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.

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.