Osseointegration Model For Porous Scaffolds Based On Immunomodulation

Bone injuries caused by an ageing population,environmental degradation,accidental trauma and oncological diseases are clinically important causes of loss of physical function and reduced standard of living for patients.Artificial porous bone scaffolds have become a major means of treating bone injuries due to their controlled mechanical strength,excellent biocompatibility and advanced processing and manufacturing methods.The immune system has an important role in bone regeneration in porous scaffolds,but this process involves complex physiological processes such as inflammatory response,migration and differentiation of cells,and angiogenesis,making it difficult to reveal the mechanisms of interaction of various factors through in vivo and ex vivo experiments.By simplifying the physiological processes and predicting quantitative relationships between various cell behaviors at different scales,mathematical models of bone tissue regeneration can help to resolve the physiological mechanisms and provide a basis for clinical hypothesis testing.In this paper,a computational model of osseointegration in porous scaffolds based on immune modulation is developed to describe the bone regeneration process in porous scaffolds using a continuous-discrete coupled mathematical model.The model takes into account the influence of the inflammatory response on the outcome of bone deposition,mainly including physiological processes such as macrophage polarization,inflammation-promoted cell recruitment,crosstalk between macrophages and mesenchymal stem cells,growth factorpromoted osteogenic differentiation,vascular regeneration and oxygen supply.The calculations are consistent with animal experiments in the literature,and the model can predict the role of various cellular activities in the bone regeneration process more accurately.The calculations show that by introducing the process of acute inflammatory regression of bone implantation into the model,the change in cytokine type and distribution in the scaffold with immune status and the effect on cell recruitment,proliferation,migration and differentiation are simulated;the calculations show that the crosstalk mechanism of MSCs on macrophages increases the rate of polarization of M2 state macrophages and enhances the total amount of bone deposition;the addition of The mechanism of growth factors on the differentiation probability of osteoblasts in the model led to the tendency of osteoblasts in the scaffold to differentiate and deposit at locations with high concentrations of growth factors,and the calculated results showed a more concentrated distribution of bone volume,which was more consistent with the results of animal experiments on bone ingrowth.Finally,a mathematical model was used to initially explore the process of bone regeneration within the scaffold under chronic inflammatory conditions.The calculated results showed that the chronic inflammatory environment led to a greater extent of bone deposition and a lower amount of bone deposition,which is consistent with the result that chronic inflammation in vivo leads to osteoporosis.In addition,the effect of micro motion on the immune environment prior to scaffold implantation was modelled,whereby micro motion led to a temporary increase in inflammatory cytokine levels,which in turn promoted stem cell recruitment and increased bone ingrowth within the scaffold,and the calculated results were consistent with the clinical results.Calculated results for the decrease in bone volume with age and the increase in bone-like material with age in a model of human bone ingrowth of different ages and sexes based on the mineralization time parameters provided by bone histomorphology were also consistent with the actual findings.