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Anti-inflammatory and anabolic biphasic scaffold facilitates osteochondral tissue regeneration in osteoarthritic joints

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Journal of Materials Science & Technology 2023年第25期156卷 20-31页

作者： Xiangbo Meng Ling Li Cuishan Huang Keda Shi Qingqiang Zeng Chunyi Wen Sibylle Grad mauro alini Ling Qin Xinluan Wang Translational Medicine R&D Center Institute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China AO Research Institute Davos Clavadelerstrasse 8Davos Platz 7270Switzerland Musculoskeletal Research Laboratory Department of Orthopaedics & TraumatologyThe Chinese University of Hong KongHong Kong SAR 999077China CAS-HK Joint Lab of Biomaterials Joint Laboratory of Chinese Academic of Science and Hong Kong for BiomaterialsTranslational Medicine Research and Development CenterShenzhen Institutes of Advanced Technology of Chinese Academy of Sciences and The Chinese University of Hong KongChina Department of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic UniversityHong Kong SAR 999077China

Osteochondral defects (OCD) are common but difficult to heal due to the low intrinsic repair capacity of cartilage and its complex hierarchical structure. In osteoarthritis (OA), OCD become more challenging to repair as both cartilage and subchondral bone regeneration are further impaired due to the arthritic environment. Numerous biomaterials have been developed and tested in osteochondral defects while ignoring the inflammatory environment. To target this challenging underlying pathophysiology, we designed and fabricated a biphasic porous and degradable scaffold incorporating anti-inflammatory and anabolic molecules by low-temperature rapid prototyping technology, and its effects on promoting osteochondral regeneration were evaluated using our well-established OA-OCD rabbit model. The biphasic porous scaffolds consisted of poly lactic-co-glycolic acid (PLGA) with kartogenin (KGN) for cartilage repair and PLGA and β-calcium phosphate (PLGA/β-TCP) with cinnamaldehyde (CIN) for subchondral bone repair. KGN is a molecule for promoting chondrogenesis and CIN is a phytomolecule for enhancing osteogenesis and alleviating inflammation. The biphasic scaffolds PLGA/KGN-PLGA/β-TCP/CIN (PK/PTC) with bio-mimic structure provided stable mechanical properties and exhibited excellent biocompatibility to support cell adhesion, proliferation, migration, and distribution. Furthermore, KGN and CIN within biphasic scaffolds could be released in a controlled and sustained mode, and the biphasic scaffold degraded slowly in vitro . Evaluating the repair of 16-weeks post-implantation into critically sized OA-OCD rabbit models revealed that the biphasic scaffold could promote subchondral bone and cartilage regeneration, as well as reverse subchondral osteosclerosis caused by inflammation in vivo . These findings support the utilization of the PK/PTC scaffold for osteochondral regeneration and provide a promising potential strategy for clinical application for the treatment of patients with

关键词： Biphasic scaffold Osteochondral defect Osteoarthritis Kartogenin Cinnamaldehyde Anti-inflammation

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Decellularized extracellular matrix particle-based biomaterials for cartilage repair applications

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Journal of Materials Science & Technology 2023年第29期160卷 194-203页

作者： Peng Guo Nan Jiang Carina Mini Gregor Miklosic Songsong Zhu Andrea J.Vernengo Matteo D’Este Sibylle Grad mauro alini Zhen Li AO Research Institute Davos Davos 7270Switzerland Department of Spine Surgery The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Disease and West China Hospital of Stomatology Sichuan UniversityChengdu 610041China Institute for Biomechanics ETH ZürichZürich 8093Switzerland

Cartilage Decellularized ExtraCellular Matrix(dECM)materials have shown promising cartilage regenera-tion capacity due to their chondrogenic ***,the limited retention of ECM components and the reduced integrity of functional ECM molecules during traditional decellularization processes im-pair the biomimicry of these *** current study aims to fabricate biomimetic materials con-taining decellularized cartilage particles that have an intact molecular structure and native composition as biomaterial inks and hydrogels for cartilage *** this,we established a novel two-fraction de-cellularization strategy for the preparation of reconstituted dECM(rdECM)particles by mixing the two-fraction components,as well as a one-fraction decellularization strategy for the preparation of biomimetic dECM(bdECM)*** acid-tyramine(THA)hydrogels containing rdECM or bdECM particles were produced and characterized via rheological test,swelling and stability evaluation,and compression *** results showed that our novel decellularization strategies preserved intact proteoglycans and collagen at a higher retention rate with adequate DNA removal compared to traditional methods of *** addition of rdECM or bdECM particles significantly increased the shear moduli of the THA bioinks while preserving their shear-thinning *** particle-embedded THA hydrogels also achieved long-term stability with a swelling ratio of 70%and high retention of glycosaminoglycans and collagen after long-term incubation,while rdECM particle-embedded THA hydrogels showed unsat-isfactory stability as self-standing *** to pure THA hydrogels,the addition of bdECM particles significantly enhanced the compression *** summary,our decellularization methods are successful in the retention of functional and intact cartilage components with high *** rdECM and bdECM particles can be supplemented in THA bioinks for biomimet

关键词： Cartilage tissue engineering Decellularized extracellular matrix Proteoglycan integrity Biomimetic hydrogels Biomaterial Bioink

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Visible Light-Induced 3D Bioprinting Technologies and Corresponding Bioink Materials for Tissue Engineering: A Review

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Engineering 2021年第7期7卷 966-978页

作者： Zizhuo Zheng David Eglin mauro alini Geoff RRichards Ling Qin Yuxiao Lai Centre for Translational Medicine Research and Development Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Key Laboratory of Health Informatics Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China AO Research Institute Davos CH-7270Switzerland Musculoskeletal Research Laboratory Department of Orthopedics and TraumatologyThe Chinese University of Hong KongHong Kong 999077China Guangdong Engineering Laboratory of Biomaterials Additive Manufacturing Shenzhen 518055China

Three-dimensional(3D)bioprinting based on traditional 3D printing is an emerging technology that is used to precisely assemble biocompatible materials and cells or bioactive factors into advanced tissue engineering *** technology,particularly photo-cured bioprinting strategies,plays an important role in the field of tissue engineering *** successful implementation of 3D bioprinting is based on the properties of photopolymerized *** hydrogel is an attractive biomaterial that is polymerized rapidly and enables process control in space and *** is frequently initiated by ultraviolet(UV)or visible ***,UV light may cause cell damage and thereby,affect cell ***,visible light is considered to be more biocompatible than UV light for *** this review,we provide an overview of photo curing-based bioprinting technologies,and describe a visible light crosslinkable bioink,including its crosslinking mechanisms,types of visible light initiator,and biomedical *** also discuss existing challenges and prospects of visible light-induced 3D bioprinting devices and hydrogels in biomedical areas.

关键词： Medical additive manufacturing Bioink Tissue engineering 3D bioprinting

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A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration

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Bioactive Materials 2022年第3期7卷 281-298页

作者： Peng Guo Xizhe Liu Penghui Zhang Zhongyuan He Zhen Li mauro alini RGeoff Richards Sibylle Grad Martin J.Stoddart Guangqian Zhou Xuenong Zou Danny Chan Wei Tian Dafu Chen Manman Gao Zhiyu Zhou Shaoyu Liu Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury Department of Orthopaedic SurgeryThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenChina Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina AO Research Institute Davos DavosSwitzerland Shenzhen Key Laboratory of Anti-aging and Regenerative Medicine Department of Medical Cell Biology and GeneticsHealth Sciences CenterShenzhen UniversityShenzhenChina School of Biomedical Sciences LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina Laboratory of Bone Tissue Engineering Beijing Laboratory of Biomedical MaterialsBeijing Research Institute of Orthopaedics and TraumatologyBeijing JiShuiTan HospitalBeijingChina Department of Sport Medicine Inst Translat MedThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People’s HospitalShenzhenChina

The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined,which significantly limits the application of such bioactive ***,the transcriptional landscapes of different osteogenic microenvironments,including three-dimensional(3D)hydroxyapatite(HA)scaffolds and osteogenic medium(OM),for mesenchymal stromal cells(MSCs)in vitro were mapped at single-cell *** findings suggested that an osteogenic process reminiscent of endochondral ossification occurred in HA scaffolds through sequential activation of osteogenic-related signaling pathways,along with inflammation and angiogenesis,but inhibition of adipogenesis and ***,we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling *** of MSCs was also *** vitro ossification of LRRC75A+MSCs was shown to have better utilization of WNT-related ossification process,and PCDH10+MSCs with superiority in hydroxyapatite-related osteogenic *** findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds,providing new insights for the improvement of osteogenic *** atlas provides a blueprint for research on MSC heterogeneity and the osteogenic microenvironment of HA scaffolds and a database reference for the application of bioactive materials for bone regeneration.

关键词： inflammation bioactive finding

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Quality control methods in musculoskeletal tissue engineering:from imaging to biosensors

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Bone Research 2021年第4期9卷 473-493页

作者： Daniele Zuncheddu Elena Della Bella Andrea Schwab Dalila Petta Gaia Rocchitta Silvia Generelli Felix Kurth Annapaola Parrilli Sophie Verrier Julietta V.Rau Marco Fosca Margherita Maioli Pier Andrea Serra mauro alini Heinz Redl Sibylle Grad Valentina Basoli AC Research Institute Davos Clavadelerstrasse 87270 DavosSwitzerland Regenerative Medicine Technologies Lab Ente Ospedaliero Cantonale(EOC)Via Tesserete 466900 LuganoSwitzerland Department of Medical Surgical and Experimental SciencesUniversity of SassariViale San Pietro 43/b07100 SassariItaly Centre Suisse d'Electronique et de Microtechnique Bahnhofstrasse 17302 LandquartSwitzerland Center for X-ray Analytics Empa-Swiss Federal Laboratories for Materials Science and TechnologyUberlandstrasse 1298600 DubendorfSwitzerland lstituto di Struttura della Materia Consiglio Nazionale delle Ricerche(ISM-CNR)Via del Fosso del Cavaliere100-00133 RomeItaly Sechenov First Moscow State Medical University Trubetskaya 8build.2119991 MoscowRussian Federation Department of Biomedical Sciences University of SassariViale San Pietro 43/b07100 SassariItaly Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in AUVA trauma research center DonaueschingenstraBe 131200 ViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria

Tissue engineering is rapidly progressing toward clinical *** the musculoskeletal field,there has been an increasing necessity for bone and cartilage *** the promising translational potential of tissue engineering approaches,careful attention should be given to the quality of developed constructs to increase the real applicability to *** a general introduction to musculoskeletal tissue engineering,this narrative review aims to offer an overview of methods,starting from classical techniques,such as gene expression analysis and histology,to less common methods,such as Raman spectroscopy,microcomputed tomography,and biosensors,that can be employed to assess the quality of constructs in terms of viability,morphology,or matrix deposition.A particular emphasis is given to standards and good practices(GXP),which can be applicable in different ***,a classification of the methods into destructive,noninvasive,or conservative based on the possible further development of a preimplant quality monitoring system is *** in musculoskeletal tissue engineering have not yet been used but have been proposed as a novel technology that can be exploited with numerous advantages,including minimal invasiveness,making them suitable for the development of preimplant quality control systems.

关键词： skeletal starting spite

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Ageing affects chondroitin sulfates and their synthetic enzymes in the intervertebral disc

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Signal Transduction and Targeted Therapy 2017年第1期2卷 100-107页

作者： Estelle C Collin Oliver Carroll Michelle Kilcoyne Marianna Peroglio Eugene See Doris Hendig mauro alini Sibylle Grad Abhay Pandit Centre for Research in Medical Devices(CÚRAM) National University of IrelandGalwayIreland Department of Microbiology School of Natural SciencesNational University of IrelandGalwayIreland Glycoscience Group National University of IrelandGalwayIreland AO Research Institute DavosSwitzerland Institut fur Laboratoriums-und Transfusionsmedizin Herz-und Diabeteszentrum Nordrhein-WestfalenUniversitatsklinik der Ruhr-Universitat BochumBad OeynhausenGermany

The depletion of chondroitin sulfates(CSs)within the intervertebral disc(IVD)during degenerative disc disease(DDD)results in a decrease in tissue hydration,a loss of fluid movement,cell apoptosis,a loss of nerve growth inhibition and ultimately,the loss of disc *** date,little is known with regards to the structure and content of chondroitin sulfates(CSs)during IVD *** behavior of glycosaminoglycans(GAGs),specifically CSs,as well as xylosyltransferase I(XT-I)and glucuronyltransferase I(GT-I),two key enzymes involved in CS synthesis as a primer of glycosaminoglycan(GAG)chain elongation and GAG synthesis in the nucleus pulposus(NP),respectively,were evaluated in a bovine ageing IVD ***,we showed significant changes in the composition of GAGs during the disc ageing process(6-month-old,2-year-old and 8-year-old IVDs representing the immature to mature skeleton).The CS quantity and composition of annulus fibrosus(AF)and NP were *** expression of both XT-I and GT-I was detected using immunohistochemistry.A significant decrease in GAGs was observed during the ageing *** are affected at both the structural and quantitative levels with important changes in sulfation observed upon maturity,which correlated with a decrease in the expression of both XT-I and GT-I.A progressive switch of the sulfation profile was noted in both NP and AF tissues from 6 months to 8 *** changes give an appreciation of the potential impact of CSs on the disc biology and the development of therapeutic approaches for disc regeneration and repair.

关键词： ageing representing synthetic

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可见光引发的3D生物打印技术及其生物墨水材料在组织工程领域的研究进展

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Engineering 2021年第7期7卷 169-196页

作者：郑子卓 David Eglin mauro alini Geoff R.Richards 秦岭赖毓霄 Centre for Translational Medicine Research and Development Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Key Laboratory of Health Informatics Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences AO Research Institute Musculoskeletal Research Laboratory Department of Orthopedics and Traumatology The Chinese University of Hong Kong Guangdong Engineering Laboratory of Biomaterials Additive Manufacturing

3D生物打印技术是一种基于传统3D打印技术发展起来的新兴技术。该技术可以把生物相容性材料、细胞或生物活性因子进行精准组装,为组织工程研究提供新方向。在众多3D生物打印技术中,光固化3D生物打印技术在组织工程研究领域发挥着重要作... 详细信息

3D生物打印技术是一种基于传统3D打印技术发展起来的新兴技术。该技术可以把生物相容性材料、细胞或生物活性因子进行精准组装,为组织工程研究提供新方向。在众多3D生物打印技术中,光固化3D生物打印技术在组织工程研究领域发挥着重要作用,而光固化3D生物打印技术的成功应用又与生物材料的光固化特性不可分割。在可见光固化材料中,光交联水凝胶因聚合速度快、时间和结构可控的特点而极具研究价值和应用潜能。众所周知,光聚合反应通常由紫外线或可见光引发。然而,紫外线用于3D生物打印可能会造成细胞损伤,影响细胞的活力。而可见光在生物安全性方面具有独特的优势,所以,将可见光交联技术应用在3D生物打印领域极具应用前景。本文回顾了目前可应用的由可见光引发的3D生物打印技术,并对可见光交联生物墨水的交联机理、可见光引发剂类型和生物医学应用进行了介绍。本文最后对可见光引发的3D生物打印设备及水凝胶目前在生物医学领域应用中存在的挑战和前景进行了讨论。

关键词：医用增材制造生物墨水组织工程 3D生物打印

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Quality of Life in Men Treated for Early Prostate Cancer: A Prospective Patient Preference Cohort Study

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Journal of Cancer Therapy 2011年第4期2卷 448-457页

作者： Carmel Nirupa Anandadas Susan Elizabeth Davidson Noel William Clarke Stephen Charles William Brown John Paul Logue Lynne Gilmore Richard Swindell Gerald Nicholas Collins Patrick Henry O’Reilly Guy David Wemyss-Holden Maurice Waiming Lau Pradip Madhukar Javle Vijay alini Chandi Ramani Richard James Brough James Pinson Wylie Richard Andrew Cowan 不详

Objectives: In 1997, a study was launched to investigate the treatment of early prostate cancer. Using a patient preference design, health-related quality-of-life (HRQOL) and disease specific HRQOL was assessed prospectively to compare men undergoing radical prostatectomy (RP), hypo-fractionated conformal radiotherapy (CRT) or brachytherapy (BT). Methods: Patients with localised prostate cancer were counselled by a urological surgeon, clinical oncologist and specialist uro-oncology nurse. Patients received treatment according to individual preference. 430 men chose and received RP (n = 217), CRT (n = 161) and BT (n = 52). 354 (82%) completed pre-treatment RAND 36-Item Short-Form Health survey version-2 (SF36v2) and University of California, Los Angeles Prostate cancer index (UCLA-PCI) questionnaires. HRQOL score changes from baseline to 24 months were compared using Kruskall-Wallis test. Results: Pre-treatment, the CRT cohort scored lower for physical function (p = 0.0029) and general health perception (p = 0.0021). The BT cohort reported better baseline scores for urinary function (p = 0.0291), urinary bother (p = 0.0030), sexual function (p = 0.0009) and bowel bother (p = 0.0063). At 24 months, bowel function was similar for CRT and BT but both modalities were worse than RP (p = 0.0010). Urinary continence deteriorated most following RP (p < 0.0001) but BT had worse urinary bother (p = 0.0153). Sexual function deteriorated most following RP and BT (p < 0.0005). Percentages of patients achieving erections adequate for sexual activity (from baseline to 24 months) were 66% to 29% for RP, 62% to 49% for CRT and 88% to 65% for BT. Conclusion: This data demonstrates significant differences in disease specific quality-of-life between RP, CRT and BT and should be available for men with early prostate cancer making treatment decisions.

关键词： Early Prostate Cancer Quality of Life Patient Preference Prostatectomy Hypo-Fractionated Radiotherapy Brachytherapy

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