A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour. Building suitable mechanical stimuli using feasible scaffold material and moderate mechanical loading is critical in bone tissue engineering for bone repair. However, the detailed mechanism of the mechanical regulation remains ambiguous. In addition, TRPV4 is involved in bone development. Therefore, this study aims to construct a viscoelastic hydrogel combined with dynamic compressive loading and investigate the effect of the dynamic mechanical environment on the osteogenic differentiation of stem cells and bone repair in vivo. The role of TRPV4 in the mechanobiology process was also assessed. A sodium alginate-gelatine hydrogel with adjustable viscoelasticity and good cell adhesion ability was obtained. The osteogenic differentiation of BMSCs was obtained using the fast stress relaxation hydrogel and a smaller compression strain of 1.5%. TRPV4 was activated in the hydrogel with fast stress relaxation time, followed by the increase in intracellular Ca²⁺ level and the activation of the Wnt/β-catenin pathway. The inhibition of TRPV4 induced a decrease in the intracellular Ca²⁺ level, down-regulation of β-catenin, and reduced osteogenesis differentiation of BMSCs, suggesting that TRPV4 might be the key mechanism in the regulation of BMSC osteogenic differentiation in the viscoelastic dynamic mechanical environment. The fast stress relaxation hydrogel also showed a good osteogenic promotion effect in the rat femoral defect model. The dynamic viscoelastic mechanical environment significantly induced the osteogenic differentiation of BMSCs and bone regeneration, which TRPV4 being involved in this mechanobiological process. Our study not only provided important guidance for the mechanical design of new biomaterials, but also provided a new perspective for the understanding of the interaction between cells and materials, the role of mechanical loading in tissue regeneration, and the use of mechanical regulation in tissue engineering.

Lumbar total disc replacement (TDR) has shown satisfactory clinical outcomes with few complications and reoperations at short-term follow-up, but the mid- to long-term results are not clear. The objective of this study was to evaluate the mid- to long-term clinical outcomes of artificial TDR for lumbar degenerative disc diseases. A systematic search was conducted using the PubMed database to identify studies of TDR surgery that included at least 3 years of follow-up. The search keywords were as follows: lumbar, total disc replacement, and arthroplasty. The following data were extracted: patient demographics, visual analogue scale (VAS) and Oswestry disability index (ODI) scores, satisfactory rate, clinical success rate, complications, and reoperations. Thirteen studies, including eight prospective studies and five retrospective studies, met the criteria. A total of 946 patients were identified who reported at least 3 years of follow-up results. The artificial prostheses in these studies were ProDisc-L, Charité, AcroFlex, Maverick, and XL TDR. Patients with lumbar TDR demonstrated significant improvements in VAS scores of 51.1 to 70.5% and of − 15.6 to − 44.4 for Oswestry disability index (ODI) scores at the last follow-up. Patient satisfaction rates were reported in eight studies and ranged from 75.5 to 93.3%. Complication rates were reported in 11 studies, ranging from 0 to 34.4%. The overall reoperation rate was 12.1% (119/986), ranging from 0 to 39.3%, with eight of the 13 studies reporting a reoperation rate of less than 10%. This review shows that lumbar TDR effectively results in pain relief and an improvement in quality of life at mid- to long-term follow-up. Complication and reoperation rates were acceptable. However, this study did not provide sufficient evidence to show that lumbar TDR is superior to fusion surgery. To answer that question, a greater number of high-quality randomized controlled trials (RCTs) are needed.