In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone gra...In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone grafts.To treat this life-threatening issue,improved biofunctional grafts capable of properly healing critical-sized bone defects are required.In this study,we effectively created anti-fracture hydrogel systems using spongy-like metal-organic(magnesium-phosphate)coordinated chitosan-modified injectable hydrogels(CPMg)loaded with a bioinspired neobavaisoflavone(NBF)component.The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphatebuffered saline.They also demonstrated prolonged and stable release profiles of Mg^(2+)and NBF.Importantly,CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells.To better understand the underlying mechanism of Mg^(2+)and NBF component,as well as their synergistic effect on osteogenesis,we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways.Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins(Runx2,OCN,OPN,BMPS and ALP).In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects.Based on these findings,we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.展开更多
Postoperative recurrence and metastasis are still the main challenges of cancer therapy.Tumor vaccines that induce potent and long-lasting immune activation have great potential for postoperative cancer therapy.Howeve...Postoperative recurrence and metastasis are still the main challenges of cancer therapy.Tumor vaccines that induce potent and long-lasting immune activation have great potential for postoperative cancer therapy.However,the clinical effects of therapeutic tumor vaccines are unsatisfactory due to immune escape caused by the lack of immunogenicity after surgery and the local fibrosis barrier of the tumor which limits effector T cell infiltration.To overcome these challenges,we developed an injectable hydrogelbased tumor vaccine,RATG,which contains whole tumor cell lysates(TCL),Toll-like receptor(TLR)7/8 agonist imiquimod(R837)and an antifibrotic drug ARV-825.TCL and R837 were loaded onto the hydrogel to achieve a powerful reservoir of antigens and adjuvants that induced potent and lasting immune activation.More importantly,ARV-825 could be slowly and sustainably released in the tumor resection cavity to downregulateα-smooth muscle actin(α-SMA)and collagen levels,disintegrate fibrosis barriers and promote T cell infiltration after immune activation to reduce immune escape.In addition,ARV-825 also directly acted on the remaining tumor cells to degrade bromodomain-containing protein 4(BRD4)which is a critical epigenetic reader overexpressed in tumor cells,inhibiting tumor cell migration and invasion.Therefore,our injectable hydrogel created a powerful immune niche in postoperative tumor resection cavity,significantly enhancing the efficacy of tumor vaccines.Our strategy potently activates the immune system and disintegrates the fibrotic barrier of residual tumors with immune microenvironment remodeling in situ,showing anti-recurrence and anti-metastatic effects,and provides a new paradigm for postoperative treatment of tumors.展开更多
Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac re...Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac repair efficiency post-MI, culminating in adverse ventricular remodeling and potential heart failure. To address the diverse pathological stages of MI, an injectable composite hydrogel containing versatile nanoparticles was developed. In this study, mesoporous silicon nanoparticles (MSNs) served as carriers for encapsulating microRNA-29b (miR-29b) mimics with antifibrotic activity, subsequently coated with a complex of natural antioxidant tannic acid and zinc ions (TA/Zn). These nanoparticles were then embedded into a biocompatible alginate hydrogel to enhance retention within the infarcted myocardium. Upon injection into the infarcted region of MI mice, the composite hydrogel gradually released the nanoparticles as it degraded. Initially, the TA/Zn complex on the outer layer scavenged reactive oxygen species, thereby inhibiting cell apoptosis. The subsequent dissociation of the TA/Zn complex led to the release of the encapsulated miR-29b mimics that could inhibit the activation of cardiac fibroblasts and collagen production, thereby alleviating fibrosis progression. Overall, this composite hydrogel demonstrated the potential to reduce infarct size and improve cardiac function, suggesting its promise as a synergistic therapeutic approach for repairing infarcted myocardium.展开更多
Myocardial infarction(MI)continues to be a leading cause of morbidity and mortality in cardiovascular diseases worldwide,severely compromising cardiac structure and function.While conventional treatments-including pha...Myocardial infarction(MI)continues to be a leading cause of morbidity and mortality in cardiovascular diseases worldwide,severely compromising cardiac structure and function.While conventional treatments-including pharmacological interventions,coronary artery bypass grafting(CABG),and percutaneous coronary intervention(PCI)-can effectively restore coronary blood flow,their ability to regenerate cardiomyocytes and substantially improve cardiac function remains limited.In this context,injectable hydrogels have emerged as a groundbreaking therapeutic approach,presenting remarkable potential for MI treatment owing to their exceptional biocompatibility,tunable mechanical properties,and versatile functionality.These hydrogels can form stable three-dimensional networks within infarcted myocardium,not only providing mechanical support to mitigate ventricular wall stress but also serving as delivery platforms for bioactive components such as growth factors,therapeutic drugs,and stem cells.Through multiple mechanisms-including attenuation of oxidative stress and calcium overload to protect cardiomyocytes,stimulation of angiogenesis to enhance tissue perfusion,and regulation of inflammatory responses to reduce fibrotic scarring-injectable hydrogels significantly promote myocardial repair and regeneration.Preclinical studies have consistently validated the therapeutic efficacy of various injectable hydrogel formulations in improving cardiac outcomes post-MI,highlighting their transformative potential in cardiovascular medicine.展开更多
Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)are well-established therapeutics for gastrointestinal neoplasias,but complications after EMR/ESD,including bleeding and perforation,result in ...Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)are well-established therapeutics for gastrointestinal neoplasias,but complications after EMR/ESD,including bleeding and perforation,result in additional treatment morbidity and even threaten the lives of patients.Thus,designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge.Herein,a series of injectable pH-responsive selfhealing adhesive hydrogels based on acryloyl-6-aminocaproic acid(AA)and AA-g-N-hydroxysuccinimide(AA-NHS)were developed,and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model.The hydrogels showed a suitable gelation time,an autonomous and efficient self-healing capacity,hemostatic properties,and good biocompatibility.With the introduction of AA-NHS as a micro-cross-linker,the hydrogels exhibited enhanced adhesive strength.A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding.A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition,α-SMA expression,and blood vessel formation.These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.展开更多
Baicalin,extracted from traditional Chinese medicine Scutellaria baicalensis Georg,possesses multiple pharmacological activities and has great potential for chronic skin wound repair.However,the poor solubility and la...Baicalin,extracted from traditional Chinese medicine Scutellaria baicalensis Georg,possesses multiple pharmacological activities and has great potential for chronic skin wound repair.However,the poor solubility and lack of suitable vehicles greatly limit its further application.Herein,we proposed a convenient and robust strategy,employing PBS solution as solvent,to enhance the solubility of baicalin.Furthermore,we constructed injectable baicalin/F127 hydrogels to study their application in skin wound treatment.The composition and temperature sensitivity of baicalin/Pluronic®F-127 hydrogels were confirmed by FTIR and rheological testing,respectively.In vitro release measurement indicated that the first order model was best fitted with the release profile of baicalin from hydrogel matrix.Besides,MTT assay,AO/EO staining assay as well as hemolytic activity test revealed the excellent cytocompatibility of baicalin/F127 hydrogels.Antioxidant activity assay demonstrated the cytoprotective activity of baicalin/F127 hydrogels against reactive oxygen species(ROS).Furthermore,the in vivo experiments exhibited the ability of baicalin/F127 hydrogel to accelerate wound healing.In conclusion,this novel injectable baicalin/F127 hydrogel should have bright application for chronic wound treatment.展开更多
Hydrogels with multifunctionalities,including sufficient bonding strength,injectability and self-healing capacity,responsive-adhesive ability,fault-tolerant and repeated tissue adhesion,are urgently demanded for invas...Hydrogels with multifunctionalities,including sufficient bonding strength,injectability and self-healing capacity,responsive-adhesive ability,fault-tolerant and repeated tissue adhesion,are urgently demanded for invasive wound closure and wound healing.Motivated by the adhesive mechanism of mussel and brown algae,bioinspired dynamic bonds cross-linked multifunctional hydrogel adhesive is designed based on sodium alginate(SA),gelatin(GT)and protocatechualdehyde,with ferric ions added,for sutureless post-wound-closure.The dynamic hydrogel cross-linked through Schiff base bond,catechol-Fe coordinate bond and the strong interaction between GT with temperature-dependent phase transition and SA,endows the resulting hydrogel with sufficient mechanical and adhesive strength for efficient wound closure,injectability and self-healing capacity,and repeated closure of reopened wounds.Moreover,the temperature-dependent adhesive properties endowed mispositioning hydrogel to be removed/repositioned,which is conducive for the fault-tolerant adhesion of the hydrogel adhesives during surgery.Besides,the hydrogels present good biocompatibility,near-infrared-assisted photothermal antibacterial activity,antioxidation and repeated thermo-responsive reversible adhesion and good hemostatic effect.The in vivo incision closure evaluation demonstrated their capability to promote the post-wound-closure and wound healing of the incisions,indicating that the developed reversible adhesive hydrogel dressing could serve as versatile tissue sealant.展开更多
The auto-gelling and drug release properties of the thermosensitive chitosan-β-glycerophosphate formulation were investigated. According to rheological study, gelation lag time of chitosan/β-glycerophosphate （GP） ...The auto-gelling and drug release properties of the thermosensitive chitosan-β-glycerophosphate formulation were investigated. According to rheological study, gelation lag time of chitosan/β-glycerophosphate （GP） solutions varied from 2 to 60min with different deacetylation degree of chitosan, pH, gelation temperature, and the particles in the sol. The gelation properties were also found to influence the release profilles of a hydrophilic drug, 5-fluorouracil （5-FU）. Morphological examination by scanning electron microphotography demonstrated that large ＂pores＂ occurred during the gel-forming process, which created hydrophilic environment and led to the rapid initial release of the drug （85% in f＇LrSt 8h）. Poly-3-hydroxybutyrate （PHB）, a biodegradable material, was applied here as scaffold to capture 5-FU into microparticles with high encapsulation efficiency by solvent-nonsolvent method. Combination of these microparticles into the chitosan-β-GP formulation could drop the rapid initial release from 85% down to 29% in the optimized PHB content （75%, by mass）. The release could sustain for about 10 months. Tiffs study provided an understanding of the potential of injectable implant using thermosensitive chitosan-β-GP formulation containing PHB based particles for the water soluble drugs that need the property of long-term delivery.展开更多
The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose(MC–CHO)and carboxymethyl chitosan(CMC).The copper sulfide nanoparticles...The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose(MC–CHO)and carboxymethyl chitosan(CMC).The copper sulfide nanoparticles(CuS NPs)and pH-sensitive doxorubicin-loaded zeolitic imidazolate frameworks nanoparticles(DOX@ZIF-8 NPs)were prepared and could be well-dispersed into the hydrogel system.The presence of CuS NPs can achieve photothermal therapy(PTT)for tumors under the irradiation of the near-infrared(NIR)laser.Moreover,CuS NPs can generate photodynamic effects under NIR irradiation,converting oxygen into toxic reactive oxygen species(ROS)and presenting efficient photodynamic therapy(PDT).The DOX@ZIF-8 NPs can be decomposed under an intracellular acidic environment and realize the controlled release of DOX.The injectable self-healing hydrogel loading Cu S and DOX@ZIF-8 NPs can achieve synergistic photothermal-photodynamic-chemo therapy for tumors and will inspire the researchers to construct a platform from hydrogel combined with multifunctional nanomaterials to realize the effective multimodal therapy for tumor.展开更多
Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation...Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation of exogenous CMs becomes a promising option for MI treatment.However,the low retention and survival of transplanted cells still limit the clinical translation of cell therapy.Herein,an alginate/fibrin-based injectable hydrogel was prepared for the delivery of neonatal CMs and an angiogen-esis agent vascular endothelial growth factor(VEGF)locally to the infarcted area of the heart.This hydro-gel combined the specific advantages of alginate and fibrin with proper mechanical properties and cell affinity,showing good biocompatibility to support the retention and integration of the transplanted CMs to the host myocardium.Moreover,the delivered VEGF was favorable for the blood recovery to mitigate the ischemic microenvironment of the infarcted area and thus improved the survival of the transplanted CMs.Intramyocardial injection of this hydrogel to the infarcted area of the heart promoted angiogenesis,inhibited fibrosis,and improved cardiac function,exhibiting great potential for MI treatment.展开更多
Injectable hydrogels as an important class of biomaterials have gained much attention in tissue engineering.However,their crosslinking degree is difficult to be controlled after being injected into body.As we all know...Injectable hydrogels as an important class of biomaterials have gained much attention in tissue engineering.However,their crosslinking degree is difficult to be controlled after being injected into body.As we all know,the crosslinking degree strongly influences the physicochemical properties of hydrogels.Therefore,developing an injectable hydrogel with tunable crosslinking degree in vivo is important for tissue engineering.Herein,we present a dual crosslinking strategy to prepare injectable hydrogels with step-by-step tunable crosslinking degree using Schiff base reaction and photopolymerization.The developed hyaluronic acid/poly(y-glutamic acid)(HA/y-PGA)hydrogels exhibit step-by-step tunable swelling behavior,enzymatic degradation behavior and mechanical properties.Mechanical performance tests show that the storage moduli of HA/y-PGA hydrogels are all less than 2000 Pa and the compressive moduli are in kilopascal,which have a good match with soft tissue.In addition,NIH 3T3 cells encapsulated in HA/y-PGA hydrogel exhibit a high cell viability,indicating a good cytocompatibility of HA/y-PGA hydrogel.Therefore,the developed HA/y-PGA hydrogel as an injectable biomaterial has a good potential in soft tissue engineering.展开更多
The present studies were conducted to compose an injectable solution of colistin sulfate containing local anaesthesia, antioxidant and other additions. Results showed that the novel preparation was stable either to he...The present studies were conducted to compose an injectable solution of colistin sulfate containing local anaesthesia, antioxidant and other additions. Results showed that the novel preparation was stable either to heat or to light. The term of validity of the preparation was 2 years at room temperature.The preparation containing 25. 0 mg ml-1 colistin sulfate showed no local tissue irritation, but the concentration of 50. 0 mg ml-1 colistin sulfate showed obvious local tissue irritation. Result of acute toxicity test showed that the LD50 of intramuscular injection in mice was 38. 72 mg kg-1, and oral LD50 was 431. 39 mg kg-1. The evidence of neurotoxicity was observed in mice in the acute toxicity test. A dose of 10.0 mg kg-1 b. w. or 15:0 mg kg-1b. w. was administered intramuscularly to piglet once daily for 5 days. No changes were detected in the piglet body except for the slight epithelial tissue's granular degenerations in the kidney and liver at the dose of the 10.0 mg kg-1. While at the dose of 15. 0 mg kg-1, the obvious neurotoxicity was observed at 4-5 days. The epithelial tissues in the kidney and liver showed moderate granular degenerations, especially in the tubuli renales cells. Blood cell's morphosis indexes were normal. With relation to liver's function, the indexes went beyond the normal scope. But with relation to kidney's function, the indexes showed mostly normal.When the preparation was separately administered into muscle(i. m.) in piglets with the dose of 2. 5 and 5. 0 mg kg-1 b. w, whose Cmax were 3.73±0. 28 and 6. 40±0.18 Abstract:g ml-1; Tmax were 32±1. 5 and 34±1.8min; t1/2β were 256±14 min and 264±29 min, respectively. t1/2βt was 251±13 min for the injection given into aural vein( i. v.) with the dose of 2.5 mg kg1-1 b. w.. Samples of the experimentally determined plasma concentration of colistin sulfate generated two-exponential model with first-order absorption. The mean absolute bioavail-ability coefficient of 2.5 and 5. 0 mg kg-1 b. w. (i. m.) were 98. 30 and 88. 54%, respectively. The high bio-availability and the long maintaining time of the valid blood-drug concentration showed that the injectable solution was suitable for i. m. in pigs, whose recommended dose was 2.5 mg kg-1 b. w. , twice daily.展开更多
Aim： To report our experience with penile girth augmentation using liquid injectable silicone. Methods： Between August 2003 and July 2006, 324 men （mean age 35 years, range 19-65 years） received a series of liquid...Aim： To report our experience with penile girth augmentation using liquid injectable silicone. Methods： Between August 2003 and July 2006, 324 men （mean age 35 years, range 19-65 years） received a series of liquid silicone subcutaneous injections between the penile skin and the corpora cavernosa on the dorsal and lateral aspects of the penile shaft, under local anesthesia. Digital photographs taken pre- and post-procedure （n = 324）, and penile contour measurements （n = 30） yielded objective results. Subjective results were derived from patient and partner testimony of satisfaction. Follow-up averaged 20 months （range 1-36 months）. Results： Three hundred and twenty-four procedures were primary augmentations. Most men （61%） were married, 7% were accompanied by their partners, and 93% were circumcised. The mean measured penile circumference was 9.5 cm （7.5-11.5 cm） pretreatment and 12.1 cm （10.3-15.3 cm） post-treatment （mean increase of 27% in circumference and 0.84 cm in diameter）. Patient and partner satisfaction was already expressed after the first two treatments. Sexual activity could be resumed after 8 h. Complications （mild bruising） were easily resolved. Conclusion： Penile girth augmentation using liquid injectable silicone yields very satisfactory short-term results with no immediate or short-term complications.展开更多
Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self...Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self-healing nano hybrid hydrogel was on-demand prepared via a fast(within 30 s)and easy gelation approach by reversible Schiff base formed between-CH=O of oxidized sodium alginate(OSA)and-NH2 of glycol chitosan(GCS)mixed with calcium phosphate nanoparticles(CaP NPs).Its raw materials can be ready in large quantities by a simple synthesis process.The mechanical strength,degradation and swelling behavior of the hydrogel can be readily controlled by simply controlling the molar ratio of-CH=O and-NH2.This hydrogel exhibits pH responsiveness,good degradability and biocompatibility.The hydrogel used as the matrix for mesenchymal stem cells can significantly induce the proliferation,differentiation and osteoinduction in vitro.These results showed this novel hydrogel is an ideal candidate for applications in bone tissue regeneration and drug delivery.展开更多
A luminescent and injectable supramolecular hydrogel was successfully constructed through the non- covalent cross-linking of polymers mediated by tetraphenylethylene-bridged cyclodextrin oligomers, presenting the stro...A luminescent and injectable supramolecular hydrogel was successfully constructed through the non- covalent cross-linking of polymers mediated by tetraphenylethylene-bridged cyclodextrin oligomers, presenting the strong blue fluorescence, the reversible gelation behavior responsive to various external stimuli and the good mechanical property of shear thinning.展开更多
The increasing incidence of osteoarthritis(OA) seriously affects life quality,posing a huge socioeco nomic burden.Tissue engineering technology has become a hot topic in articular cartilage repair as one of the key tr...The increasing incidence of osteoarthritis(OA) seriously affects life quality,posing a huge socioeco nomic burden.Tissue engineering technology has become a hot topic in articular cartilage repair as one of the key treatment methods to alleviate OA.Hydrogel,one of the most commonly used scaffold materials,ca n provide a good extracellular matrix microenvironment fo r seed cells such as bone marrow mesenchymal stem cells(BMSCs),which can promote cartilage regeneration.However,the low homing rate of stem cells severely limits their role in promoting articular cartilage regeneration.Stro mal cell-derived factor-1α(SDF-1α) plays a crucial role in the activatio n,mobilization,homing,and migration of MSCs.He rein,a novel injectable chemotaxis hydrogel,composed of chitosan-based injectable hydrogel and embedding SDF-1α-loaded nanodroplets(PFP@NDs-PEG-SDF-1α) was designed and fabricated.The ultrasound was then used to augment the injectable chemotaxis hydrogel and promote the homing migration of BMSCs for OA cartilage repair.The effect of ultrasound augmenting injectable PFP@NDs-PEG-SDF-1α/hydrogel on the migration of BMSCs was verified in vitro and in vivo,which re markably promotes stem cell homing and the repair of cartilage in the OA model.Therefore,the treatment strategy of ultrasound augmenting injectable chemotaxis hydrogel has a bright potential for OA articular cartilage repair.展开更多
BACKGROUND Given the low survival rate in pancreatic cancer,new therapeutic techniques have been explored,especially for unresectable or borderline resectable disease.Endoscopic ultrasound(EUS)provides real-time imagi...BACKGROUND Given the low survival rate in pancreatic cancer,new therapeutic techniques have been explored,especially for unresectable or borderline resectable disease.Endoscopic ultrasound(EUS)provides real-time imaging and minimally invasive access for local and targeted injection of anti-tumor agents directly into the pancreatic tumor.Limited studies have been reported using this technique for the treatment of pancreatic ductal adenocarcinoma(PDAC).AIM To evaluate the progress made with EUS-guided injectable therapies in the treatment of PDAC.METHODS All original articles published in English until July 15,2021,were retrieved via a library-assisted literature search from Ovid Evidence-Based Medicine Reviews and Scopus databases.Reference lists were reviewed to identify additional relevant articles.Prospective clinical studies evaluating the use of EUS-guided injectable therapies in PDAC were included.Studies primarily directed at non-EUS injectable therapies and other malignancies were excluded.Retrieved manuscripts were reviewed descriptively with on critical appraisal of published studies based on their methods and outcome measures such as safety,feasibility,and effectiveness in terms of tumor response and survival.Heterogeneity in data outcomes and therapeutic techniques limited the ability to perform comparative statistical analysis.RESULTS A total of thirteen articles(503 patients)were found eligible for inclusion.The EUS-injectable therapies used were heterogeneous among the studies consisting of immunotherapy(n=5)in 59 patients,chemotherapy(n=1)in 36 patients,and viral and other biological therapies(n=7)in 408 patients.Eleven of the studies reviewed were single armed while two were double armed with one randomized trial and one non-randomized comparative study.Overall,the included studies demonstrated EUS-guided injectable therapies to be safe and feasible with different agents as monotherapy or in conjunction with other modalities.Promising results were also observed regarding their efficacy and survival parameters in patients with PDAC.CONCLUSION EUS-guided injectable therapies,including immunotherapy,chemotherapy,and viral or other biological therapies have shown minimal adverse events and potential efficacy in the treatment of PDAC.Comparative studies,including controlled trials,are required to confirm these results in order to offer novel EUS-based treatment options for patients with PDAC.展开更多
Implantable system maximizes drug concentration and continuously releases drugs near the tumor,which is an effective tool to solve the difficult retention of chemotherapy drugs in bladder cancer.In this work,a novel p...Implantable system maximizes drug concentration and continuously releases drugs near the tumor,which is an effective tool to solve the difficult retention of chemotherapy drugs in bladder cancer.In this work,a novel polysaccharide supramolecular injectable hydrogel(CCA hydrogels for short)is rapidly constructed by simply mixing cationic chitosan,anionic sulfobutyl etherβ-cyclodextrin(SBE-β-CD)and a trace amount of silver ions.The injected hydrogel reconstituted and regained its shape in less than 1 h,and it can still maintain the elasticity suitable for the human body.By packaging the drug directly,the gel achieves a high concentration of doxorubicin,an anticancer drug.Using MB49-luc cells as the model of bladder tumor for anti-tumor in vivo,the CCA-DOX gel has obvious inhibitory effect on bladder tumor,and its inhibitory effect is much greater than that of free DOX.Therefore,this self-healing injectable hydrogel has great potential for in situ treatment of bladder cancer.展开更多
Background: There is a large assortment of modalities for the surgical treatment/management of distal radius fractures (DRFs), where the most widely used is the fixed-angle volar plating (VLP) system, which, sometimes...Background: There is a large assortment of modalities for the surgical treatment/management of distal radius fractures (DRFs), where the most widely used is the fixed-angle volar plating (VLP) system, which, sometimes, is referred to as the “surgical modality of choice”. While outcomes with each modality are usually good to excellent, each has its share of shortcomings and complications. Thus, there is scope for improvements to existing modalities and/or introduction of new ones. Study Purpose: We introduce a novel modality, namely, the prototype of an intramedullary injectable bioresorbable polymer-bioresorbable balloon osteosynthesis (IPBO) system, and investigated its plausibility. Experimental Procedures: The biomechanical performance of a construct comprising a synthetic distal radius (fourth-generation Sawbones?) on which a simulated fracture was created (4-mm wide osteotomy positioned 25 mm from the most distal end of the radius) and fixated with a placement of the IPBO system (SIPBO Construct) was compared to that when the fixation was with an approved Ti-6Al-4V alloy VLP system (SVLP Construct), under a clinically-relevant compressive loading protocol. Performance involved determination of quantitative parameters of the construct (initial longitudinal stiffness (ICLS), final longitudinal stiffness (FCLS), and load-to-failure (Pf)) and observation and recording of features of the construct at the fracture point. We also determined the quantitative parameters for the intact synthetic distal radius (control). Results: For each of the quantitative parameters, the range of values for SIPBO Construct was within that for SVLP Construct, suggesting that the IPBO System is a plausible modality. Also, for SIPBO Construct, failure occurred within the polymer zone, whereas, for SVLP Construct, some failure features were fracture of the cortical wall and of the dorsal proximal fragments. Conclusion: The findings suggest that the IPBO system is plausible. As such, it merits further study;for example, determination of the influence of fracture gap fill ratio (defined as the proportion of the fracture gap that is filled by the expanding balloon as the polymer is injected into the balloon) on a large collection of quantitative biomechanical parameters.展开更多
BACKGROUND Collagen membrane and platelet-rich fibrin(PRF)have emerged as vital biomaterials in the field of periodontal regeneration.Minimally invasive techniques are being preferred by most periodontists,as it is pa...BACKGROUND Collagen membrane and platelet-rich fibrin(PRF)have emerged as vital biomaterials in the field of periodontal regeneration.Minimally invasive techniques are being preferred by most periodontists,as it is patient compliant with fewer post-surgical complications as compared to conventional surgical techniques.Thus,in this study we have evaluated the effect of injectable PRF(i-PRF)with collagen membrane compared with collagen membrane alone using vestibular incision subperiosteal tunnel access(VISTA)technique for gingival recession coverage.AIM To compare the efficacy of VISTA using collagen membrane with collagen membrane soaked in injectable PRF for gingival recession coverage.METHODS A split mouth randomized controlled clinical trial was designed;13 subjects having at least 2 teeth indicated for recession coverage were enrolled in this study.The sites were randomly assigned to control group(VISTA using collagen membrane alone)and the test group(VISTA using collagen membrane with i-PRF).The clinical parameters assessed were pocket depth,recession depth(RD),recession width(RW),relative attachment level,keratinised tissue width(KTW),keratinised tissue thickness(KTT),and percentage root coverage.RESULTS RD showed a statistically significant difference between the test group at 3 mo(0.5±0.513)and 6 mo(0.9±0.641)and the control group at 3 mo(0.95±0.51)and 6 mo(1.5±0.571),with P values of 0.008 and 0.04,respectively.RW also showed a statistically significant difference between the test group at 3 mo(1±1.026)and 6 mo(1.65±1.04)and the control group at 3 mo(1.85±0.875)and 6 mo(2.25±0.759),with P values of 0.008 and 0.001,respectively.Results for KTW showed statistically significant results between the test group at 1 mo(2.85±0.489),3 mo(3.5±0.513),and 6 mo(3.4±0.598)and the control group at 1 mo(2.45±0.605),3 mo(2.9±0.447),and 6 mo(2.75±0.444),with P values of 0.04,0.004,and 0.003,respectively.Results for KTT also showed statistically significant results between test group at 1 mo(2.69±0.233),3 mo(2.53±0.212),and 6 mo(2.46±0.252)and the control group at 1 mo(2.12±0.193),3 mo(2.02±0.18),and 6 mo(1.91±0.166),with P values of 0.001,0.001,and 0.001,respectively.The test group showed 91.6%,81.6%,and 67%root coverage at 1 mo,3 mo,and 6 mo,while the control group showed 82.3%,66.4%,and 53.95%of root coverage at 1 mo,3 mo,and 6 mo,respectively.CONCLUSION The use of minimally invasive VISTA technique along with collagen membrane and injectable form of platelet-rich fibrin can be successfully used as a treatment method for multiple or isolated gingival recessions of Miller’s class-I and class-II defects.展开更多
基金supported by Natural Science Foundation of China(No.82202664,82172432,U22A20371)Shenzhen Sustainable Development Project(No.KCXFZ20201221173411031)+4 种基金Shenzhen Science and Technology Program(JCYJ20220818102815033,National Science Foundation of Guangdong Province(No.2021A1515220053,2022A1515010034,2021B1515120061)Guangdong Basic and Applied Basic Research Foundation(No.2019A1515110983,2022A1515012663)Guangzhou Basic and Applied Basic Research Foundation(202102021160)the Fundamental Research Funds for the Central Universities(21624221)the Research Fund Program of Guangdong Provincial Key Laboratory of Speed Capability Research(2023B1212010009).
文摘In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone grafts.To treat this life-threatening issue,improved biofunctional grafts capable of properly healing critical-sized bone defects are required.In this study,we effectively created anti-fracture hydrogel systems using spongy-like metal-organic(magnesium-phosphate)coordinated chitosan-modified injectable hydrogels(CPMg)loaded with a bioinspired neobavaisoflavone(NBF)component.The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphatebuffered saline.They also demonstrated prolonged and stable release profiles of Mg^(2+)and NBF.Importantly,CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells.To better understand the underlying mechanism of Mg^(2+)and NBF component,as well as their synergistic effect on osteogenesis,we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways.Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins(Runx2,OCN,OPN,BMPS and ALP).In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects.Based on these findings,we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.
基金supported by the National Natural Science Foundation of China(No.82102202)Key Research and Development Program Social Development Project of Jiangsu Province(No.BE2023845)Natural Science Foundation of Jiangsu Province(No.BK20210424).
文摘Postoperative recurrence and metastasis are still the main challenges of cancer therapy.Tumor vaccines that induce potent and long-lasting immune activation have great potential for postoperative cancer therapy.However,the clinical effects of therapeutic tumor vaccines are unsatisfactory due to immune escape caused by the lack of immunogenicity after surgery and the local fibrosis barrier of the tumor which limits effector T cell infiltration.To overcome these challenges,we developed an injectable hydrogelbased tumor vaccine,RATG,which contains whole tumor cell lysates(TCL),Toll-like receptor(TLR)7/8 agonist imiquimod(R837)and an antifibrotic drug ARV-825.TCL and R837 were loaded onto the hydrogel to achieve a powerful reservoir of antigens and adjuvants that induced potent and lasting immune activation.More importantly,ARV-825 could be slowly and sustainably released in the tumor resection cavity to downregulateα-smooth muscle actin(α-SMA)and collagen levels,disintegrate fibrosis barriers and promote T cell infiltration after immune activation to reduce immune escape.In addition,ARV-825 also directly acted on the remaining tumor cells to degrade bromodomain-containing protein 4(BRD4)which is a critical epigenetic reader overexpressed in tumor cells,inhibiting tumor cell migration and invasion.Therefore,our injectable hydrogel created a powerful immune niche in postoperative tumor resection cavity,significantly enhancing the efficacy of tumor vaccines.Our strategy potently activates the immune system and disintegrates the fibrotic barrier of residual tumors with immune microenvironment remodeling in situ,showing anti-recurrence and anti-metastatic effects,and provides a new paradigm for postoperative treatment of tumors.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK20231314)the National Natural Science Foundation of China(No.92168203)+4 种基金the National Key R&D Program of China(No.2022YFA1104300)the Jiangsu Cardiovascular Medicine Innovation Center(No.CXZX202210)the Suzhou“Science and Education Revitalize Health”Youth Science and Technology Project(No.KJXW2021001)the Suzhou“Science and Education Revitalize Health”Youth Science and Technology Project(No.KJXW2021001)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac repair efficiency post-MI, culminating in adverse ventricular remodeling and potential heart failure. To address the diverse pathological stages of MI, an injectable composite hydrogel containing versatile nanoparticles was developed. In this study, mesoporous silicon nanoparticles (MSNs) served as carriers for encapsulating microRNA-29b (miR-29b) mimics with antifibrotic activity, subsequently coated with a complex of natural antioxidant tannic acid and zinc ions (TA/Zn). These nanoparticles were then embedded into a biocompatible alginate hydrogel to enhance retention within the infarcted myocardium. Upon injection into the infarcted region of MI mice, the composite hydrogel gradually released the nanoparticles as it degraded. Initially, the TA/Zn complex on the outer layer scavenged reactive oxygen species, thereby inhibiting cell apoptosis. The subsequent dissociation of the TA/Zn complex led to the release of the encapsulated miR-29b mimics that could inhibit the activation of cardiac fibroblasts and collagen production, thereby alleviating fibrosis progression. Overall, this composite hydrogel demonstrated the potential to reduce infarct size and improve cardiac function, suggesting its promise as a synergistic therapeutic approach for repairing infarcted myocardium.
基金supported by the funding listed as follows:National Natural Science Foundation of China(No.32301115)Sichuan Science and Technology Program(2025ZNSFSC0245)+3 种基金National Key Research and Development Program of China(2023YFC2412802)the Fundamental Research Funds for the Central Universities(2023SCUH0011,No.YJ2021115)Med-X Innovation Programme of Med-X Center of Materials,Sichuan University,China(Grant No.MCMGD202303)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences[CIFMS,(No.2021-I2M-5-013)].
文摘Myocardial infarction(MI)continues to be a leading cause of morbidity and mortality in cardiovascular diseases worldwide,severely compromising cardiac structure and function.While conventional treatments-including pharmacological interventions,coronary artery bypass grafting(CABG),and percutaneous coronary intervention(PCI)-can effectively restore coronary blood flow,their ability to regenerate cardiomyocytes and substantially improve cardiac function remains limited.In this context,injectable hydrogels have emerged as a groundbreaking therapeutic approach,presenting remarkable potential for MI treatment owing to their exceptional biocompatibility,tunable mechanical properties,and versatile functionality.These hydrogels can form stable three-dimensional networks within infarcted myocardium,not only providing mechanical support to mitigate ventricular wall stress but also serving as delivery platforms for bioactive components such as growth factors,therapeutic drugs,and stem cells.Through multiple mechanisms-including attenuation of oxidative stress and calcium overload to protect cardiomyocytes,stimulation of angiogenesis to enhance tissue perfusion,and regulation of inflammatory responses to reduce fibrotic scarring-injectable hydrogels significantly promote myocardial repair and regeneration.Preclinical studies have consistently validated the therapeutic efficacy of various injectable hydrogel formulations in improving cardiac outcomes post-MI,highlighting their transformative potential in cardiovascular medicine.
基金This work was jointly supported by the National Natural Science Foundation of China(grant Nos.:51973172,51673155,81201927,82002957 and 81672460)the National Key Research and Development Plan of China(No.2018YFC0115300)+5 种基金the State Key Laboratory for Mechanical Behavior of Materials,the World-Class Universities(Disciplines)the Characteristic Development Guidance Funds for the Central Universities,the Natural Science Foundation of Shaanxi Province(No.2020JC-03 and 2019TD-020)the Innovation Talent Promotion Plan of Shaanxi(No.2017KJXX-07)the Key Research and Development Program of Shaanxi Province(No.2019SF-012)the Opening Project of Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,College of Stomatology,Xi’an Jiaotong University(No.2019LHM-KFKT008)Fundamental Research Funds for the Central Universities of China(No.xjj2018090).
文摘Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)are well-established therapeutics for gastrointestinal neoplasias,but complications after EMR/ESD,including bleeding and perforation,result in additional treatment morbidity and even threaten the lives of patients.Thus,designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge.Herein,a series of injectable pH-responsive selfhealing adhesive hydrogels based on acryloyl-6-aminocaproic acid(AA)and AA-g-N-hydroxysuccinimide(AA-NHS)were developed,and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model.The hydrogels showed a suitable gelation time,an autonomous and efficient self-healing capacity,hemostatic properties,and good biocompatibility.With the introduction of AA-NHS as a micro-cross-linker,the hydrogels exhibited enhanced adhesive strength.A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding.A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition,α-SMA expression,and blood vessel formation.These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.
基金the National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2018ZX10301402)International Cooperation and Exchange of the National Natural Science Foundation of China(No.51820105004)+3 种基金Science and Technology Program of Guangzhou(No.201707010094)Guangdong Innovative and Entrepreneurial Research Team Program(Nos.2013S086 and 2016ZT06S029)Science and Technology Planning Project of Shenzhen(Nos.JCYJ20170307141438157 and JCYJ20180307163534533)Fundamental Research Funds for the Central Universities(No.191gpy209)。
文摘Baicalin,extracted from traditional Chinese medicine Scutellaria baicalensis Georg,possesses multiple pharmacological activities and has great potential for chronic skin wound repair.However,the poor solubility and lack of suitable vehicles greatly limit its further application.Herein,we proposed a convenient and robust strategy,employing PBS solution as solvent,to enhance the solubility of baicalin.Furthermore,we constructed injectable baicalin/F127 hydrogels to study their application in skin wound treatment.The composition and temperature sensitivity of baicalin/Pluronic®F-127 hydrogels were confirmed by FTIR and rheological testing,respectively.In vitro release measurement indicated that the first order model was best fitted with the release profile of baicalin from hydrogel matrix.Besides,MTT assay,AO/EO staining assay as well as hemolytic activity test revealed the excellent cytocompatibility of baicalin/F127 hydrogels.Antioxidant activity assay demonstrated the cytoprotective activity of baicalin/F127 hydrogels against reactive oxygen species(ROS).Furthermore,the in vivo experiments exhibited the ability of baicalin/F127 hydrogel to accelerate wound healing.In conclusion,this novel injectable baicalin/F127 hydrogel should have bright application for chronic wound treatment.
基金supported by the National Natural Science Foundation of China (No. 51973172)Natural Science Foundation of Shaanxi Province (Nos. 2020JC-03 and 2019TD-020)+2 种基金the State Key Laboratory for Mechanical Behavior of Materials,the World-Class Universities (Disciplines) and Characteristic Development Guidance Funds for the Central UniversitiesFundamental Research Funds for the Central Universitiesthe Opening Project of the Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,College of Stomatology,Xi’an Jiaotong University (No. 2019LHM-KFKT008).
文摘Hydrogels with multifunctionalities,including sufficient bonding strength,injectability and self-healing capacity,responsive-adhesive ability,fault-tolerant and repeated tissue adhesion,are urgently demanded for invasive wound closure and wound healing.Motivated by the adhesive mechanism of mussel and brown algae,bioinspired dynamic bonds cross-linked multifunctional hydrogel adhesive is designed based on sodium alginate(SA),gelatin(GT)and protocatechualdehyde,with ferric ions added,for sutureless post-wound-closure.The dynamic hydrogel cross-linked through Schiff base bond,catechol-Fe coordinate bond and the strong interaction between GT with temperature-dependent phase transition and SA,endows the resulting hydrogel with sufficient mechanical and adhesive strength for efficient wound closure,injectability and self-healing capacity,and repeated closure of reopened wounds.Moreover,the temperature-dependent adhesive properties endowed mispositioning hydrogel to be removed/repositioned,which is conducive for the fault-tolerant adhesion of the hydrogel adhesives during surgery.Besides,the hydrogels present good biocompatibility,near-infrared-assisted photothermal antibacterial activity,antioxidation and repeated thermo-responsive reversible adhesion and good hemostatic effect.The in vivo incision closure evaluation demonstrated their capability to promote the post-wound-closure and wound healing of the incisions,indicating that the developed reversible adhesive hydrogel dressing could serve as versatile tissue sealant.
基金Supported by the National Natural Science Foundation of China (No.20376038) and the Research Foundation of the Ministry ofEducation of China (No.2002003056).
文摘The auto-gelling and drug release properties of the thermosensitive chitosan-β-glycerophosphate formulation were investigated. According to rheological study, gelation lag time of chitosan/β-glycerophosphate （GP） solutions varied from 2 to 60min with different deacetylation degree of chitosan, pH, gelation temperature, and the particles in the sol. The gelation properties were also found to influence the release profilles of a hydrophilic drug, 5-fluorouracil （5-FU）. Morphological examination by scanning electron microphotography demonstrated that large ＂pores＂ occurred during the gel-forming process, which created hydrophilic environment and led to the rapid initial release of the drug （85% in f＇LrSt 8h）. Poly-3-hydroxybutyrate （PHB）, a biodegradable material, was applied here as scaffold to capture 5-FU into microparticles with high encapsulation efficiency by solvent-nonsolvent method. Combination of these microparticles into the chitosan-β-GP formulation could drop the rapid initial release from 85% down to 29% in the optimized PHB content （75%, by mass）. The release could sustain for about 10 months. Tiffs study provided an understanding of the potential of injectable implant using thermosensitive chitosan-β-GP formulation containing PHB based particles for the water soluble drugs that need the property of long-term delivery.
基金the National Natural Science Foundation of China(No.82172040)。
文摘The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose(MC–CHO)and carboxymethyl chitosan(CMC).The copper sulfide nanoparticles(CuS NPs)and pH-sensitive doxorubicin-loaded zeolitic imidazolate frameworks nanoparticles(DOX@ZIF-8 NPs)were prepared and could be well-dispersed into the hydrogel system.The presence of CuS NPs can achieve photothermal therapy(PTT)for tumors under the irradiation of the near-infrared(NIR)laser.Moreover,CuS NPs can generate photodynamic effects under NIR irradiation,converting oxygen into toxic reactive oxygen species(ROS)and presenting efficient photodynamic therapy(PDT).The DOX@ZIF-8 NPs can be decomposed under an intracellular acidic environment and realize the controlled release of DOX.The injectable self-healing hydrogel loading Cu S and DOX@ZIF-8 NPs can achieve synergistic photothermal-photodynamic-chemo therapy for tumors and will inspire the researchers to construct a platform from hydrogel combined with multifunctional nanomaterials to realize the effective multimodal therapy for tumor.
基金financially supported by the National Natural Science Foundation of China (Nos.92168203 and 22175125)the Extracurricular Scientific Research Project for Students of Suzhou Medical College of Soochow University (No.2021YXBKWKY070)+3 种基金the Scientific Research Innovation Project for Graduate Students of Jiangsu Province (No.KYCX22_3189)the Introduction Project of Clinical Medicine Expert Team for Suzhou (No.SZYJTD201704)the Natural Science Foundation of the Jiangsu Higher Education Insti-tutions of China (No.21KJA150008)the Priority Academic Pro-gram Development of Jiangsu Higher Education Institutions (PAPD).
文摘Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation of exogenous CMs becomes a promising option for MI treatment.However,the low retention and survival of transplanted cells still limit the clinical translation of cell therapy.Herein,an alginate/fibrin-based injectable hydrogel was prepared for the delivery of neonatal CMs and an angiogen-esis agent vascular endothelial growth factor(VEGF)locally to the infarcted area of the heart.This hydro-gel combined the specific advantages of alginate and fibrin with proper mechanical properties and cell affinity,showing good biocompatibility to support the retention and integration of the transplanted CMs to the host myocardium.Moreover,the delivered VEGF was favorable for the blood recovery to mitigate the ischemic microenvironment of the infarcted area and thus improved the survival of the transplanted CMs.Intramyocardial injection of this hydrogel to the infarcted area of the heart promoted angiogenesis,inhibited fibrosis,and improved cardiac function,exhibiting great potential for MI treatment.
基金the National Natural Science Foundation of China(No.31771049)Foundation of key R&D Project of Jiangsu Province(No.BE2018731)+1 种基金Research Foundation of State Key Laboratory of Materials-Oriented Chemical Engineering(Nos.ZK201806 and No.KLI 8-06)the Six Talent Peaks Project of Jiangsu Province(No.SWYY-046)。
文摘Injectable hydrogels as an important class of biomaterials have gained much attention in tissue engineering.However,their crosslinking degree is difficult to be controlled after being injected into body.As we all know,the crosslinking degree strongly influences the physicochemical properties of hydrogels.Therefore,developing an injectable hydrogel with tunable crosslinking degree in vivo is important for tissue engineering.Herein,we present a dual crosslinking strategy to prepare injectable hydrogels with step-by-step tunable crosslinking degree using Schiff base reaction and photopolymerization.The developed hyaluronic acid/poly(y-glutamic acid)(HA/y-PGA)hydrogels exhibit step-by-step tunable swelling behavior,enzymatic degradation behavior and mechanical properties.Mechanical performance tests show that the storage moduli of HA/y-PGA hydrogels are all less than 2000 Pa and the compressive moduli are in kilopascal,which have a good match with soft tissue.In addition,NIH 3T3 cells encapsulated in HA/y-PGA hydrogel exhibit a high cell viability,indicating a good cytocompatibility of HA/y-PGA hydrogel.Therefore,the developed HA/y-PGA hydrogel as an injectable biomaterial has a good potential in soft tissue engineering.
文摘The present studies were conducted to compose an injectable solution of colistin sulfate containing local anaesthesia, antioxidant and other additions. Results showed that the novel preparation was stable either to heat or to light. The term of validity of the preparation was 2 years at room temperature.The preparation containing 25. 0 mg ml-1 colistin sulfate showed no local tissue irritation, but the concentration of 50. 0 mg ml-1 colistin sulfate showed obvious local tissue irritation. Result of acute toxicity test showed that the LD50 of intramuscular injection in mice was 38. 72 mg kg-1, and oral LD50 was 431. 39 mg kg-1. The evidence of neurotoxicity was observed in mice in the acute toxicity test. A dose of 10.0 mg kg-1 b. w. or 15:0 mg kg-1b. w. was administered intramuscularly to piglet once daily for 5 days. No changes were detected in the piglet body except for the slight epithelial tissue's granular degenerations in the kidney and liver at the dose of the 10.0 mg kg-1. While at the dose of 15. 0 mg kg-1, the obvious neurotoxicity was observed at 4-5 days. The epithelial tissues in the kidney and liver showed moderate granular degenerations, especially in the tubuli renales cells. Blood cell's morphosis indexes were normal. With relation to liver's function, the indexes went beyond the normal scope. But with relation to kidney's function, the indexes showed mostly normal.When the preparation was separately administered into muscle(i. m.) in piglets with the dose of 2. 5 and 5. 0 mg kg-1 b. w, whose Cmax were 3.73±0. 28 and 6. 40±0.18 Abstract:g ml-1; Tmax were 32±1. 5 and 34±1.8min; t1/2β were 256±14 min and 264±29 min, respectively. t1/2βt was 251±13 min for the injection given into aural vein( i. v.) with the dose of 2.5 mg kg1-1 b. w.. Samples of the experimentally determined plasma concentration of colistin sulfate generated two-exponential model with first-order absorption. The mean absolute bioavail-ability coefficient of 2.5 and 5. 0 mg kg-1 b. w. (i. m.) were 98. 30 and 88. 54%, respectively. The high bio-availability and the long maintaining time of the valid blood-drug concentration showed that the injectable solution was suitable for i. m. in pigs, whose recommended dose was 2.5 mg kg-1 b. w. , twice daily.
文摘Aim： To report our experience with penile girth augmentation using liquid injectable silicone. Methods： Between August 2003 and July 2006, 324 men （mean age 35 years, range 19-65 years） received a series of liquid silicone subcutaneous injections between the penile skin and the corpora cavernosa on the dorsal and lateral aspects of the penile shaft, under local anesthesia. Digital photographs taken pre- and post-procedure （n = 324）, and penile contour measurements （n = 30） yielded objective results. Subjective results were derived from patient and partner testimony of satisfaction. Follow-up averaged 20 months （range 1-36 months）. Results： Three hundred and twenty-four procedures were primary augmentations. Most men （61%） were married, 7% were accompanied by their partners, and 93% were circumcised. The mean measured penile circumference was 9.5 cm （7.5-11.5 cm） pretreatment and 12.1 cm （10.3-15.3 cm） post-treatment （mean increase of 27% in circumference and 0.84 cm in diameter）. Patient and partner satisfaction was already expressed after the first two treatments. Sexual activity could be resumed after 8 h. Complications （mild bruising） were easily resolved. Conclusion： Penile girth augmentation using liquid injectable silicone yields very satisfactory short-term results with no immediate or short-term complications.
基金supported by the National Key Research and Development Program of China(No.2017YFC1104102)National Natural Science Foundation of China(Nos.31370958,21875044)+1 种基金Key Program of Natural Science Foundation of Fujian Province(No.2018Y0056)the International Scientific Partnership Program ISPP at King Saud University for funding this research work through ISPP-17-94(2)。
文摘Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self-healing nano hybrid hydrogel was on-demand prepared via a fast(within 30 s)and easy gelation approach by reversible Schiff base formed between-CH=O of oxidized sodium alginate(OSA)and-NH2 of glycol chitosan(GCS)mixed with calcium phosphate nanoparticles(CaP NPs).Its raw materials can be ready in large quantities by a simple synthesis process.The mechanical strength,degradation and swelling behavior of the hydrogel can be readily controlled by simply controlling the molar ratio of-CH=O and-NH2.This hydrogel exhibits pH responsiveness,good degradability and biocompatibility.The hydrogel used as the matrix for mesenchymal stem cells can significantly induce the proliferation,differentiation and osteoinduction in vitro.These results showed this novel hydrogel is an ideal candidate for applications in bone tissue regeneration and drug delivery.
基金the National Natural Science Foundation of China (Nos. 21432004,21672113 and 91527301)for financial support
文摘A luminescent and injectable supramolecular hydrogel was successfully constructed through the non- covalent cross-linking of polymers mediated by tetraphenylethylene-bridged cyclodextrin oligomers, presenting the strong blue fluorescence, the reversible gelation behavior responsive to various external stimuli and the good mechanical property of shear thinning.
基金This work was financially sponsored by the National Natural Science Foundation of China(Nos.81971622,81671696,82071938,and 51703141)Sichuan Science and Technology Program(Nos.2019YFS0219,2020YFH0087,and 2020YJ0055)the Post-Doctor Research Project,West China Hospital,Sichuan University(No.2018HXBH077).
文摘The increasing incidence of osteoarthritis(OA) seriously affects life quality,posing a huge socioeco nomic burden.Tissue engineering technology has become a hot topic in articular cartilage repair as one of the key treatment methods to alleviate OA.Hydrogel,one of the most commonly used scaffold materials,ca n provide a good extracellular matrix microenvironment fo r seed cells such as bone marrow mesenchymal stem cells(BMSCs),which can promote cartilage regeneration.However,the low homing rate of stem cells severely limits their role in promoting articular cartilage regeneration.Stro mal cell-derived factor-1α(SDF-1α) plays a crucial role in the activatio n,mobilization,homing,and migration of MSCs.He rein,a novel injectable chemotaxis hydrogel,composed of chitosan-based injectable hydrogel and embedding SDF-1α-loaded nanodroplets(PFP@NDs-PEG-SDF-1α) was designed and fabricated.The ultrasound was then used to augment the injectable chemotaxis hydrogel and promote the homing migration of BMSCs for OA cartilage repair.The effect of ultrasound augmenting injectable PFP@NDs-PEG-SDF-1α/hydrogel on the migration of BMSCs was verified in vitro and in vivo,which re markably promotes stem cell homing and the repair of cartilage in the OA model.Therefore,the treatment strategy of ultrasound augmenting injectable chemotaxis hydrogel has a bright potential for OA articular cartilage repair.
文摘BACKGROUND Given the low survival rate in pancreatic cancer,new therapeutic techniques have been explored,especially for unresectable or borderline resectable disease.Endoscopic ultrasound(EUS)provides real-time imaging and minimally invasive access for local and targeted injection of anti-tumor agents directly into the pancreatic tumor.Limited studies have been reported using this technique for the treatment of pancreatic ductal adenocarcinoma(PDAC).AIM To evaluate the progress made with EUS-guided injectable therapies in the treatment of PDAC.METHODS All original articles published in English until July 15,2021,were retrieved via a library-assisted literature search from Ovid Evidence-Based Medicine Reviews and Scopus databases.Reference lists were reviewed to identify additional relevant articles.Prospective clinical studies evaluating the use of EUS-guided injectable therapies in PDAC were included.Studies primarily directed at non-EUS injectable therapies and other malignancies were excluded.Retrieved manuscripts were reviewed descriptively with on critical appraisal of published studies based on their methods and outcome measures such as safety,feasibility,and effectiveness in terms of tumor response and survival.Heterogeneity in data outcomes and therapeutic techniques limited the ability to perform comparative statistical analysis.RESULTS A total of thirteen articles(503 patients)were found eligible for inclusion.The EUS-injectable therapies used were heterogeneous among the studies consisting of immunotherapy(n=5)in 59 patients,chemotherapy(n=1)in 36 patients,and viral and other biological therapies(n=7)in 408 patients.Eleven of the studies reviewed were single armed while two were double armed with one randomized trial and one non-randomized comparative study.Overall,the included studies demonstrated EUS-guided injectable therapies to be safe and feasible with different agents as monotherapy or in conjunction with other modalities.Promising results were also observed regarding their efficacy and survival parameters in patients with PDAC.CONCLUSION EUS-guided injectable therapies,including immunotherapy,chemotherapy,and viral or other biological therapies have shown minimal adverse events and potential efficacy in the treatment of PDAC.Comparative studies,including controlled trials,are required to confirm these results in order to offer novel EUS-based treatment options for patients with PDAC.
基金National Natural Science Foundation of China(Nos.22131008 and 21971127)the Haihe Laboratory of Sustainable Chemical Transformations for financial support.
文摘Implantable system maximizes drug concentration and continuously releases drugs near the tumor,which is an effective tool to solve the difficult retention of chemotherapy drugs in bladder cancer.In this work,a novel polysaccharide supramolecular injectable hydrogel(CCA hydrogels for short)is rapidly constructed by simply mixing cationic chitosan,anionic sulfobutyl etherβ-cyclodextrin(SBE-β-CD)and a trace amount of silver ions.The injected hydrogel reconstituted and regained its shape in less than 1 h,and it can still maintain the elasticity suitable for the human body.By packaging the drug directly,the gel achieves a high concentration of doxorubicin,an anticancer drug.Using MB49-luc cells as the model of bladder tumor for anti-tumor in vivo,the CCA-DOX gel has obvious inhibitory effect on bladder tumor,and its inhibitory effect is much greater than that of free DOX.Therefore,this self-healing injectable hydrogel has great potential for in situ treatment of bladder cancer.
文摘Background: There is a large assortment of modalities for the surgical treatment/management of distal radius fractures (DRFs), where the most widely used is the fixed-angle volar plating (VLP) system, which, sometimes, is referred to as the “surgical modality of choice”. While outcomes with each modality are usually good to excellent, each has its share of shortcomings and complications. Thus, there is scope for improvements to existing modalities and/or introduction of new ones. Study Purpose: We introduce a novel modality, namely, the prototype of an intramedullary injectable bioresorbable polymer-bioresorbable balloon osteosynthesis (IPBO) system, and investigated its plausibility. Experimental Procedures: The biomechanical performance of a construct comprising a synthetic distal radius (fourth-generation Sawbones?) on which a simulated fracture was created (4-mm wide osteotomy positioned 25 mm from the most distal end of the radius) and fixated with a placement of the IPBO system (SIPBO Construct) was compared to that when the fixation was with an approved Ti-6Al-4V alloy VLP system (SVLP Construct), under a clinically-relevant compressive loading protocol. Performance involved determination of quantitative parameters of the construct (initial longitudinal stiffness (ICLS), final longitudinal stiffness (FCLS), and load-to-failure (Pf)) and observation and recording of features of the construct at the fracture point. We also determined the quantitative parameters for the intact synthetic distal radius (control). Results: For each of the quantitative parameters, the range of values for SIPBO Construct was within that for SVLP Construct, suggesting that the IPBO System is a plausible modality. Also, for SIPBO Construct, failure occurred within the polymer zone, whereas, for SVLP Construct, some failure features were fracture of the cortical wall and of the dorsal proximal fragments. Conclusion: The findings suggest that the IPBO system is plausible. As such, it merits further study;for example, determination of the influence of fracture gap fill ratio (defined as the proportion of the fracture gap that is filled by the expanding balloon as the polymer is injected into the balloon) on a large collection of quantitative biomechanical parameters.
文摘BACKGROUND Collagen membrane and platelet-rich fibrin(PRF)have emerged as vital biomaterials in the field of periodontal regeneration.Minimally invasive techniques are being preferred by most periodontists,as it is patient compliant with fewer post-surgical complications as compared to conventional surgical techniques.Thus,in this study we have evaluated the effect of injectable PRF(i-PRF)with collagen membrane compared with collagen membrane alone using vestibular incision subperiosteal tunnel access(VISTA)technique for gingival recession coverage.AIM To compare the efficacy of VISTA using collagen membrane with collagen membrane soaked in injectable PRF for gingival recession coverage.METHODS A split mouth randomized controlled clinical trial was designed;13 subjects having at least 2 teeth indicated for recession coverage were enrolled in this study.The sites were randomly assigned to control group(VISTA using collagen membrane alone)and the test group(VISTA using collagen membrane with i-PRF).The clinical parameters assessed were pocket depth,recession depth(RD),recession width(RW),relative attachment level,keratinised tissue width(KTW),keratinised tissue thickness(KTT),and percentage root coverage.RESULTS RD showed a statistically significant difference between the test group at 3 mo(0.5±0.513)and 6 mo(0.9±0.641)and the control group at 3 mo(0.95±0.51)and 6 mo(1.5±0.571),with P values of 0.008 and 0.04,respectively.RW also showed a statistically significant difference between the test group at 3 mo(1±1.026)and 6 mo(1.65±1.04)and the control group at 3 mo(1.85±0.875)and 6 mo(2.25±0.759),with P values of 0.008 and 0.001,respectively.Results for KTW showed statistically significant results between the test group at 1 mo(2.85±0.489),3 mo(3.5±0.513),and 6 mo(3.4±0.598)and the control group at 1 mo(2.45±0.605),3 mo(2.9±0.447),and 6 mo(2.75±0.444),with P values of 0.04,0.004,and 0.003,respectively.Results for KTT also showed statistically significant results between test group at 1 mo(2.69±0.233),3 mo(2.53±0.212),and 6 mo(2.46±0.252)and the control group at 1 mo(2.12±0.193),3 mo(2.02±0.18),and 6 mo(1.91±0.166),with P values of 0.001,0.001,and 0.001,respectively.The test group showed 91.6%,81.6%,and 67%root coverage at 1 mo,3 mo,and 6 mo,while the control group showed 82.3%,66.4%,and 53.95%of root coverage at 1 mo,3 mo,and 6 mo,respectively.CONCLUSION The use of minimally invasive VISTA technique along with collagen membrane and injectable form of platelet-rich fibrin can be successfully used as a treatment method for multiple or isolated gingival recessions of Miller’s class-I and class-II defects.
