Role of hypoxia inducible factor 1α in cobalt nanoparticle induced cytotoxicity of human THP-1 macrophages

Cobalt is one of the main components of metal hip prostheses and cobalt nanoparticles(CoNPs)produced from wear cause inflammation,bone lyses and cytotoxicity at high concentrations.Cobalt ions mimic hypoxia in the presence of normal oxygen levels,and activate hypoxic signalling by stabilising hypoxia inducible transcription factor 1α(HIF1α).This study aimed to assess in vitro the functional role of HIF1αin CoNP induced cellular cytotoxicity.HIF1α,lysosomal pH,tumour necrosis factorαand interleukin 1βexpression were analysed in THP-1 macrophages treated with CoNP(0,10 and 100μg/mL).HIF1αknock out assays were performed using small interfering RNA to assess the role of HIF1αin CoNP-induced cytotoxicity.Increasing CoNP concentration increased lysosomal activity and acidity in THP-1 macrophages.Higher doses of CoNP significantly reduced cell viability,stimulated caspase 3 activity and apoptosis.Reducing HIF1αactivity increased the pro-inflammatory activity of tumour necrosis factorαand interleukin 1β,but had no significant impact on cellular cytotoxicity.This suggests that whilst CoNP promotes cytotoxicity and cellular inflammation,the apoptotic mechanism is not dependent on HIF1α.

Efficient calculation of fluid-induced wall shear stress within tissue engineering scaffolds by an empirical model

Mechanical stimulation,such as fluid-induced wall shear stress(WSS),is known that can influence the cellular behaviours.Therefore,in some tissue engineering experiments in vitro,mechanical stimulation is applied via bioreactors to the cells in cell culturing to study cell physiology and pathology.In 3D cell culturing,porous scaffolds are used for housing the cells.It is known that the scaffold porous geometries can influence the scaffold permeability and internal WSS in a bioreactor(such as perfusion bioreactor).To calculate the WSS generated on cells within scaffolds,usually computational fluid dynamics(CFD)simulation is needed.However,the limitations of the computational method for WSS calculation are:(i)the high time cost of the CFD simulation(in particular for the highly irregular geometries);(ii)accessibility to the CFD model for some cell culturing experimentalists due to the knowledge gap.To address these limitations,this study aims to develop an empirical model for calculating the WSS based on scaffold permeability.This model can allow the tissue engineers to efficiently calculate the WSS generated within the scaffold and/or determine the bioreactor loading without performing the computational simulations.

The emergence of AI tools in scientific writing and research

Biomaterials Translational is now in its third year since its establishment.On March 19,the first virtual forums in 2023 on‘Advanced Technology for Biomaterial Research’hosted by Biomaterials Translational received a great response.The forum covered topics including angiogenesis of biomaterials presented by Professor Jake Barralet,McGill University,Canada,and a new lasermicrotome technology from Dr.Heiko Rechter,LLS ROWIAK LaserLabSolutions,Germany.Lasermicrotome and its related platform are expected to have wide applications for histology,pathology,and tissue/biomaterial interfaces,as shown in the cover art.

优化底物酶及冻存剂组成对软骨细胞增殖力及活力的影响

[目的]本文研究的目的在于找到软骨细胞分离的合适方法及优化冰冻保存软骨组织的配方。[方法]来源于骨关节炎膝关节置换术的软骨标本被用于本次试验,采用300或400 u/ml II型胶原酶(CTII-1或2)进行软骨细胞体外分离,保存在不同组成的冷冻剂中,进行梯度冷却并保存在液氮中48 h,随后进行软骨细胞活力及增殖潜力的测定。[结果]CTII-1较CTII-2更能分离出高活力的软骨细胞(P<0.05),并且300或400 u/ml的底物酶浓度比较合适。10%DMSO+90%FCS是一种比较合适的冰冻保护剂,能够最大程度保留软骨细胞的增殖潜力与活力,并且毒副作用小。[结论]通过相关的优化措施诸如软骨细胞体外分离底物酶以及冰冻保护剂的组成,从关节软骨组织中分离具有高增殖潜力的活力软骨细胞是一种可行的方法。

Three-dimensional biofabrication of an aragoniteenriched self-hardening bone graft substitute and assessment of its osteogenicity in vitro and in vivo

A self-hardening three-dimensional(3D)-porous composite bone graft consisting of 65 wt%hydroxyapatite(HA)and 35 wt%aragonite was fabricated using a 3D-Bioplotter®.New tetracalcium phosphate and dicalcium phosphate anhydrous/aragonite/gelatine paste formulae were developed to overcome the phase separation of the liquid and solid components.The mechanical properties,porosity,height and width stability of the end products were optimised through a systematic analysis of the fabrication processing parameters including printing pressure,printing speed and distance between strands.The resulting 3D-printed bone graft was confirmed to be a mixture of HA and aragonite by X-ray diffraction,Fourier transform infrared spectroscopy and energy dispersive X-ray spectroscopy.The compression strength of HA/aragonite was between 0.56 and 2.49 MPa.Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay in vitro.The osteogenicity of HA/aragonite was evaluated in vitro by alkaline phosphatase assay using human umbilical cord matrix mesenchymal stem cells,and in vivo by juxtapositional implantation between the tibia and the anterior tibialis muscle in rats.The results showed that the scaffold was not toxic and supported osteogenic differentiation in vitro.HA/aragonite stimulated new bone formation that bridged host bone and intramuscular implants in vivo.We conclude that HA/aragonite is a biodegradable and conductive bone formation biomaterial that stimulates bone regeneration.Since this material is formed near 37°C,it will have great potential for incorporating bioactive molecules to suit personalised application;however,further study of its biodegradation and osteogenic capacity is warranted.The study was approved by the Animal Ethical Committee at Tongji Medical School,Huazhong University of Science and Technology(IACUC No.738)on October 1,2017.

Manufacturingartificial bone allografts:a perspective

Bone grafts have traditionally come from four sources:the patients’own tissue(autograft),tissue from a living or cadaveric human donor(allograft),animal donors(xenograft)and synthetic artificial biomaterials(ceramics,cement,polymers,and metal).However,all of these have advantages and drawbacks.The most commercially successful bone grafts so far are allografts,which hold 57%of the current bone graft market;however,disease transmission and scarcity are still significant drawbacks limiting their use.Tissue-engineered grafts have great potential,in which human stem cells and synthetical biomaterials are combined to produce bone-like tissue in vitro,but this is yet to be approved for widespread clinical practice.It is hypothesised that artificial bone allografts can be mass-manufactured to replace conventional bone allografts through refined bone tissue engineering prior to decellularisation.This review article aims to review current literature on(1)conventional bone allograft preparation;(2)bone tissue engineering including the use of synthetic biomaterials as bone graft substitute scaffolds,combined with osteogenic stem cells in vitro;(3)potential artificial allograft manufacturing processes,including mass production of engineered bone tissue,osteogenic enhancement,decellularisation,sterilisation and safety assurance for regulatory approval.From these assessments,a practical route map for mass production of artificial allografts for clinical use is proposed.

Additive manufacturing innovation for musculoskeletal tissue repair and regeneration:from bench to bedside

Additive manufacturing(AM)or three-dimensional(3D)printing is a technique that builds the 3D objects from a 3D digital model(either by a computer-aided design or by scanning the object)in a layer-by-layer fashion.There are seven categories of AM process as defined in the ISO/ASTM 52900:2021,1 based on their working principles.These include vat photopolymerization,powder bed fusion,material extrusion,binder jetting,directed energy deposition,material jetting,and sheet lamination.1 Over the past decades,AM technology has been exploited in many fields such as the medical,automotive,aerospace and industries.

Celebrating the 2^(nd)anniversary of Biomaterials Translational

December 2022 marks the 2^(nd)anniversary of the foundation of Biomaterials Translational.The birth of our journal occurred in the middle of the coronavirus disease 2019(COVID-19)pandemic.Despite the enormous disruption of human life and global interactions,the launch of Biomaterials Translational has drawn great attention from peers in the research fields of biomaterials science and translational medicine.Over the past 2 years,Biomaterials Translational has published nine issues with a total of 71 articles,including 17 research papers,39 literature reviews,15 view-point essays and editorials.The website can be visited at http://www.biomat-trans.com/,with 17,205 views of articles and 32,207 downloads(up to December 21,2022).Both citations and journal website visits have increased significantly since Biomaterials Translational was first included in PubMed in July 2022.

Skeletal interoception:an emerging area for musculoskeletal research

Little is known about the relationship between bone and brain;however,accumulated clinical and experimental evidence suggests that there is crosstalk and a bilateral dependence between the two organs.1 A recent review article published in Cell Metabolism highlights the importance of skeletal interoception and signifies a new era for musculoskeletal research.