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| 1 | A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration显示文摘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 materials.Here,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 resolution.Our 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 fibrosis.Moreover,we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling pathways.Heterogeneity of MSCs was also demonstrated.In 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 process.These findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds,providing new insights for the improvement of osteogenic biomaterials.This 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. | 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 | 2022 | Bioactive Materials2022，7，3： | 3 |
| 2 | Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration显示文摘It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear.This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds.Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7,14,or 21 days.At the predetermined time points,culture supernatant was collected for inflammatory mediator detection,and gene expression was analyzed by qRT-PCR.The results showed that the expression of inflammatory mediators(IL1B and IL8)was downregulated(p<0.05)and the expression of ALP(p<0.01)and COL1A1(p<0.05)was upregulated under mechanical loading.The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds(ECM-based scaffolds).Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization.The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers(Arginase 1 and Mrc1,p<0.05)of macrophages in vitro and increased bone volume/total volume ratio in vivo.Overall,these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs.Besides,the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo.Mechanical loading may be a promising biofabrication strategy for bone biomaterials. | Penghui Zhang Xizhe Liu Peng Guo Xianlong Li Zhongyuan He Zhen Li Martin J.Stoddart Sibylle Grad Wei Tian Dafu Chen Xuenong Zou Zhiyu Zhou Shaoyu Liu | 2021 | Bioactive Materials2021，6，10： | 2 |
| 3 | Functionalized Hydrogels for Articular Cartilage Tissue Engineering显示文摘Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage adequately.With rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC repair.Finally,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation. | Liangbin Zhou Peng Guo Matteo D’Este Wenxue Tong Jiankun Xu Hao Yao Martin J.Stoddart Gerjo J.V.M.van Osch Kevin Ki-Wai Ho Zhen Li Ling Qin | 2022 | Engineering2022，8，6： | 1 |
| 4 | A culture model to analyze the acute biomaterial-dependent reaction of human primary neutrophils in vitro显示文摘Neutrophils play a pivotal role in orchestrating the immune system response to biomaterials,the onset and resolution of chronic inflammation,and macrophage polarization.However,the neutrophil response to biomaterials and the consequent impact on tissue engineering approaches is still scarcely understood.Here,we report an in vitro culture model that comprehensively describes the most important neutrophil functions in the light of tissue repair.We isolated human primary neutrophils from peripheral blood and exposed them to a panel of hard,soft,naturally-and synthetically-derived materials.The overall trend showed increased neutrophil survival on naturally derived constructs,together with higher oxidative burst,decreased myeloperoxidase and neutrophil elastase and decreased cytokine secretion compared to neutrophils on synthetic materials.The culture model is a step to better understand the immune modulation elicited by biomaterials.Further studies are needed to correlate the neutrophil response to tissue healing and to elucidate the mechanism triggering the cell response and their consequences in determining inflammation onset and resolution. | Marinus A.Wesdorp Andrea Schwab Ezgi Irem Bektas Roberto Narcisi David Eglin Martin J.Stoddart Gerjo J.V.M.Van Osch Matteo D’Este | 2023 | Bioactive Materials2023，，2： | 0 |
| 5 | Function-oriented design:A novel strategy for advanced biomedical materials显示文摘It has always been a dream to construct tissues and even organs for transplantation to replace those with defects caused by diseases or injuries.Tissue engineering is another milestone in the developmental history of life science after cellular and molecular bioscience.Nevertheless,despite decades of rapid de-velopment,tissue-engineered biomaterials have not been widely used clinically.Biomaterials constructed by physical and chemical methods have lots of difficulty in precisely mimicking the macroscopic and mi-croscopic structures of human tissues.The ultimate way to build organoid tissue for regeneration is to enable the cells to take the initiative and build suitable functions.Based on the thoughts of tissue engi-neering,organoid technology holds great potential as a research tool for a wide range of fields,including developmental biology,disease pathology,cell biology,precision medicine,and drug toxicity and efficacy testing.This technology also holds tremendous potential for regenerative medicine,as organoids present the possibility for autologous and allogeneic cell therapy through the replacement of damaged or dis-eased tissues with organoid-propagated tissue or stem cell populations.In this review work,we briefly outlook the development history of organoid technology,summarize the current bottlenecks and the un-derlying reasons,and propose the unified term“function-oriented design in tissue engineering”,a new topic that may provide a solution to overcome these bottlenecks. | Zhiyu Zhou Wentao Wang Jianmin Wang Hongshui Wang Yi Xia Wei Zhang Yuxiao Lai Xiao Lin Yongcan Huang Xuenong Zou Martin J.Stoddart Zhen Li Wei Tian Shaoyu Liu Xinbao Wu Manman Gao Junhong Li Lei Yang Dafu Chen | 2023 | Journal of Materials Science & Technology2023，，14： | 0 |
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