Exploring the interconnectivity of biomimetic hierarchical porous Mg scaffolds for bone tissue engineering:Effects of pore size distribution on mechanical properties,degradation behavior and cell migration ability

Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration,blood vessels invasion and transport of nutrient and waste.However,efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems.In this work,biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting.Mg scaffold with better interconnectivity showed lower mechanical strength.Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration,pH value and osmolality of the degradation microenvironment due to the lower specific surface area.Nevertheless,the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit.Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size.In summary,design of interconnectivity in terms of pore size distribution could regulate mechanical strength,microenvironment in cell culture condition and cell migration potential,and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.

Effects of dynamic flow rates on degradation deposition behavior of Mg scaffold

Degradability of bone tissue engineering scaffold that matching the regeneration rate could allow a complete replacement of host tissue.However,the porous structure of biodegradable Mg scaffolds certainly generated high specific surface area,and the three-dimensional interconnected pores provided fast pervasive invasion entrance for the corrosive medium,rising concern of the structural integrity during the degradation.To clarify the structural evolution of the three-dimensional(3D)porous structure,semi-static immersion tests were carried out to evaluate the degradation performance in our previous study.Nevertheless,dynamic immersion tests mimicking the in vivo circulatory fluid through the interconnected porous structure have yet been investigated.Moreover,the effects of dynamic flow rates on the degradation deposition behavior of 3D porous Mg scaffolds were rarely reported.In this study,Mg scaffolds degraded at three flow rates exhibited different degradation rates and deposition process.A flow rate of 0.5 m L/min introduced maximum drop of porosity by accumulated deposition products.The deposition products provided limited protection against the degradation process at a flow rate of 1.0 m L/min.The three-dimensional interconnected porous structure of Mg scaffold degraded at 2.0 m L/min well retained after 14 days showing the best interconnectivity resistance to the degradation deposition process.The dynamic immersion tests disclosed the reason for the different degradation rates on account of flow rates,which may bring insight into understanding of varied in vivo degradation rates related to implantation sites.

Triptolide Inhibits Expression of Inflammatory Cytokines and Proliferation of Fibroblast-like Synoviocytes Induced by IL-6/sIL-6R-Mediated JAK2/STAT3 Signaling Pathway

Triptolide,a component of the Chinese herb Tripterygium wilfordii Hook F,has been proved to be effective in the treatment of rheumatoid arthritis(RA).However,its underlying mechanisms on RA have not yet been well established.We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes(FLS)induced by the complex of interleukin-6(IL-6)and the soluble form of the IL-6 receptor(sIL-6R).Furthermore,to clarify the underlying mechanisms,we treated FLS with the Janus-activated kinase 2(JAK2)inhibitor/signal transducer and activator of transcription 3(STAT3)activation blocker AZD1480.In this study,immunohistochemical staining was used to identify vimentin(+)and CD68(−)in FLS.The FLS proliferation was measured by cell proliferation assay,and the cell cycles were analyzed by flow cytometry.Furthermore,ELISA was used to detect the expression of the inflammatory factors in culture solution.The expression levels of p-JAK2,JAK2,p-STAT3 and STAT3 were investigated through Western blotting analysis.The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines,including IL-6,interleukin-1β(IL-1β)and vascular endothelial growth factor(VEGF).Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3.The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway.It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.

Fabrication of a bio-instructive scaffold conferred with a favorable microenvironment allowing for superior implant osseointegration and accelerated in situ vascularized bone regeneration via type H vessel formation

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone,most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells.Human umbilical vein endothelial cell-derived decellularized extracellular matrix(HdECM),which contains a collection of angiocrine biomolecules,has recently been demonstrated to mediate endothelial cells(ECs)-osteoprogenitors(OPs)crosstalk.We employed the HdECM to create a PCL(polycaprolactone)/fibrin/HdECM(PFE)hybrid scaffold.We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk,resulting in vascularized bone regeneration.Following implantation in a rat femoral bone defect,the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography(μ-AG)and micro-computational tomography(μ-CT).Based on the immunofluorescence studies,PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors.In addition,superior osseointegration was observed by a direct host bone-PCL interface,which was likely attributed to the formation of type H vessels.The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration.It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels,which could compensate for the inherent biological inertness of synthetic polymers.

Corrigendum to‘Fabrication of a bio-instructive scaffold conferred with a favorable microenvironment allowing for superior implant osseointegration and accelerated in situ vascularized bone regeneration via type H vessel formation’[Bioactive Materials,Volume 9(March 2022)Page 491-507]

The authors regret a mistake of funding numbers in the Acknowledgment Section failed to be corrected during proofreading.Below is the corrected funding statement in ACKNOWLEDGMENT SECTION:This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.82072415,81772354,81902189),Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201002),Science Technology Project of Guangzhou City(2019ZD15).