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Development of a multicellular 3D-bioprinted microtissue model of human periodontal ligament-alveolar bone biointerface:Towards a pre-clinical model of periodontal diseases and personalized periodontal tissue engineering

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Genes & Diseases 2022年第4期9卷 1008-1023页

作者： Murat Taner Vurat ŞükranŞeker Özge Lalegül-Ülker Mahmut Parmaksiz Ayşe Eser Elçin Yaşar Murat Elçin Tissue Engineering Biomaterials and Nanobiotechnology LaboratoryAnkara University Faculty of ScienceAnkara University Stem Cell InstituteAnkara 06100Turkey Biovalda Health Technologies Inc.Ankara 06100Turkey

While periodontal (PD) disease is among princ.pal causes of tooth loss worldwide, regulation of concomitant soft and mineralized PD tissues, and PD pathogenesis have not been completely clarified yet. Besides, relevant pre-clinical models and in vitro platforms have limitations in simulating human physiology. Here, we have harnessed three-dimensional bioprinting (3DBP) technology for developing a multi-cellular microtissue model resembling PD ligament-alveolar bone (PDL-AB) biointerface for the first time. 3DBP parameters were optimized;the physical, chemical, rheological, mechanical, and thermal properties of the constructs were assessed. Constructs containing gelatin methacryloyl (Gel-MA) and hydroxyapatite-magnetic iron oxide nanoparticles showed higher level of compressive strength when compared with that of Gel-MA constructs. Bioprinted self-supporting microtissue was cultured under flow in a microfluidic platform for >10 days without significant loss of shape fidelity. Confocal microscopy analysis indicated that encapsulated cells were homogenously distributed inside the matrix and preserved their viability for >7 days under microfluidic conditions. Immunofluorescence analysis showed the cohesion of stromal cell surface marker-1+ human PDL fibroblasts containing PDL layer with the osteocalcin+ human osteoblasts containing mineralized layer in time, demonstrating some permeability of the printed constructs to cell migration. Preliminary tetracycline interaction study indicated the uptake of model drug by the cells inside the 3D-microtissue. Also, the non-toxic levels of tetracycline were determined for the encapsulated cells. Thus, the effects of tetracyclines on PDL-AB have clinical significance for treating PD diseases. This 3D-bioprinted multi-cellular periodontal/osteoblastic microtissue model has potential as an in vitro platform for studying processes of the human PDL.

关键词： 3D bioprinting Alveolar bone Microtissue model Organ-on-a-chip .Periodontal ligament Periodontal tissue engineering Periodontal-osteoblastic biointer face Periodontium-on-a-chip

A multicenter, prospective, randomized clinical study to evaluate the efficacy and safety of fibrin sealant as an adjunct to sutured dural repair

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Chinese Medical Journal 2022年第20期135卷 2506-2508页

作者： Rutong Yu Wei Zhu Richard Kocharian Bogdan Ilie Zhong Wang Dezhi Kang Gang Zhao Hua Yang Kai Shu Xianzhi Liu Yiquan Ke Shun Qu Ying Mao Department of Neurosurgery The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu 221006China Department of Neurosurgery Huashan HospitalFudan UniversityShanghai 200040China Ethicon Inc.A Johnson&Johnson CompanyRaritanNJ 08869USA Department of Neurosurgery The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215006China Department of Neurosurgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China Department of Neurosurgery The First Hospital of Jilin UniversityChangchunJilin 130499China Department of Neurosurgery The Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou 550004China Department of Neurosurgery Tongji HospitalTongji Medical College of HUSTWuhanHubei 430014China Department of Neurosurgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Neurosurgery Zhujiang Hospital of Southern Medical UniversityGuangzhouGuangdong 510260China Ethicon Johnson&Johnson Medical(Shanghai)Co.Ltd.Shanghai 200233China

To the Editor:Cerebrospinal fluid(CSF)leakage inc.eases the risk of post-operative complications following cranial surgery,and its progression is not always ***,surgeons use various methods to achieve watertight closure of CSF,inc.uding synthetic sealants,collagen or gelatin based sponges,[1]and fibrin sealants(FS).[2,3]Bioseal(Porcine Fibrin Sealant Kit,Guangzhou Bioseal Biotech Co.,Ltd.,Guangzhou,China)is a virus-inactivated porcine plasma-derived FS that has been approved as a supportive treatment to control surgical bleeding.

关键词： fibrin suture sponge

Enhancing cartilage repair with optimized supramolecular hydrogel-based scaffold and pulsed electromagnetic field

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Bioactive Materials 2023年第4期22卷 312-324页

作者： Yucong Li Linlong Li Ye Li Lu Feng Bin Wang Ming Wang Haixing Wang Meiling Zhu Yongkang Yang Erik IWaldorff Nianli Zhang Ingmar Viohl Sien Lin Liming Bian Wayne Yuk-Wai Lee Gang Li Department of Orthopaedics&Traumatology Stem Cells and Regenerative Medicine LaboratoryLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong Special Administrative Region Research&Clinical Affairs Orthofix Medical Inc.LewisvilleTXUSA Department of Rehabilitation Sciences Hong Kong Polytechnic UniversityHong Kong Special Administrative Region Innovation Centre for Advanced Interdisciplinary Medicine Key Laboratory of Biological Targeting DiagnosisTherapy and Rehabilitation of Guangdong Higher Education InstitutesThe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhenPR China School of Biomedical Sciences and Engineering National Engineering Research Center for Tissue Restoration and ReconstructionKey Laboratory of Biomedical Materials and Engineering of the Ministry of EducationSouth China University of TechnologyGuangzhouPR China Department of Orthopaedics and Traumatology SH Ho Scoliosis Research LaboratoryJoint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing UniversityThe Chinese University of Hong KongHong Kong Special Administrative Region

Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged *** is widely used because it could provide rapid defect filling and proper structure support,and is biocompatible for cell aggregation and matrix *** have been made to seek suitable scaffolds for cartilage tissue *** Alg-DA/Ac-β-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing *** time,swelling ratio,biodegradability and biocompatibility of the hydrogels were systematically characterized,and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage ***,the new hydrogel design introduces a pre-gel state before photo-crosslinking,where inc.eased viscosity and decreased fluidity allow the gel to remain in a semi-solid *** granted multiple administration routes to the hydrogels,which brings hydrogels the ability to adapt to complex clinical *** electromagnetic fields(PEMF)have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic *** treatment offers a better clinical outcome with fewer,if any,side effects,and wildly used in musculoskeletal tissue *** we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue *** this study,the as-prepared Alg-DA/Ac-β-CD/gelatin hydrogels were utilized in the rat osteochondral defect model,and the potential application of PEMF in cartilage tissue engineering were *** treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro,and facilitate chondrogenesis and cartilage repair in *** of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment,this newly proposed tissue engineering strategy r

关键词： Supramolecular hydrogels Pulsed electromagnetic field Cartilage tissue engineering Mesenchymal stem cells Chondrogenesis

Transporting Mammalian Cells at Ambient Temperature:A Viable Alternative to Dry Ice

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Advances in Bioscience and Biotechnology 2017年第4期8卷 127-133页

作者： Steingrimur Stefansson Seunghyun Han Ye In Jeon David S.Chung Peter Hwang Huyen Le John L.Warden David Ho HeMemics Biotechnologies inc RockvilleUSA Johns Hopkins University BaltimoreUSA George Washington University WashingtonDCUSA Division of Biology and Medicine Brown UniversityProvidenceUSA Thomas Jefferson High School for Science and Technology AlexandriaUSA Nauah Solutions McleanUSA

The most common method of shipping cells between institutes and companies is sending them frozen, usually treated with anti-freeze solution (most commonly DMSO because it is less toxic than many alternatives), and then packaging them in dry ice for shipment. However many countries place restrictions on dry ice shipments. An alternative to shipping frozen cell vials is to send flasks of growing cells in media. This also has problems because cells in media have limited viability and the flasks can leak. Here we report on an alternative method for shipping viable cells at ambient temperature without dry ice or in media filled flasks. In this study we report on the development and properties of HemSol?. This is an inexpensive, eco-friendly and protects cell integrity at ambient temperature while maintaining viability. We have previously shown that HemSol? protects platelet and RBC function in cold storage and circulating tumor cells up to 6 days. Therefore we wanted to know if HemSol? could also be used to transport live cells. Sinc. HemSol? is a liquid, we experimented with encasing the cells with HemSol? and gelatin so as to prevent dry ice shipment of cells and circumvent the shipping of cells in media. We performed mock shipping experiments where cells were stored in HemSol? gel kept at room temperature on a lab benchtop and cells stored in dry ice was also kept on lab benchtop for up to 2 days. After the mock shipping period, we analyzed cells for their functions. Our results show that cells in HemSol? gel have greater than 95% viability and restored biological functions in 2 hours, whereas, cells shipped in dry ice required more than 24 hours to recover and needed media change to remove the DMSO.

关键词： HemSol^(TM) HemSol^(TM) Gel Transportation Short Term Storage Cells Shipment Dry Ice Ambient Temperature Shipment

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 inc.uding 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