Study on Preparation of Temperature-sensitive Injectable Hydrogel

To get a sort of new scaffold material for soft tissue reconstruction,we have prepared XLHA-PNIPAAm and XLHA-MC injectable hydrogels through blending crosslinked HA(XLHA) and two temperature-sensitive materials differed in degradation poly(N-isopropylacrylamide)(PNIPAAm) and methylcellulose(MC),respectively.We tested the injectablility,enzymatic biodegradability,temperature-sensitivity,structure cytotoxicity and hemolysis of the two injectable hydrogels.Our research has successfully obtained the preparation condition of XLHA-PNIPAAm injectable hydrogel,and verified that adding non-degradable material PNIPAAm can postpone the degradation of HA more effectively than degradable material MC.PNIPAAm prepared with 5 kGy dose radiation,MBAAm/NIPAAm(M/M)=0.015,monomer concentration=3% produced XLHA-PNIPAAm with slowest enzymatic biodegradability.DSC results showed that temperature-sensitivity of the XLHA-PNIPAAm was more stable than that of XLHA-MC.Two composite hydrogels were qualified in cytotoxicity and hemolysis tests and the biocompatibility of XLHA-PNIPAAm hydrogel showed better than XLHA-MC hydrogel.

Injectable Self‑Healing Adhesive pH‑Responsive Hydrogels Accelerate Gastric Hemostasis and Wound Healing

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.

Intratympanic injection of hydrogel nanodrug for the prevention and treatment of sensorineural hearing loss

Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.

Bioinspired Injectable Self-Healing Hydrogel Sealant with Fault-Tolerant and Repeated Thermo-Responsive Adhesion for Sutureless Post-Wound-Closure and Wound Healing

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.

Injectable <i>in situ</i>crosslinkable hyaluronan-polyvinyl phosphonic acid hydrogels for bone engineering

A novel injectable hydrogel that was synthesized by in situ crosslinking of hyaluronan and polyvinyl phosphonic acid was proposed in this study. Fourier transform infrared spectrum (FT-IR) analysis, scanning electron microscope (SEM), pH measurement, and biodegradation test were used to confirm its characteristics. The results permitted to prove successful crosslinking, observe the inner morphology of hydrogel and pore sizes distribution, and determine the decomposition of hydrogel components during incubation time. Result of pH measurement showed that the pH scale of hydrogel decreased when volume of PVPA increased. As a consequence, it affected the cytotoxicity value, cell proliferation, and cell growth behaviors of each hydrogel. Optical microscope observation showed that chondroblasts cell proliferated well on HA-PVPA hydrogel. Therefore, these results suggest that the new injectable hydrogel is appropriate for bone/cartilage regeneration applications.

Finite deformation swelling of a temperature-sensitive hydrogel cylinder under combined extension-torsion

The swelling behavior of a temperature-sensitive poly-N-isopropylacrylamide(PNIPAM) hydrogel circular cylinder is studied subjected to combined extension-torsion and varied temperature. In this regard, a semi-analytical solution is proposed for general combined loading. A finite element(FE) analysis is conducted, subjecting a hydrogel cylinder to the combined extension-torsion and the varied temperature to evaluate the validity and accuracy of the solution. A user-defined UHYPER subroutine is developed and verified under free and constrained swelling conditions. The FE results illustrate excellent agreement with the semi-analytical solution. Due to the complexity of the problem, some compositions and applied loading factors are analyzed. It is revealed that for larger cross-linked density and larger ending temperature, the cylinder yields higher stresses and smaller radial swelling deformation. Besides, the radial and hoop stresses increase by applying larger twist and axial stretch. The hoop stresses intersect at approximately R/Rout = 0.58, where the hoop stress vanishes. Besides, the axial force has direct and inverse relationships with the axial stretch and the twist, respectively. However, the resultant torsional moment behavior is complex, and the position of the maximum point varies significantly by altering the axial stretch and the twist.

Preparation and Evaluation of an Injectable Chitosan-Hyaluronic Acid hydrogel for Peripheral Nerve Regeneration

The aim of this study was to obtain the fillers in the lumen of hollow nerve conduits（NCs） to improve the microenvironment of nerve regeneration. A p H-induced injectable chitosan（CS）-hyaluronic acid（HA） hydrogel for nerve growth factor（NGF） sustained release was developed. Its properties were characterized by gelation time, FT-IR, SEM, in vitro swelling and degradation. Furthermore, the in vitro NGF release profiles and cell biocompatibility were also investigated. The experimental results show that the CS-HA aqueous solution can undergo a rapid gelation 3 minutes after its environmental p H is changed to 7.4. The CSHA hydrogel has interconnected channels with a controllable pore diameter and with a porosity of about 80%. It has a favorable swelling behavior and can be degraded by about 70% within 8 weeks in vitro and is suitable for NGF release. The CS-HA/NGF hydrogel exhibits a lower cytotoxicity and is in favor of the adhesion and proliferation of the BMMSCs cells. It is indicated that the CS-HA/NGF will be a promising candidate for neural tissue engineering.

An injectable,self-healable,and reusable PEDOT:PSS/PVA hydrogel patch electrode for epidermal electronics

Injectability empowers conductive hydrogels to transcend traditional limitations,unlocking a realm of possibilities for innovative medical,wearable,and therapeutic applications that can significantly enhance patient care and quality of life.Here,we report an injectable,self-healable,and reusable hydrogel obtained by mixing the concentrated poly(3,4-ethylenedioxythiophene)doped with polystyrene sulfonate(PEDOT:PSS)suspension(~2 wt.%solid content),polyvinyl alcohol(PVA),and borax.Leveraging the presence of reversible borax/hydroxyl bonds and multiple hydrogen bonds,this PEDOT:PSS/PVA hydrogel exhibits notable shear-thinning behavior and self-healing capabilities,enabling it to be injected as a gel fiber from a syringe.As-prepared injectable hydrogel also demonstrates an ultra-low modulus(~2.5 MPa),reduced on-skin impedance(~45%of commercial electrodes),and high signal-to-noise ratio(SNR)(~15-22 dB)in recording of electrocardiography(ECG),electromyography(EMG),and electroencephalogram(EEG)signals.Furthermore,the injectable hydrogels can be remolded and reinjected as the reusable electrodes,maintaining nearly identical electrophysiological recording capabilities and brain-computer interface(BCI)performance compared to commercial wet electrodes.With their straightforward fabrication,excellent material properties and electronic performance,ease of cleaning,and remarkable reusability,our injectable PEDOT:PSS/PVA hydrogels hold promise for advancements in BCI based electronics and wearable bioelectronics.

Polysaccharide based supramolecular injectable hydrogels for in situ treatment of bladder cancer

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.

Injectable“cocktail”hydrogel with dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic effect

The combination of the first-line standard chemotherapeutic drug doxorubicin hydrochloride(DOX)and the molecular-targeted drug Herceptin(HCT)has emerged as a promising strategy for human epidermal growth receptor 2(HER-2)overexpressing breast cancer treatment.However,insufficient drug accumulation and severe cardiotoxicity are two major challenges that limit its clinical application.Herein,an in situ forming gold nanorods(AuNRs)-sodium alginate(ALG)hybrid hydrogel encapsulating DOX and HCT was engineered for tumor synergistic therapy involving injectable,dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic therapy.The photothermal agent AuNRs,anticancer drug DOX,and anticancer antibody HCT were mixed in ALG solution,and after injection,the soluble ALG was quickly transformed into a hydrogel in the presence of Ca^(2+)in the body.Significantly,the hybrid hydrogel exhibits an extremely high photothermal conversion efficiency of 70%under 808 nm laser irradiation.The thermal effect can also provide photothermal stimulation to trigger the drug release from the gel matrix.In addition,the drug release rate and the releasing degree are also sensitive to the pH.In vitro studies demonstrated that the PEI-AuNR/DOX/HCT/ALG hydrogel has facilitated the therapeutic efficiency of each payload and demonstrated a strong synergistic killing effect on SK-BR-3 cells.In vivo imaging results showed that the local drug delivery system can effectively reduce the nonspecific distribution in normal tissues and increase drug concentration at tumor sites.The proposed hydrogel system shows significant clinical implications by easily introducing a sustainable photothermal therapy and a potential universal carrier for the local delivery of multiple drugs to overcome the challenges faced in HER-2 overexpressing cancer therapy.

Preparation of Thermosensitive Chitosan Formulations Containing 5-Fluorouracil/Poly-3-hydroxybutyrate Microparticles Used as Injectable Drug Delivery System

The auto-gelling and drug release properties of the thermosensitive chitosan-β-glycerophosphate for- mulation 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 profiles 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 first 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. This 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.

携川芎嗪超分子导电水凝胶表征分析及对脊髓损伤大鼠的修复作用

背景:基于医工结合理念和中医药治疗的优势,将中药有效活性成分单体负载于组织工程材料构建新型复合材料在损伤局部递送药物,是修复脊髓损伤的研究热点,有望成为解决这一难题的有效手段。目的:观察携川芎嗪超分子导电水凝胶修复大鼠脊髓损伤的效果。方法:制备携川芎嗪超分子导电水凝胶,表征其微观结构、电导率、流变性、溶胀率及体外缓释性能。采用随机数字表法将45只SD大鼠分为3组,每组15只:假手术组不损伤脊髓,模型组建立脊髓损伤模型,水凝胶组建立脊髓损伤模型后向脊髓损伤区域注射携川芎嗪超分子导电水凝胶。造模前及造模后1,7,14,21,28 d,采用BBB评分评估大鼠后肢运动功能恢复情况;造模后28 d取损伤处脊髓组织,分别进行苏木精-伊红染色、免疫组化染色及Western blot检测。结果与结论:①扫描电镜下可见,携川芎嗪超分子导电水凝胶呈现出三维微米尺度的多孔网络结构,具有较高的孔隙率,孔径约为100μm;该水凝胶的电导率为7.66 S/m、溶胀率为3764.42%,具备一定的力学稳定性能,同时具有可注射性;体外缓释实验显示,携川芎嗪超分子导电水凝胶可持续释放川芎嗪达800 h以上,且随着时间延长,药物累计释放量呈上升趋势。②随着造模时间的延长,模型组、导电水凝胶组大鼠后肢运动功能逐渐恢复,水凝胶组造模后14,21,28 d的后肢运动功能优于模型组(P<0.05)。苏木精-伊红染色显示,模型组脊髓组织出现空洞,残端可见大量炎性细胞浸润;水凝胶组脊髓损伤区可见部分炎性细胞浸润,损伤区域空洞面积缩小,交接区出现神经元细胞,组织排列较为整齐。免疫组化染色及Western blot检测显示,水凝胶组大鼠脊髓组织中肿瘤坏死因子α、白细胞介素6蛋白表达低于模型组(P<0.05),神经元核抗原蛋白表达高于模型组(P<0.05)。③结果显示,携川芎嗪超分子导电水凝胶可促进损伤脊髓组织的修复。

中医药联合医用水凝胶治疗疾病的策略及意义

背景:医用水凝胶是具有三维结构网络的新型功能高分子材料,具有出色的生物相容性,目前已在组织工程领域、药物载体领域有广泛研究,但基于组织工程探究医用水凝胶与中医药结合治疗疾病的研究还处于初期探索阶段。因此,通过对医用水凝胶机制作用的剖析,整合医用水凝胶与中医药在研究中联合应用的文章,进而更好地为科研工作者提供思路,对中医药与医用水凝胶联合应用具有重要意义。目的:基于组织工程研究探讨中医药联合医用水凝胶治疗疾病的策略及意义。方法:利用PubMed和中国知网数据库,检索有关中医药联合医用水凝胶在组织工程中应用的文献,检索时间为2010年1月至2022年11月,英文检索词为“hydrogel,traditional Chinese medicine,drug carrier,tissue engineering”,中文检索词为“医用水凝胶、中医药、药物载体、组织工程”。根据纳入与排除标准对所有文章进行初筛后,最终纳入61篇文章进行综述。结果与结论:①中医药联合医用水凝胶的应用虽然在关节内、组织器官内、软组织伤口和组织工程等方面有所涉及,但除了中医药结合水凝胶敷料在临床应用治疗软组织损伤外,其他方面尚处于基础实验阶段。②中医药联合医用水凝胶的发展有着巨大潜力和发展前景,但对于性能要求较高的凝胶在制造方面存在一定难度,理化性质精确掌握难度较大。③目前综合来看可注射水凝胶凭借着简便易用的特点,其在与中医药联合使用可延伸范围较广,可用于关节、器官和组织工程相关疾病的治疗;智能水凝胶有较高的灵敏度和可逆转化性也可满足特殊环境下的使用;将两者结合的中医药使用过程中还需要明确中药成分的作用机制。④中医药联合医用水凝胶治疗疾病的策略应着手于中医药对器官、组织、细胞的治疗作用联合适当种类的医用水凝胶进行匹配,可弥补传统中医给药方式和频繁给药的不足,在组织工程方面可以用水凝胶负载中药干预后的干细胞,或者同时负载中药和干细胞用于相关疾病的治疗。⑤在中医药联合医用水凝胶应用的未来研究中,还需要考虑:应当确保医用水凝胶生物性能可以量化,以不同材料不同制造工艺把握水凝胶特性,制造出所需要的符合应用条件的医用水凝胶;在中医药方面需要对已知中药单体、中药复方提取物的治疗效果和应用机制全面了解剖析,在更明了的机制下实现中医药与医用水凝胶更多更完美的结合;借助医学科技创新能力的不断提高,医用水凝胶可以创新性地结合中医药其他传统治疗方法比如针灸、推拿和拔罐等方式进行多角度运用。

多糖基温敏可注射型水凝胶的研究与应用进展

多糖基温敏可注射型水凝胶作为一类智能软物质材料,在不同温度的刺激下能够实现液态溶胶-固态凝胶的可逆转变,具有生物相容性高、生物降解性强及物理和化学特性可调控等优势,在生物医学领域受到了广泛关注。该文概括了温敏可注射型水凝胶的溶胶-凝胶相转变机理;阐述了设计与合成多糖基温敏可注射型水凝胶的策略,包括小分子基团修饰多糖、合成型温敏聚合物接枝多糖、添加剂改性多糖;综述了多糖基温敏可注射型水凝胶在伤口愈合、药物递送和软骨修复生物医学领域中的应用,并对该领域存在的优化原料组成及设计策略、开发多样化环境刺激响应、增强机械强度和稳定性三方面的挑战提出建议;最后,对拓展多糖基水凝胶产品应用范围、加速推进其大范围临床应用进行了展望。

基于壳聚糖/银离子的可逆温敏水凝胶的制备与性能

以壳聚糖(CS)和AgNO_(3)为主要原料,通过CS与Ag^(+)的超分子络合作用制备了一系列可逆温敏CS-Ag水凝胶,采用FTIR、XRD、XPS、SEM和EDS对CS-Ag水凝胶的结构和化学状态进行了表征。结果表明,通过同时调节AgNO_(3)用量和体系pH可制备具有相同凝胶温度的CS-Ag水凝胶。当CS用量为0.60 g、AgNO_(3)用量为0.19 g、体系总体积为21 mL、保持水凝胶pH=4.24时,制备的CS-Ag-19水凝胶凝胶温度为50℃,具有最佳的热可逆性能,至少可循环相变5次,具有室温避光保存5个月的稳定性,并表现出对大肠杆菌良好的抗菌性能。CS-Ag-19的溶胶-凝胶转换是由CS的氨基在不同温度下的超分子相互作用控制,H^(+)和Ag^(+)在温度、浓度变化的驱动下,对游离氨基的竞争反应(质子化和络合作用)之间的平衡关系使水凝胶具有温敏可逆性。CS-Ag-19水凝胶的可注射和温敏凝胶性能使其具有作为水凝胶抗菌敷料的应用潜力。

可注射海藻酸钠水凝胶的制备及应用

背景:天然来源的多糖海藻酸钠具有含量高、成本低、生物相容性好、生物可降解性好等特点,在可注射型水凝胶的生产中得到了广泛应用,成为制备可注射水凝胶的理想原料之一。目的:就海藻酸钠的性质、可注射海藻酸钠水凝胶的制备及其在组织工程中的应用进展进行综述。方法:利用计算机检索Web of Science、PubMed、中国知网等数据库,中文检索词为“海藻酸钠;水凝胶;可注射”,英文检索词为“alginate;hydrogel;inject*”,检索文献时间范围为2017年6月至2022年6月。结果与结论:由于海藻酸钠来源广泛,分子链结构上存在着许多可改性基团,可用各种共价交联或非共价交联的方法合成多种性能优良的可注射型水凝胶;将其他具有生物功能的分子引入海藻酸钠水凝胶中,可以调节其功能、拓宽其应用范围。另外,由于生物相容性和生物可降解性等优良的物理化学特性,可注射型海藻酸钠水凝胶在生物医学方面有着广泛的发展潜力,海藻酸钠水凝胶在体外与各种药物、细胞、因子或其他生物作用分子均匀调配,在人体内可形成凝胶,在基因载体、细胞支架和创口修复中起着举足轻重的作用。

壳聚糖基可注射水凝胶在骨组织修复再生方面的研究进展

骨移植物或骨替代材料已经被广泛应用于骨疾病相关的治疗手术。传统的骨修复方法包括自体移植、同种异体移植和手术重建,但是往往会带来排异反应、疾病传播风险和重复手术的潜在危害,因此利用组织工程技术对临床治疗骨缺损相关疾病具有重要的研究意义。骨组织工程是一个涉及多学科交叉的领域,在生物医用方面具有重要的应用价值,壳聚糖是天然高分子的一种典型代表,具有良好的生物安全性、抗菌性、抗氧化,以及低毒性及低成本等特点,被认为是组织再生领域中重要的骨修复材料。因此,基于壳聚糖的可注射水凝胶能够均匀填充不规则骨缺损,当与其他聚合物或生物活性成分相结合后已被证明是自体骨移植物的有效替代品。本综述将重点介绍壳聚糖基可注射水凝胶的制备方法、理化性质及其在骨再生中的发展现状,总结骨组织工程面临的困难挑战和未来的研究发展方向,为研发新一代组织工程支架材料用于骨缺损修复的治疗提供新思路。

Promoting lacunar bone regeneration with an injectable hydrogel adaptive to the microenvironment

Injectable hydrogel is suitable for the repair of lacunar bone deficiency.This study fabricated an injectable,self-adaptive silk fibroin/mesoporous bioglass/sodium alginate(SMS)composite hydrogel system.With controllable and adjustable physical and chemical properties,the SMS hydrogel could be easily optimized adaptively to different clinical applications.The SMS hydrogel effectively showed great injectability and shapeability,allowing defect filling with no gap.Moreover,the SMS hydrogel displayed self-adaptability in mechanical reinforcement and degradation,responsive to the concentration of Ca2+and inflammatory-like pH value in the microenvi-ronment of bone deficiency,respectively.In vitro biological studies indicated that SMS hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells by activation of the MAPK signaling pathway.The SMS hydrogel also could improve migration and tube formation of human umbilical vein endothelial cells.Investigations of the crosstalk between osteoblasts and macrophages confirmed that SMS hydrogel could regulate macrophage polarization from M1 to M2,which could create a specific favorable environment to induce new bone formation and angiogenesis.Meanwhile,SMS hydrogel was proved to be antibacterial,especially for gram-negative bacteria.Furthermore,in vivo study indicated that SMS could be easily applied for maxillary sinus elevation,inducing sufficient new bone formation.Thus,it is convincing that SMS hydrogel could be potent in a simple,minimally invasive and efficient treatment for the repair of lacunar bone deficiency.

An injectable conductive hydrogel restores electrical transmission at myocardial infarct site to preserve cardiac function and enhance repair

Myocardial infarction(MI)leads to massive cardiomyocyte death and deposition of collagen fibers.This fibrous tissue disrupts electrical signaling in the myocardium,leading to cardiac systolic and diastolic dysfunction,as well as arrhythmias.Conductive hydrogels are a promising therapeutic strategy for MI.Here,we prepared a highly water-soluble conductive material(GP)by grafting polypyrrole(PPy)onto non-conductive gelatin.This component was added to the gel system formed by the Schiff base reaction between oxidized xanthan gum(OXG)and gelatin to construct an injectable conductive hydrogel.The prepared self-healing OGGP3(3 wt%GP)hydrogel had good biocompatibility,elastic modulus,and electrical conductivity that matched the natural heart.The prepared biomaterials were injected into the rat myocardial scar tissue 2 days after MI.We found that the cardiac function of the rats treated with OGGP3 was improved,making it more difficult to induce arrhythmias.The electrical resistivity of myocardial fibrous tissue was reduced,and the conduction velocity of myocardial tissue was increased.Histological analysis showed reduced infarct size,increased left ventricular wall thickness,increased vessel density,and decreased inflammatory response in the infarcted area.Our findings clearly demonstrate that the OGGP3 hydrogel attenuates ventricular remodeling and inhibits infarct dilation,thus showing its potential for the treatment of MI.

Natural biopolymers derived hydrogels with injectable,self-healing,and tissue adhesive abilities for wound healing

Developing a biocompatible and multifunctional adhesive hydrogel with injectability and self-healing ability for promoting wound healing is highly anticipated in various clinical applications.In this paper,we present a novel natural biopolymer-derived hydrogel based on the aldehyde-modified oxidized guar gum(OGG)and the carboxymethyl chitosan(CMCS)for efficiently improving wound healing with the encapsulation of vascular endothelial growth factor(VEGF).As the hydrogels are synthesized via the dynamically reversible Schiff base linkages,it is imparted with excellent self-healing ability and good shear thinning behavior,which make the hydrogel be easily and conveniently injected through a needle.Besides,the physiochemical properties,including porous structure,mechanical strength and swelling ratio of the hydrogel can be well controlled by regulating the concentrations of the OGG.Moreover,the hydrogel can attain strong adhesion to the tissues at physiological temperature based on the Schiff base between the aldehyde group on the hydrogel and the amino group on the tissue.Based on these features,we have demonstrated that the VEGF encapsulated hydrogel can adhere tightly to the defect tissue and improve wound repair in the rat model of defected skin by promoting cell proliferation,angiogenesis,and collagen secretion.These results indicate that the multifunctional hydrogel is with great scientific significance and broad clinical application prospects.