree of knee joint swelling in rats was detected， and the magnetic resonance imaging characteristics of the knee joint in rats were observed； the levels of interleukin 1β （IL-1β）， IL-6， IL-18 and tumor necrosis factor （TNF- α） in rat serum were detected； the pathological and morphological characteristics of knee joint tissue were observed， and the histopathological and cartilage Mankin scores were performed； the protein expressions of IL-1β， IL-6 and TNF-α in knee joint tissue were all detected. RESULTS Compared with blank group， severe joint swelling， obvious joint effusion and patchy wear of the anterior horn of the lateral meniscus were observed in model group； the serum levels of IL-1β， IL-6， IL-18 and TNF- α and histopathological score and Mankin score were significantly increased （P＜0.05）； protein expressions of IL-1β， IL-6 and TNF-α in knee joint tissue were increased. Compared with model group， the knee swelling degree of the rats in Shangke xiaoyan hydrogel plaster group was reduced， a small amount 　　 of joint cavity effusion could be seen， and the shape of the meniscus was completely normal； the histopathological score E-mail：frankyan@cpu.edu.cn and Mankin score were significantly reduced （P＜0.05）levels of inflammatory factors in serum were reduced （P＜0.05） and those of knee tissue were decreased. CONCLUSIONS Shangke xiaoyan hydrogel plaster can improve OA of rats， the mechanism of which may be associated with reducing the levels of inflammatory factors in joint and serum.

Predatory bacterial hydrogels for topical treatment of infected wounds

Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 μm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.

Bilayer hydrogel dressing with lysozyme-enhanced photothermal therapy for biofilm eradication and accelerated chronic wound repair

Biofilms are closely associated with the tough healing and dysfunctional inflammation of chronic wounds. Photothermal therapy (PTT) emerged as a suitable alternative which could destroy the structure of biofilms with local physical heat. However, the efficacy of PTT is limited because the excessive hyperthermia could damage surrounding tissues. Besides, the difficult reserve and delivery of photothermal agents makes PTT hard to eradicate biofilms as expectation. Herein, we present a GelMA-EGF/Gelatin-MPDA-LZM bilayer hydrogel dressing to perform lysozyme-enhanced PTT for biofilms eradication and a further acceleration to the repair of chronic wounds. Gelatin was used as inner layer hydrogel to reserve lysozyme (LZM) loaded mesoporous polydopamine (MPDA) (MPDA-LZM) nanoparticles, which could rapidly liquefy while temperature rising so as to achieve a bulk release of nanoparticles. MPDA-LZM nanoparticles serve as photothermal agents with antibacterial capability, could deeply penetrate and destroy biofilms. In addition, the outer layer hydrogel consisted of gelatin methacryloyl (GelMA) and epidermal growth factor (EGF) promoted wound healing and tissue regeneration. It displayed remarkable efficacy on alleviating infection and accelerating wound healing in vivo. Overall, the innovative therapeutic strategy we came up with has significant effect on biofilms eradication and shows promising application in promoting the repair of clinical chronic wounds.

Applicatoin of chitosan-based hydrogel in oral tissue engineering / 中南大学学报(医学版)

Pulpitis, periodontitis, jaw bone defect, and temporomandibular joint damage are common oral and maxillofacial diseases in clinic, but traditional treatments are unable to restore the structure and function of the injured tissues. Due to their good biocompatibility, biodegradability, antioxidant effect, anti-inflammatory activity, and broad-spectrum antimicrobial property, chitosan-based hydrogels have shown broad applicable prospects in the field of oral tissue engineering. Quaternization, carboxymethylation, and sulfonation are common chemical modification strategies to improve the physicochemical properties and biological functions of chitosan-based hydrogels, while the construction of hydrogel composite systems via carrying porous microspheres or nanoparticles can achieve local sequential delivery of diverse drugs or bioactive factors, laying a solid foundation for the well-organized regeneration of defective tissues. Chemical cross-linking is commonly employed to fabricate irreversible permanent chitosan gels, and physical cross-linking enables the formation of reversible gel networks. Representing suitable scaffold biomaterials, several chitosan-based hydrogels transplanted with stem cells, growth factors or exosomes have been used in an attempt to regenerate oral soft and hard tissues. Currently, remarkable advances have been made in promoting the regeneration of pulp-dentin complex, cementum-periodontium-alveolar bone complex, jaw bone, and cartilage. However, the clinical translation of chitosan-based hydrogels still encounters multiple challenges. In future, more in vivo clinical exploration under the conditions of oral complex microenvironments should be performed, and the combined application of chitosan-based hydrogels and a variety of bioactive factors, biomaterials, and state-of-the-art biotechnologies can be pursued in order to realize multifaceted complete regeneration of oral tissue.

Hydrogel loaded with exosomes from Wharton 's Jelly-derived mesenchymal stem cells enhances wound healing in mice / 浙江大学学报·医学版

OBJECTIVES@#To explore the effect of hydrogel loaded with exosomes from Wharton's Jelly-derived mesenchymal stem cell (WJMSC) on wound healing.@*METHODS@#Exosomes were extracted from WJMSC, and the morphology and size of WJMSC-derived exosomes (WEX) were analyzed by transmission electron microscopy and nanoparticle size analyzer, respectively. The surface markers CD9, CD81, and Calnexin of WEX were detected by Western blotting. Exosome-loaded alginate hydrogel (WEX-gel) was prepared; its morphology was studied by scanning electron microscope, and its rheological behavior was examined by a rheometer. The in vitro drug release performance of WEX-gel was investigated by BCA method. RAW264.7 cells were treated with alginate hydrogel, WEX and WEX-gel, respectively; and the expression of CD86 and CD206 in macrophages was detected by flow cytometry. A full-thickness skin wound model was established in mice; the model mice were randomly divided into blank control group, WEX control group and WEX-gel group, and PBS, WEX and WEX-gel were applied to the wound area of mice, respectively. On day 3, the skin tissue of mice was excised, and the antibacterial effect of WEX hydrogel was evaluated by plate counting. On day 15, the mice were euthanized and the percentage of residual wounds was calculated. The histological changes of the skin wound were observed after hematoxylin and eosin (HE) and Masson stainings. The expression of CD86, CD206, CD31 and vascular endothelial growth factor (VEGF) in the skin wound tissue was detected by immunohistochemistry.@*RESULTS@#Exosomes were successfully extracted from WJMSC. WEX-gel presented a regular three-dimensional network structure, good rheology and controlled drug release performance. WEX-gel promoted the polarization of RAW264.7 cells from the M1 phenotype to M2 phenotype in vitro. The residual wound percentage in blank control group, WEX control group and WEX-gel group were (27.5±3.4)%, (15.3±1.2)% and (7.6±1.1)%, respectively (P<0.05). The antibacterial property of WEX-gel is better than that of WEX (P<0.05). The dermis thickness, the number of new hair follicles, and the rate of collagen deposition in the WEX-gel group were significantly higher than those in the other two groups (all P<0.05). The expression of CD206, CD31 and VEGF in skin wound tissue was higher and the expression of CD86 was lower in WEX-gel group than those in other two groups (all P<0.05).@*CONCLUSIONS@#WEX-gel can significantly promote wound healing in mice by regulating the polarization of macrophages.