Orthopedic implants are widely used for the treatment of bone defects caused by injury, infection, tumor and congenital diseases. However, poor osseointegration and implant failures still occur frequently due to the lack of direct contact between the implant and the bone. In order to improve the biointegration of implants with the host bone, surface modification is of particular interest and requirement in the development of implant materials. Implant surfaces that mimic the inherent surface roughness and hydrophilicity of native bone have been shown to provide osteogenic cells with topographic cues to promote tissue regeneration and new bone formation. A growing number of studies have shown that cell attachment, proliferation and differentiation are sensitive to these implant surface microtopography. This review is to provide a summary of the latest science of surface modified bone implants, focusing on how surface microtopography modulates osteoblast differentiation in vitro and osseointegration in vivo, signaling pathways in the process and types of surface modifications. The aim is to systematically provide comprehensive reference information for better fabrication of orthopedic implants.

Bone tissue displays a hierarchical organization. Mechanical environments influence bone mass and structure. This study aimed to explore the effects of different mechanical stimuli on growing bone properties at macro–micro–nano scales. Sixty five-week-old female Wistar rats were treadmill exercised at moderate intensity with the speed of 12 m/min, and then randomly divided into five groups according to weight-bearing level. After 8 weeks of experiment, femurs were harvested to perform multiscale tests. Bone formation was significantly increased by weight-bearing exercise, whereas bone resorption was not significantly inhibited. Trabecular and cortical bone mineral densities showed no significant increase by weight-bearing exercise. The microstructure of trabecular bone was significantly improved by 12% weight-bearing exercise. However, similar positive effects were not observed with further increase in weight-bearing levels. The nanomechanical properties of trabecular bone were not significantly changed by weight-bearing exercise. The macrostrength of whole femur and the nanomechanical properties of cortical bone significantly decreased in the 19% and 26% weight-bearing exercise groups. When rats ran on the treadmill at moderate intensity during growth period, additional 12% weight-bearing level could significantly increase bone formation, improve microstructure of trabecular bone, as well as maintain the structure and mechanical properties of cortical bone. Excessive weight-bearing level caused no positive effects on the trabecular bone microstructure and properties of cortical bone at all scales. In addition, increased weight-bearing level exerted no significant influence on trabecular and cortical bone mineral densities.

Osteogenic differentiation of cells has considerable clinical significance in bone defect treatment, and cell behavior is linked to extracellular matrix stiffness. This study aimed to determine how matrix stiffness affects cell morphology and subsequently regulates the osteogenic phenotype of osteogenesis precursor cells. Four PDMS substrates were prepared with stiffness corresponding to the elastic modulus ranging from 0.6 MPa to 2.7 MPa by altering the Sylgard 527 and Sylgard 184 concentrations. MC3T3-E1 cells were cultured on the matrices. Cell morphology, vinculin expression, and key osteogenic markers, Col I, OCN, OPN, and calcium nodule, were examined. The activity and expression level of Yes-associated protein (YAP) were evaluated. Results showed that cell spreading exhibited no correlation with the stiffness of matrix designed in this paper, but substratum stiffness did modulate MC3T3-E1 osteogenic differentiation. Col I, OPN, and OCN proteins were significantly increased in cells cultured on soft matrices compared with stiff matrices. Additionally, cells cultured on the 1:3 ratio matrices had more nodules than those on other matrices. Accordingly, cells on substrates with low stiffness showed enhanced expression of the osteogenic markers. Meanwhile, YAP expression was downregulated on soft substrates although the subcellular location was not affected. Our results provide evidence that matrix stiffness (elastic modulus ranging from 0.6 MPa to 2.7 MPa) affects the osteogenic differentiation of MC3T3-E1, but it is not that “the stiffer, the better” as showed in some of the previous studies. The optimal substrate stiffness may exist to promote osteoblast differentiation. Cell differentiation triggered by the changes in substrate stiffness may be independent of the YAP signal. This study has important implications for biomaterial design and stem cell-based tissue engineering.