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A self-fused hydrogel for the treatment of glottic insufficiency through outstanding durability,extracellular matrix-inducing bioactivity and function preservation

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Bioactive Materials 2023年第6期24卷 54-68页

作者： Chen-Yu Zou Juan-Juan Hu Dan Lu Qian-Jin Li Yan-Lin Jiang Rui Wang Hai-Yang Wang Xiong-Xin Lei Jesse Li-Ling Hui Yang Hui-Qi Xie Laboratory of Stem Cell and Tissue Engineering Orthopedic Research InstituteMed-X Center for MaterialsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041PR China Department of Otolaryngology Head and Neck SurgeryWest China HospitalSichuan UniversityChengduSichuan610041PR China Department of Medical Genetics West China Second HospitalSichuan UniversityChengduSichuan610041PR China

Injection laryngoplasty with biomaterials is an effective technique to treat glottic insufficiency.However,the inadequate durability,deficient pro-secretion of extracellular matrix(ECM)and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic effect.Herein,a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism(photo-triggered and dynamic covalent bonds).Owing to its characteristic networks,the synergistic effect of the hydrogel for vocal folds(VFs)vibration and phonation is adequately demonstrated.Notably,owing to its inherent bioactivity of polysaccharides,the hydrogel could significantly enhance the secretion of major components(type I/III collagen and elastin)in the lamina propria of the VFs both in vivo and in vitro.In a rabbit model for glottic insufficiency,the optimized hydrogel(C1A1)has demonstrated a durability far superior to that of the commercially made hyaluronic acid(HA)Gel.More importantly,owing to the ECM-inducing bioactivity,the physiological functions of the VFs treated with the C1A1 hydrogel also outperformed that of the HA Gel,and were similar to those of the normal VFs.Taken together,through a simple-yet-effective strategy,the novel hydrogel has demonstrated outstanding durability,ECM-inducing bioactivity and physiological function preservation,therefore has an appealing clinical value for treating glottic insufficiency.

关键词： Glottic insufficiency Self-fusion hydrogel Extracellular matrix Physiological function

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Bone/cartilage targeted hydrogel: Strategies and applications

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生物活性材料(英文) 2023年第5期23卷 156-169页

作者： Hao Zhang Shunli Wu Weikai Chen Yan Hu Zhen Geng Jiacan Su Institute of Translational Medicine Shanghai UniversityShanghai200444China Musculoskeletal Organoid Research Center Shanghai UniversityShanghai200444China School of Medicine Shanghai UniversityShanghai200444China School of Environmental and Chemical Engineering Shanghai UniversityShanghai200444China

The skeletal system is responsible for weight-bearing,organ protection,and movement.Bone diseases caused by trauma,infection,and aging can seriously affect a patient’s quality of life.Bone targeted biomaterials are suitable for the treatment of bone diseases.Biomaterials with bone-targeted properties can improve drug utilization and reduce side effects.A large number of bone-targeted micro-nano materials have been developed.However,only a few studies addressed bone-targeted hydrogel.The large size of hydrogel makes it difficult to achieve systematic targeting.However,local targeted hydrogel still has significant prospects.Molecules in bone/cartilage extracellular matrix and bone cells provide binding sites for bone-targeted hydrogel.Drug delivery systems featuring microgels with targeting properties is a key construction strategy for bone-targeted hydrogel.Besides,injectable hydrogel drug depot carrying bone-targeted drugs is another strategy.In this review,we summarize the bone-targeted hydrogel through application environment,construction strategies and disease applications.We hope this article will provide a reference for the development of bone-targeted hydrogels.We also hope this article could increase awareness of bone-targeted materials.

关键词： Bone Cartilage hydrogel Target therapy Bone disease

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Non-contact optical characterization of negative pressure in hydrogel voids and microchannels

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Frontiers of Optoelectronics 2022年第1期15卷 113-120页

作者： Shihao Xu Xiaowei Liu Zehua Yu Kang Liu MOE Key Laboratory of Hydrodynamic Transients School of Power and Mechanical EngineeringWuhan UniversityWuhan 430072China Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhan 430074China

Negative pressure in water under tension,as a thermodynamic non-equilibrium state,has facilitated the emergence of inno-vative technologies on microfluidics,desalination,and thermal management.However,the lack of a simple and accurate method to measure negative pressure hinders further in-depth understanding of the properties of water in such a state.In this work,we propose a non-contact optical method to quantify the negative pressure in micron-sized water voids of a hydrogel film based on the microscale mechanical deformation of the hydrogel itself.We tested three groups of hydrogel samples with different negative pressure inside,and the obtained results fit well with the theoretical prediction.Furthermore,we demonstrated that this method can characterize the distribution of negative pressure,and can thus provide the possibility of investigation of the flow behavior of water in negative pressure.These results prove this technique to be a promising approach to characterization of water under tension and for investigation of its properties under negative pressure.

关键词： hydrogel Negative pressure Non-contact Optical

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Immunogenic hydrogel toolkit disturbing residual tumor “seeds” and pre-metastatic “soil” for inhibition of postoperative tumor recurrence and metastasis

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3383-3397页

作者： Minglu Zhou Qingting Zuo Yuan Huang Lian Li Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Tumor recurrence and metastasis is the leading cause of mortality for postoperative breast cancer patients. However, chemotherapy intervention after surgery is often unsatisfactory, because residual microtumors are difficult to target and require frequent administration. Here, an all-in-one and oncefor-all drug depot based on in situ-formed hydrogel was applied to fit the irregular surgical trauma, and enable direct contact with residual tumors and sustained drug release. Our immunological analysis after resection of orthotopic breast tumor revealed that postsurgical activation of CXCR4-CXCL12 signal exacerbated the immunosuppression and correlated with adaptive upregulation of PD-L1 in recurrent tumors. Thus, a multifunctional hydrogel toolkit was developed integrating strategies of CXCR4 inhibition,immunogenicity activation and PD-L1 blockade. Our results showed that the hydrogel toolkit not only exerted local effect on inhibiting residual tumor cell “seeds” but also resulted in abscopal effect on disturbing pre-metastatic “soil”. Furthermore, vaccine-like effect and durable antitumor memory were generated, which resisted a secondary tumor rechallenge in 100% cured mice. Strikingly, one single dose of such modality was able to eradicate recurrent tumors, completely prevent pulmonary metastasis and minimize off-target toxicity, thus providing an effective option for postoperative intervention.

关键词： hydrogel Postoperative treatment Tumor recurrence Pre-metastatic niche CXCR4 inhibition Immunotherapy Local therapy Immunogenic cell death

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Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift,postoperative wound closure and rapid healing

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Bioactive Materials 2023年第9期27卷 461-473页

作者： Xiong-Xin Lei Juan-Juan Hu Chen-Yu Zou Yan-Lin Jiang Long-Mei Zhao Xiu-Zhen Zhang Ya-Xing Li An-Ni Peng Yu-Ting Song Li-Ping Huang Jesse Li-Ling Hui-Qi Xie Department of Orthopedic Surgery and Orthopedic Research Institute Laboratory of Stem Cell and Tissue EngineeringState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuan610041China Department of Otolaryngology Head and Neck SurgeryWest China HospitalSichuan UniversityChengduSichuan610041China Institute of Biomedical Engineering and Informatics Ilmenau University of TechnologyGustav-Kirchh Off Str.298693IlmenauGermany Department of Medical Genetics West China Second HospitalSichuan UniversityChengduSichuan610041China

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

关键词： hydrogel Endoscopic submucosal dissection Mucosa uplift Tissue sealant Wound healing

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Sustained delivery of vascular endothelial growth factor mediated by bioactive methacrylic anhydride hydrogel accelerates peripheral nerve regeneration after crush injury

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Neural Regeneration Research 2022年第9期17卷 2064-2071页

作者： Wanlin Xu Yifan Wu Hao Lu Yun Zhu Jinhai Ye Wenjun Yang Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghaiChina Jiangsu Key Laboratory of Oral Diseases Department of Oral and Maxillofacial SurgeryThe Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina

Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes.Therefore,there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area.In this study,we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor.This modified gelatin exhibited good physical and chemical properties,biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells.When injected into the epineurium of crushed nerves,the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration,functional recovery and vascularization.The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves.

关键词： bioactive material controlled release crush injury hydrogel muscle function nerve regeneration peripheral nerve sciatic function index vascular endothelial growth factor vascularization

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Near-field electrospun PCL fibers/GelMA hydrogel composite dressing with controlled deferoxamine-release ability and retiform surface for diabetic wound healing

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Nano Research 2023年第1期16卷 599-612页

作者： Huiling Zhong Jun Huang Moucheng Luo Yifei Fang Xinchen Zeng Jun Wu Jianhang Du Medical Research Center The Eighth Affiliated Hospital of Sun Yat-sen UniversityShenzhen 518033China School of Biomedical Engineering Sun Yat-sen UniversityGuangzhou 510006China Institute of Biological and Medical Engineering Guangdong Academy of SciencesGuangzhou 510316China Department of Liver Surgery The Third People’s Hospital of ShenzhenShenzhen 518112China NHC Key Laboratory of Assisted Circulation Sun Yat-sen UniversityGuangzhou 510080China

Wound ulceration caused by diabetes is a typical chronic wound wherein healing the local tissue is difficult due to lack of blood vessels and tissue necrosis caused by the long-term accumulation of free radicals.Near-field electrospinning(NFES)is an innovative technology used to produce micro-nano-scaled,controllable sequencing fibers.In this study,we constructed a novel wound dressing based on the NFES polycaprolactone(PCL)fiber network and modified gelatin with methacrylic anhydride(GelMA)hydrogel to promote angiogenesis and the re-epithelialization of diabetic wounds.An angiogenic and antioxidant drug named deferoxamine(DFO)was encapsulated in a GelMA hydrogel to achieve a slow-release effect that is more suitable for chronic wounds.The cell adhesion experiment showed that the cells could attach to the fibers in the dressing group having a network of PCL fibers on the surface and grow along the direction of the fibers,which in turn,effectively regulates cell behavior from the physical structure.Additionally,the large pore size(~500μm)of the network allowed the cells to penetrate the pores and enter the surface of the hydrogel without being blocked out.Besides,the composite dressing had a notable effect on angiogenesis.Furthermore,antioxidation experiments confirmed that the DFO-loaded hydrogel exhibited antioxidant activity.Experimental animal models of diabetes showed that rats treated with the PCL-GelMA-DFO(PGD)hydrogel had faster ability of hemostasis,scab formation,and wound healing.In conclusion,the PGD hydrogel effectively promoted the repair of chronic wounds.

关键词： diabetic wound healing near field electrospinning hydrogel large pore

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A polyphenol-modified chitosan hybrid hydrogel with enhanced antimicrobial and antioxidant activities for rapid healing of diabetic wounds

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Nano Research 2023年第1期16卷 905-916页

作者： Zejun Xu Guiting Liu Li Zheng Jun Wu The State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan UniversityChengdu 610065China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-Sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration Life Science InstitutesGuangxi Medical UniversityNanning 530021China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanning 530021China Bioscience and Biomedical Engineering Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China Division of Life Science The Hong Kong University of Science and TechnologyHong Kong 999077China

High oxidative stress injury and bacterial infection are the main challenges that impair wound healing in diabetic patients.Therefore,a hydrogel with enhanced antimicrobial and antioxidant properties was developed for rapid healing of diabetic wounds.In this study,chitosan methacrylate-gallic acid(CSMA-GA)polymer with antioxidant activity,antimicrobial activity,and ultraviolet(UV)-triggered gelling properties was developed as a hydrogel precursor.Meanwhile,amphiphilic Pluronic F127 molecules were used to load hydrophobic chlorhexidine drug molecules to obtain F127/chlorhexidine nanoparticle(NP)with strong antibacterial activity.Subsequently,F127/chlorhexidine NPs were encapsulated in CSMA-GA hydrogel to further enhance its antibacterial activity.The hybrid hydrogel platform(CSMA-GA/F127/chlorhexidine(CMGFC))exhibited high antibacterial efficiency(>99.9%)and strong reactive oxygen species(ROS)scavenging ability(>80.0%),which effectively protected cells from external oxidative stress(upregulated superoxide dismutase(SOD)and glutathione/oxidized glutathione disulfide(GSH/GSSG)levels and downregulated malondialdehyde(MDA)levels).Moreover,in vivo results proved that the CMGFC hydrogel significantly reduced inflammatory responses(downregulated interleukin-6(IL-6)and upregulated interleukin-10(IL-10)levels),promoted angiogenesis(upregulated vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule-1(CD 31)levels),and wound healing(enhanced collagen deposition and tissue remodelling).Overall,the CMGFC hydrogel with enhanced antimicrobial and antioxidant properties demonstrated significant potential to enhance diabetic wound healing.

关键词： antimicrobial antioxidant diabetic wound hydrogel

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A self-healing and conductive ionic hydrogel based on polysaccharides for flexible sensors

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Chinese Journal of Chemical Engineering 2023年第1期53卷 73-82页

作者： Yufei Wang Zihao Chen Rui Chen Jie Wei Beijing Engineering Research Center for the Synthesis and Applications of Waterborne Polymers Beijing 100029China Key Laboratory of Carbon Fibers and Functional Polymers Ministry of EducationBeijing 100029China College of Materials Science and Engineering Beijing University of Chemical TechnologyBeijing 100029China

In this study,we proposed a self-healing conductive hydrogel based on polysaccharides and Li+to serve as flexible sensors.At first,the oxidized sodium alginate(OSA)was obtained through the oxidation reaction of sodium alginate(SA).Then OSA,carboxymethyl chitosan(CMC),and agarose(AGO)were dissolved in LiCl solution,respectively.Finally,the hydrogel was obtained through heating,mixing,and cooling processes.Because of the Schiff base structure and hydrogen bonding,the hydrogel demonstrates good mechanical and self-healing properties.The presence of Li+provides good conductivity for the hydrogel.In addition,we demonstrated the application of the hydrogel as the flexible sensors.It can perceive the process of pressing Morse code with the index finger as a pressure sensor and monitor sliding movement of the thumb as the strain sensor to browse the web with the mobile phone.Thus,the selfhealing conductive hydrogel may have potential applications in flexible wearable sensors.

关键词： hydrogel Self-healing Conductivity Polysaccharide Flexible sensor

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Degradable and Tunable Keratin-fibrinogen hydrogel as Controlled Release System for Skin Tissue Regeneration

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Journal of Bionic Engineering 2023年第3期20卷 1049-1059页

作者： Sung Jun Min Jae Seo Lee Haram Nah Ho-Jin Moon Sang Jin Lee Hyeon Jeong Kang Yu-Shik Hwang Il Keun Kwon Dong Nyoung Heo Department of Dentistry Graduate SchoolKyung Hee University26 Kyungheedae-RoDongdaemun-GuSeoul02447Republic of Korea Biofriends Inc 26 Kyungheedae-RoDongdaemun-GuSeoul02447Republic of Korea Department of Dental Materials School of DentistryKyung Hee University26 Kyungheedae-RoDongdaemun-GuSeoul02447Republic of Korea Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology School of DentistryKyung Hee UniversitySeoul02447Korea Kyung Hee University Medical Science Research Institute Kyung Hee University23 Kyungheedae-RoDongdaemun-GuSeoul02447Republic of Korea

Biodegradable hydrogels are promising biomaterials for use in controlled-release systems for skin tissue regeneration. Controlled delivery systems constitute an important aspect of tissue engineering because they can modulate various physiological responses, including early immune response, tissue remodeling, and cell proliferation and maturation in the wound-healing process. hydrogels composed of various biomaterials have been developed to overcome the limitations of conventional drug- or protein-delivery systems, such as limited targeting ability, low stability, and the induction of drug resistance. hydrogels based on keratin, a natural polymer extracted from human hair, can provide adequate cell support and control homeostasis. Consequently, they can be applied for skin tissue engineering. In this study, we prepared degradable, tunable, and biocompatible hydrogels for controllable protein delivery. We synthesized keratin-fibrinogen (KER-FBG) by the chemical coupling reaction and prepared hydrogels through polymerization with thrombin. The structures and morphologies of the KER-FBG hydrogels were confirmed. Furthermore, the mechanical properties, swelling ratio, degradation, release behavior, and biocompatibility were investigated. The KER-FBG hydrogels presented promising biological performance, indicating that the material is suitable as a controlled protein delivery carrier.

关键词： Keratin Fibrinogen hydrogel Drug delivery Degradable

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