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Chitin nanocrystal-assisted 3D bioprinting of gelatin methacrylate scaffolds

Regenerative Biomaterials 2023年第1期10卷 1192-1201页

作者： Zhengyun Ling Jian Zhao Shiyu Song Shuwei Xiao Pengchao Wang Ziyan An Zhouyang Fu Jinpeng Shao Zhuang Zhang Weijun Fu Shenghan Song School of Medicine Nankai UniversityTianjin 300071China Department of Urology The Third Medical CenterPLA General HospitalBeijing 100039China Medical School of PLA Beijing 100853China Department of Urology 960th Hospital of PLAJinan 250031China Undergraduate Student Majoring in Clinical Pharmacy Chongqing Medical UniversityChongqing 400016China Department of Urology Air Force Medical CenterBeijing 100142China Beijing Institute of Basic Medical Sciences Beijing 100850China Department of Vascular Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China

In recent years,there has been an increasing focus on the application of hydrogels in tissue *** integration of 3D bioprinting technology has expanded the potential applications of ***,few commercially available hydrogels used for 3D biological printing exhibit both excellent biocompatibility and mechanical *** methacrylate(GelMA)has good biocompatibility and is widely used in 3D ***,its low mechanical properties limit its use as a standalone bioink for 3D *** this work,we designed a biomaterial ink composed of GelMA and chitin nanocrystal(ChiNC).We explored fundamental printing properties of composite bioinks,including rheological properties,porosity,equilibrium swelling rate,mechanical properties,biocompatibility,effects on the secretion of angiogenic factors and fidelity of 3D *** results showed that adding 1%(w/v)ChiNC to 10%(w/v)GelMA improved the mechanical properties and printability of the GelMA hydrogels,promoted cell adhesion,proliferation and vascularization and enabled the printing of complex 3D *** strategy of incorporating ChiNC to enhance the performance of GelMA biomaterials could potentially be applied to other biomaterials,thereby expanding the range of materials available for ***,in combination with 3D bioprinting technology,this approach could be leveraged to bioprint scaffolds with complex structures,further broadening the potential applications in tissue engineering.

关键词： 3D bioprinting gelatin methacrylate chitin nanocrystal hydrogels scaffolds

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3D-printed gelatin methacrylate (GelMA)/ silanated silica scaffold assisted by two-stage cooling system for hard tissue regeneration

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Regenerative Biomaterials 2021年第2期8卷 50-63页

作者： Eunjeong Choi Dongyun Kim Donggu Kang Gi Hoon Yang Bongsu Jung MyungGu Yeo Min-Jeong Park SangHyun An KyoungHo Lee Jun Sik Kim Jong Chul Kim Woonhyeok Jeong Hye Hyun Yoo Hojun Jeon Research Institute of Additive Manufacturing and Regenerative Medicine Baobab Healthcare Inc55 Hanyangdaehak-RoAnsanGyeonggi-do 15588South Korea Department of Mechanical Engineering Korea Polytechnic UniversitySangidaehak-roSiheungGyeonggi-do 15073South Korea Medical Device Development Center Daegu-Gyeongbuk Medical Innovation Foundation(DGMIF)80Cheombok-roDong-guDaegu 41061South Korea Laboratory Animal Center Daegu-Gyeongbuk Medical Innovation Foundation(DGMIF)80 Cheombok-roDong-guDaegu 41061South Korea Department of Plastic and Reconstructive Surgery Dongsan Medical CenterKeimyung University College of Medicine1035 Dalgubeol-daeroDalseo-guDaegu 42601South Korea Institute of Pharmaceutical Science and Technology College of PharmacyHanyang University55 Hanyangdaehak-RoAnsanGyeonggi-Do 15588South Korea

Among many biomaterials,gelatin methacrylate(GelMA),a photocurable protein,has been widely used in 3D bioprinting process owing to its excellent cellular responses,biocompatibility and ***,GelMA still shows a low processability due to the severe temperature dependence of *** overcome this obstacle,we propose a two-stage temperature control system to effectively control the viscosity of *** optimize the process conditions,we evaluated the temperature of the cooling system(jacket and stage).Using the established system,three GelMA scaffolds were fabricated in which different concentrations(0,3 and 10 wt%)of silanated silica particles were *** evaluate the performances of the prepared scaffolds suitable for hard tissue regeneration,we analyzed the physical(viscoelasticity,surface roughness,compressive modulus and wettability)and biological(human mesenchymal stem cells growth,western blotting and osteogenic differentiation)***,the composite scaffold with greater silica contents(10 wt%)showed enhanced physical and biological performances including mechanical strength,cell initial attachment,cell proliferation and osteogenic differentiation compared with those of the *** results indicate that the GelMA/silanated silica composite scaffold can be potentially used for hard tissue regeneration.

关键词： 3D bioprinting gelatin methacrylate silanated silica cooling system human mesenchymal stem cells

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Biomimetic Ti-6Al-4V alloy/gelatin methacrylate hybrid scaffold with enhanced osteogenic and angiogenic capabilities for large bone defect restoration

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Bioactive Materials 2021年第10期6卷 3437-3448页

作者： Limin Ma Xiaolan Wang Ye Zhou Xiongfa Ji Shi Cheng Dong Bian Lei Fan Lei Zhou Chengyun Ning Yu Zhang Department of Orthopedics Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong510080China Laboratory of Basic Medicine General Hospital of Southern Theatre Command of the PLAGuangzhou510010China School of Materials Science and Engineering South China University of TechnologyGuangzhou510641China

Titanium-based scaffolds are widely used implant materials for bone defect ***,the unmatched biomechanics and poor bioactivities of conventional titanium-based implants usually lead to insufficient bone *** tackle these challenges,it is critical to develop novel titanium-based scaffolds that meet the bioadaptive requirements for load-bearing critical bone ***,inspired by the microstructure and mechanical properties of natural bone tissue,we developed a Ti-6Al-4V alloy(TC4)/gelatin methacrylate(GelMA)hybrid scaffold with dual bionic features(GMPT)for bone defect *** is composed of a hard 3D-printed porous TC4 metal scaffold(PT)backbone,which mimics the microstructure and mechanical properties of natural cancellous bone,and a soft GelMA hydrogel matrix infiltrated into the pores of PT that mimics the microenvironment of the extracellular *** to the unique dual bionic design,the resultant GMPT demonstrates better osteogenic and angiogenic capabilities than PT,as confirmed by the in vitro and rabbit radius bone defect experimental ***,controlling the concentration of GelMA(10%)in GMPT can further improve the osteogenesis and angiogenesis of *** fundamental mechanisms were revealed by RNA-Seq analysis,which showed that the concentration of GelMA significantly influenced the expression of osteogenesis-and angiogenesis-related genes via the Pi3K/Akt/mTOR *** results of this work indicate that our dual bionic implant design represents a promising strategy for the restoration of large bone defects.

关键词： 3D printing porous titanium alloys gelatin methacrylate Angiogenesis Osteogenesis

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gelatin methacrylate hydrogel scaffold carrying resveratrol-loaded solid lipid nanoparticles for enhancement of osteogenic differentiation of BMSCs and effective bone regeneration

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Regenerative Biomaterials 2021年第5期8卷 120-133页

作者： Bangguo Wei Wenrui Wang Xiangyu Liu Chenxi Xu Yanan Wang Ziqi Wang Jinnuo Xu Jianzhong Guan Pinghui Zhou Yingji Mao Department of Orthopedics First Affiliated HospitalBengbu Medical CollegeBengbu 233004China Anhui Province Key Laboratory of Tissue Transplantation Bengbu Medical CollegeBengbu 233030China School of Life Sciences Bengbu Medical CollegeBengbu 233030China Anhui Province Key Laboratory of Translational Cancer Research Bengbu Medical CollegeBengbu 233030China Department of Orthopedics Fuyang People‘s HospitalFuyang 236000China

Critical-sized bone defects caused by traumatic fractures,tumour resection and congenital malformation are unlikely to heal *** tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone *** this study,we developed an innovative bone engineering scaffold based on gelatin methacrylate(GelMA)hydrogel,obtained via a two-step procedure:first,solid lipid nanoparticles(SLNs)were loaded with resveratrol(Res),a drug that can promote osteogenic differentiation and bone formation;these particles were then encapsulated at different concentrations(0.01%,0.02%,0.04%and 0.08%)in GelMA to obtain the final Res-SLNs/GelMA *** effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and bone regeneration in rat cranial defects were evaluated using various characterization *** in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs,with the ideally slow and steady release of Res;the optimal scaffold was 0.02 Res-SLNs/***,the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility,osteoconduction and osteoinduction,thereby showing potential for application in bone tissue engineering.

关键词： gelatin methacrylate bone marrow mesenchymal stem cells solid lipid nanoparticles resveratrol bone regeneration

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Biomimetic melatonin-loaded silk fibroin/GelMA scaffold strengthens cartilage repair through retrieval of mitochondrial functions

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Journal of Materials Science & Technology 2023年第15期146卷 102-112页

作者： Mingzhuang Hou Yijian Zhang Yang Liu Xiaoyang Ge Xiayu Hu Zhijian Zhao Xin Tian Tao Liu Huilin Yang Xi Chen Fan He Xuesong Zhu Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Orthopaedic Institute Medical CollegeSoochow UniversitySuzhou 215007China Department of Pathology The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China

Articular cartilage injury induced by collision or trauma is a common sports-related condition that may progress to pain,dysfunction,and secondary osteoarthritis(OA).Limited by self-renewal potential,cartilage regeneration faces a quandary while bio-inspired novel strategies are urgently *** this study,by a soft freezing method and surface modification technique,a multi-functional silk fibroin(SF)plus gelatin methacrylate(GelMA)scaffold laden with melatonin(MT)was ***-GelMA@MT scaffold demonstrated enhanced biomechanical characteristics and long-acting melatonin *** vitro treatment with SF-GelMA@MT induced the synthesis of cartilage extracellular matrix(ECM)***,sustained release of melatonin yielded robust chondroprotective effects via improving mitochondrial polarization and antioxidant ***-GelMA@MT implantation boosted cartilage renascence in a full-thickness cartilage defect model via mitochondria-associated sirtuins 1(SIRT1)-superoxide dismutase 2(SOD2)signaling pathway in *** summary,this research proposed a welldesigned bionic composite scaffold that promotes cartilage regeneration via mitochondrial function enhancement,which is of tremendous potential for cartilage tissue engineering.

关键词： Cartilage injury Silk fibroin gelatin methacrylate Melatonin Mitochondri

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Additive-lathe 3D bioprinting of bilayered nerve conduits incorporated with supportive cells

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Bioactive Materials 2021年第1期6卷 219-229页

作者： Jingyi Liu Bin Zhang Liang Li Jun Yin Jianzhong Fu The State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical EngineeringZhejiang UniversityHangzhou310028China Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province School of Mechanical EngineeringZhejiang UniversityHangzhou310028China Department of Orthopedics No.906 Hospital of People's Liberation ArmyNingbo315040China

Nerve conduits have been identified as one of the most promising treatments for peripheral nerve injuries,yet it remains unsolved how to develop ideal nerve conduits with both appropriate biological and mechanical *** nerve conduits must make trade-offs between mechanical strength and ***,we propose a multi-nozzle additive-lathe 3D bioprinting technology to fabricate a bilayered nerve *** materials for printing consisted of gelatin methacrylate(GelMA)-based inner layer,which was cellularized with bone marrow mesenchymal stem cells(BMSCs)and GelMA/poly(ethylene glycol)diacrylate(PEGDA)-based outer *** high viability and extensive morphological spreading of BMSCs encapsulated in the inner layer was achieved by adjusting the degree of methacryloyl substitution and the concentration of *** mechanical performance of the outer layer was obtained by the addition of *** performance of the bilayered nerve conduits was assessed using in vitro culture of PC12 *** cell density of PC12 cells attached to cellularized bilayered nerve conduits was more than 4 times of that on acellular bilayered nerve *** proliferation rate of PC12 cells attached to cellularized bilayered nerve conduits was over 9 times higher than that on acellular bilayered nerve *** results demonstrate the additive-lathe 3D bioprinting of BMSCs embedded bilayered nerve conduits holds great potential in facilitating peripheral nerve repair.

关键词： Nerve conduit Mesenchymal stem cells Additive-lathe 3D bioprinting gelatin methacrylate Neuron outgrowth

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Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries

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Bioactive Materials 2021年第3期6卷 638-654页

作者： Lihua Luo Yan He Ling Jin Yanni Zhang Fernando P.Guastaldi Abdullkhaleg A.Albashari Fengting Hu Xiaoyan Wang Lei Wang Jian Xiao Lingli Li Jianming Wang Akon Higuchi Qingsong Ye School and Hospital of Stomatology Wenzhou Medical UniversityWenzhouZhejiangChina Tianyou Hospital Wuhan University of Science and TechnologyWuhan430064China Skeletal Biology Research Center Massachusetts General Hospital and Harvard School of Dental MedicineBostonMA02114USA Wenzhou Institute of Biomaterials and Engineering WenzhouZhejiang Province325000China Molecular Pharmacology Research Center School of PharmacyWenzhou Medical UniversityWenzhou325035China School of Ophthalmology and Optometry Eye HospitalWenzhou Medical UniversityWenzhouZhejiang325027China Department of Biliary and Pancreatic Surgery/Cancer Research Center Affiliated Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Center of Regenerative Medicine Renmin Hospital of Wuhan UniversityWuhan430060China

Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve *** based therapies provide a novel treatment for peripheral nerve *** this study,we first experimented an optimal scaffold material synthesis protocol,from where we selected the 10%GFD formula(10%GelMA hydrogel,recombinant human basic fibroblast growth factor and dental pulp stem cells(DPSCs))to fill a cellulose/soy protein isolate composite membrane(CSM)tube to construct a third generation of nerve regeneration conduit,*** this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat *** 12 week post implant surgery,at histologic level,we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve *** physical level,CSM-GFD achieved functional recovery assessed by a sciatic functional index *** both levels,CSM-GFD performed like what gold standard,the nerve autograft,could ***,we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in *** conclusion,we claimed that this third-generation nerve regeneration conduit,CSM-GFD,could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.

关键词： Dental pulp stem cells Human basic fibroblast growth factor gelatin methacrylate Large gap Peripheral nerve injuries Nerve graft

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