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Chinese Journal of Polymer Science 2021年第8期39卷 957-965页

作者： Xue-Bin Ma Rong Yang Kanaparedu P.C.Sekhar Bo Chi Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education School of Chemistry and Chemical Engineering Shandong University State Key Laboratory of Materials-Oriented Chemical Engineering College of Food Science and Light Industry Nanjing Tech University

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(γ-glutamic acid)(HA/γ-PGA) hydrogels exhibit step-bystep tunable swelling behavior, enzymatic degradation behavior and mechanical properties. Mechanical performance tests show that the storage moduli of HA/γ-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 3 T3 cells encapsulated in HA/γ-PGA hydrogel exhibit a high cell viability, indicating a good cytocompatibility of HA/γ-PGA ***, the developed HA/γ-PGA hydrogel as an injectable biomaterial has a good potential in soft tissue engineering.

关键词： Hyaluronic acid Poly( γ -glutamic acid) injectable hydrogel Tissue engineering

An injectable alginate/fibrin hydrogel encapsulated with cardiomyocytes and VEGF for myocardial infarction treatment

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Journal of Materials Science & Technology 2023年第12期143卷 198-206页

作者： Chunxia Liu Yong Wu Hong Yang Kunyan Lu Haixin Zhang Yuanyuan Wang Jingjing Wang Linan Ruan Zhenya Shen Qian Yu Yanxia Zhang Institute for Cardiovascular Science and Department of Cardiovascular Surgery of the First Affiliated Hospital Suzhou Medical College of Soochow UniversitySoochow UniversitySuzhou 215000China State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China Key Laboratory of Polymeric Materials Design and Synthesis for Biomedical Function Soochow UniversitySuzhou 215123China

Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death *** to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation of exogenous CMs becomes a promising option for MI ***,the low retention and survival of transplanted cells still limit the clinical translation of cell ***,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 *** 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 ***,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 *** 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.

关键词： injectable hydrogel Alginate Fibrin Cardiomyocytes VEGF Myocardial infarction

Synergistic osteogenic and angiogenic effects of KP and QK peptides incorporated with an injectable and self-healing hydrogel for efficient bone regeneration

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Bioactive Materials 2022年第12期7卷 267-283页

作者： Runze Li Chen Zhou Jun Chen Haotian Luo Ruoyu Li Danying Chen Xuenong Zou Weicai Wang Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen University56 Lingyuanxi RoadGuangzhou510055China Department of Organ Transplantation Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China The Key Laboratory of Imflammation and Autoimmune Diseases Guangzhou510280China Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology Department of Spine SurgeryThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou510080China

Irregular defects generated by trauma or surgery in orthopaedics practice were usually difficult to be fitted by the preformed traditional bone graft substitute. Therefore, the injectable hydrogels have attracted an increasing interest for bone repair because of their fittability and mini-invasivity. However, the uncontrollable spreading or mechanical failures during its manipulation remain a problem to be solved. Moreover, in order to achieve vascularized bone regeneration, alternatives of osteogenic and angiogenic growth factors should be adopted to avoid the problem of immunogenicity and high cost. In this study, a novel injectable self-healing hydrogel system (GMO hydrogel) loaded with KP and QK peptides had been developed for enhancing vascularized regeneration of small irregular bone defect. The dynamic imine bonds between gelatin methacryloyl and oxidized dextran provided the GMO hydrogel with self-healing and shear-thinning abilities, which led to an excellent injectability and fittability. By photopolymerization of the enclosed GelMA, GMO hydrogel was further strengthened and thus more suitable for bone regeneration. Besides, the osteogenic peptide KP and angiogenic peptide QK were tethered to GMO hydrogel by Schiff base reaction, leading to desired releasing profiles. In vitro, this composite hydrogel could significantly improve the osteogenic differentiation of BMSCs and angiogenesis ability of HUVECs. In vivo, KP and QK in the GMO hydrogel demonstrated a significant synergistic effect in promoting new bone formation in rat calvaria. Overall, the KP and QK loaded GMO hydrogel was injectable and self-healing, which can be served as an efficient approach for vascularized bone regeneration via a minimally invasive approach.

关键词： injectable hydrogel Self-healing KP peptide QK peptide Bone tissue engineering

injectable self-healing hydrogel with siRNA delivery property for sustained STING silencing and enhanced therapy of intervertebral disc degeneration

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Bioactive Materials 2022年第3期7卷 29-43页

作者： Jiaxin Chen Haifeng Zhu Yutao Zhu Chenchen Zhao Shengyu Wang Yixin Zheng Ziang Xie Yang Jin Honghai Song Linjun Yang Jin Zhang Jiayong Dai Zhijun Hu Huaiyu Wang Department of Orthopaedic Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineKey Laboratory of Musculoskeletal System DegenerationRegeneration Translational Research of Zhejiang ProvinceEast Qing Chun RoadHangzhou310016PR China College of Chemical Engineering Fuzhou University2 Xueyuan RoadFuzhou350108PR China Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055GuangdongPR China

Inflammatory responses of nucleus pulposus(NP)can induce imbalanced anabolism and catabolism of extracellular matrix,and the cytosolic dsDNA accumulation and STING-NF-κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc(IVD)***,we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid(HA-CHO)and poly(amidoamine)PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment,where the formation of dynamic Schiff base bonds in the system(siSTING@HPgel)was able to overcome the shortcomings such as low cellular uptake,short half-life,and rapid degradation of siRNA-based *** not only formed complexes with siRNA to promote siRNA transfection,but also served as dynamic crosslinker to construct hydrogel,and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP ***,the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model,revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.

关键词： STING IVD degeneration siRNA delivery injectable hydrogel Dynamic Schiff base

Release of VEGF and BMP9 from injectable alginate based composite hydrogel for treatment of myocardial infarction

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Bioactive Materials 2021年第2期6卷 520-528页

作者： Yong Wu Tianqi Chang Weiqian Chen Xiaoyu Wang Jingjing Li Yueqiu Chen You Yu Zhenya Shen Qian Yu Yanxia Zhang Institute for Cardiovascular Science&Department of Cardiovascular Surgery of the First Affiliated Hospital Medical CollegeSoochow UniversitySuzhou215000PR China State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou215123PR China

Myocardial infarction(MI)is one of cardiovascular diseases that pose a serious threat to human *** pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery,necrosis of myocardial cells,inflammation,and myocardial *** at the treatment of different stages of MI,in this work,an injectable alginate based composite hydrogel is developed to load vascular endothelial active factor(VEGF)and silk fibroin(SF)microspheres containing bone morphogenetic protein 9(BMP9)for releasing VEGF and BMP9 to realize their respective *** results of in vitro experiments indicate a rapid initial release of VEGF during the first few days and a relatively slow and sustained release of BMP9 for days,facilitating the formation of blood vessels in the early stage and inhibiting myocardial fibrosis in the long-term stage,*** injection of such composite hydrogel into the infarct border zone of mice MI model via multiple points promotes angiogenesis and reduces the infarction *** together,these results indicate that the dual-release of VEGF and BMP9 from the composite hydrogel results in a collaborative effect on the treatment of MI and improvement of heart function,showing a promising potential for cardiac clinical application.

关键词： Myocardial infarction injectable hydrogel Silk fibroin microspheres Angiogenesis Myocardial fibrosis

Easily-injectable shear-thinning hydrogel provides long-lasting submucosal barrier for gastrointestinal endoscopic surgery

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Bioactive Materials 2022年第9期7卷 44-52页

作者： Yinxiang Tang Minhui Hu Fuxin Tang Rongkang Huang Hui Wang Dingcai Wu Ping Lan Materials Science Institute Key Laboratory for Polymeric Composite and Functional Materials of Ministry of EducationSchool of ChemistrySun Yat-sen UniversityGuangzhou510275China Department of Gastrointestinal Endoscopy Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesThe Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhou510655China Department of Colorectal Surgery Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesThe Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhou510655China Institute of Biomedical Innovation and Laboratory of Regenerative Medicine and Biomaterials Biomedical Material Conversion and Evaluation Engineering Technology Research Center of Guangdong ProvinceGuangzhou510655China

Submucosal injection material has shown protective effect against gastrointestinal injury during endoscopic surgery in ***,the protective ability of existing submucosal injection material is strictly limited by their difficult injectability and short barrier ***,we report a shear-thinning gellan gum hydrogel that simultaneously has easy injectability and long-lasting barrier function,together with good hemostatic property and ***-thinning property endows our gellan gum hydrogel with excellent endoscopic injection performance,and the injection pressure of our gellan gum hydrogel is much lower than that of the small molecule solution(50 wt%dextrose)when injected through the endoscopic *** importantly,our gellan gum hydrogel shows much stronger barrier retention ability than normal saline and sodium hyaluronate solution in the ex vivo and in vivo ***,our epinephrine-containing gellan gum hydrogel has a satisfactory hemostatic effect in the mucosal lesion resection model of *** results indicate an appealing application prospect for gellan gum hydrogel utilizing as a submucosal injection material in endoscopic surgery.

关键词： Shear-thinning injectable hydrogel Gellan gum Long-lasting barrier Endoscopic surgery

Reducing relapse and accelerating osteogenesis in rapid maxillary expansion using an injectable mesoporous bioactive glass/fibrin glue composite hydrogel

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Bioactive Materials 2022年第12期7卷 507-525页

作者： Hanjiang Zhao Xiangyu Wang Anting Jin Minjiao Wang Zeying Wang Xingtai Huang Jiewen Dai Xudong Wang Dan Lin Steve GF.Shen Department of Oral&Cranio-Maxillofacial Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghai200011PR China Shanghai University of Medicine and Health Sciences Shanghai201318China

Rapid maxillary expansion(RME),as a common treatment for craniomaxillofacial deformity,faces the challenge of high relapse rates and unsatisfactory therapeutic *** this study,a standardized Sprague-Dawley(SD)rat RME model was first established with a modified expander as well as retainer design and optimized anterior maxillary expanding force of 100 g which exerted the most synchronized mobility of mid-palatal suture and *** the standardized model,the high relapse rate was proven to be attributed to insufficient osteogenesis in expanded suture,requiring long-term retainer wearing in clinical *** reduce the relapse rate,mesoporous bioactive glass/fibrin glue(MBG/FG)composite hydrogels were developed for an in situ minimal invasive injection that enhance osteogenesis in the expanded *** component of 1 wt%MBG was adopted for enhanced mechanical strength,matched degradation rate and ion dissolution,excellent in vitro biocompatibility and *** of 1%MBG/FG composite hydrogel on osteogenesis in expanded mid-palatal sutures with/without retention were evaluated in the standardized *** results demonstrated that injection of 1%MBG/FG composite hydrogel significantly promoted bone formation within the expanded mid-palatal suture,inhibited osteoclastogenesis and benefited the balance of bone remodeling towards *** of retainer and injectable biomaterial was demonstrated as a promising treatment to reduce relapse rate and enhance osteogenesis after *** model establishment and the composite hydrogel development in this article might provide new insight to other craniomaxillofacial deformity treatment and design of bone-repairing biomaterials with higher regenerative efficiency.

关键词： Rapid maxillary expansion Sutural distraction osteogenesis injectable hydrogel Mesoporous bioactive glass Bone regeneration

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可注射水凝胶再生修复退变髓核的研究进展

临床医学进展 2024年第9期14卷 421-427页

作者：李名广黄卫三峡大学附属仁和医院骨科，湖北宜昌

目的：可注射水凝胶再生修复退变髓核的研究进展进行综述。方法：广泛查阅近年来国内外相关研究文献，对不同类型可注射水凝胶用于髓核再生修复研究进展进行总结。结果：可注射水凝胶在机械性能、组织相容性、微创置入及负载生物活性物... 详细信息

目的：可注射水凝胶再生修复退变髓核的研究进展进行综述。方法：广泛查阅近年来国内外相关研究文献，对不同类型可注射水凝胶用于髓核再生修复研究进展进行总结。结果：可注射水凝胶在机械性能、组织相容性、微创置入及负载生物活性物质等方面具有优势，目前关于可注射水凝胶在髓核再生修复的临床研究也取得了较好的结果，但其临床转化还需解决机械强度匹配、水凝胶泄露移位的问题。结论：可注射水凝胶的特性可以实现水凝胶的微创化置入，在成分和结构上模拟原生髓核组织，恢复髓核微环境和生物力学功能，同时可以作为生物活性物质的载体促进髓核再生，在髓核修复领域具有广阔的应用场景。

关键词：髓核组织再生可注射水凝胶 Nucleus Pulposus Tissue Regeneration injectable hydrogel

injectable Hyaluronic Acid/Poly(y-glutamic acid)hydrogel with Step-by-step Tunable Properties for Soft Tissue Engineering

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Chinese Journal of Polymer Science 2021年第8期39卷 957-965,I0005页

作者： Xue-Bin Ma Rong Yang Kanaparedu P.C.Sekhar Bo Chi Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education School of Chemistry and Chemical EngineeringShandong UniversityJinan 250100China State Key Laboratory of Materials-Oriented Chemical Engineering College of Food Science and Light IndustryNanjing Tech UniversityNanjing 211816China

injectable hydrogels as an important class of biomaterials have gained much attention in tissue ***,their crosslinking degree is difficult to be controlled after being injected into *** we all know,the crosslinking degree strongly influences the physicochemical properties of ***,developing an injectable hydrogel with tunable crosslinking degree in vivo is important for tissue ***,we present a dual crosslinking strategy to prepare injectable hydrogels with step-by-step tunable crosslinking degree using Schiff base reaction and *** developed hyaluronic acid/poly(y-glutamic acid)(HA/y-PGA)hydrogels exhibit step-by-step tunable swelling behavior,enzymatic degradation behavior and 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 *** addition,NIH 3T3 cells encapsulated in HA/y-PGA hydrogel exhibit a high cell viability,indicating a good cytocompatibility of HA/y-PGA ***,the developed HA/y-PGA hydrogel as an injectable biomaterial has a good potential in soft tissue engineering.

关键词： Hyaluronic acid Poly(y-glutamic acid) injectable hydrogel Tissue engineering

injectable hydrogels for spinal cord injury repair

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Engineered Regeneration 2022年第4期3卷 407-419页

作者： Huan Wang Hui Zhang Zhongyu Xie Keng Chen Mengjun Ma Yuejiao Huang Minli Li Zhaopeng Cai Peng Wang Huiyong Shen The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhen 518033China School of Life Science and Technology Southeast UniversityNanjing 210096China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China

Spinal cord injury(SCI)often causes severe functional impairment of body,which leads to a huge burden to the patient and the whole *** strategies,especially biomaterials,have been employed for SCI *** various biomaterials,injectable hydrogels have attracted much attention because of their ability to load functional components and be injected into the lesioned area without *** this review,we summarize the recent progress in injectable hydrogels for SCI *** firstly introduce the pathophysiology of SCI,which reveals the mechanism of clinical manifestations and determines the therapeutic ***,we describe the original sources of polymers and the crosslinking manners in forming *** that,we focus on the in vivo therapeutic strategies and effects of injectable ***,the recent challenges and future outlook of injectable hydrogel for SCI repair are concluded and *** believe this review can be helpful and inspire the further development of injectable hydrogels for SCI repair.

关键词： injectable hydrogel Spinal cord injury Extracellular matrix Neuroprotection Nerve regeneration