The preparation and application of calcium phosphate biomedical composites in filling of weight-bearing bone defects.

Nowadays, artificial bone materials have been widely applied in the filling of non-weight bearing bone defects, but scarcely ever in weight-bearing bone defects. This study aims to develop an artificial bone with excellent mechanical properties and good osteogenic capability. Firstly, the collagen-thermosensitive hydrogel-calcium phosphate (CTC) composites were prepared as follows: dissolving thermosensitive hydrogel at 4 °C, then mixing with type I collagen as well as tricalcium phosphate (CaP) powder, and moulding the composites at 37 °C. Next, the CTC composites were subjected to evaluate for their chemical composition, micro morphology, pore size, Shore durometer, porosity and water absorption ability. Following this, the CTC composites were implanted into the muscle of mice while the 70% hydroxyapatite/30% ß-tricalcium phosphate (HA/TCP) biomaterials were set as the control group; 8 weeks later, the osteoinductive abilities of biomaterials were detected by histological staining. Finally, the CTC and HA/TCP biomaterials were used to fill the large segments of tibia defects in mice. The bone repairing and load-bearing abilities of materials were evaluated by histological staining, X-ray and micro-CT at week 8. Both the CTC and HA/TCP biomaterials could induce ectopic bone formation in mice; however, the CTC composites tended to produce larger areas of bone and bone marrow tissues than HA/TCP. Simultaneously, bone-repairing experiments showed that HA/TCP biomaterials were easily crushed or pushed out by new bone growth as the material has a poor hardness. In comparison, the CTC composites could be replaced gradually by newly formed bone and repair larger segments of bone defects. The CTC composites trialled in this study have better mechanical properties, osteoinductivity and weight-bearing capacity than HA/TCP. The CTC composites provide an experimental foundation for the synthesis of artificial bone and a new option for orthopedic patients.

Exercise Promotes the Osteoinduction of HA/ß-TCP Biomaterials via the Wnt Signaling Pathway.

To investigate the osteoinductive mechanism triggered by hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) biomaterials in mice which keep exercising. Methods: The HA/ß-TCP biomaterials were implanted in the muscle of bilateral thighs (non-osseous sites) of eighty Balb/C mice. All animals were then randomly divided into 4 groups (n = 20). In group 1 (negative control group), the mice were fed routinely. In group 2 (running group), all mice were put on a treadmill which was set to a 60-degree incline. The mice ran 20 min thrice each day. A 5-minute break was included in the routine from day three onwards. In group 3 (weight-bearing group), all mice underwent weight-bearing running. The mice in this group performed the same routine as group 2 while carrying 5 g rubber weights. In group 4 (positive control group), dexamethasone was injected in the implanted sites of the biomaterials from the day of the operation. All mice were injected once per week and received a total of 8 injections. One and eight weeks after surgery, the blood serum was collected to detect inflammatory and immunological factors by ELISA. In addition to this, biomaterial specimens were obtained to observe inflammatory and osteogenic levels via histological staining and to facilitate analysis of the osteogenic mechanism by Western Blot. Results: The inflammation indexes caused by surgery were alleviated through running or weight-bearing running: The tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were significantly reduced in groups 2 and 3 at week 8. Exercise also enhanced the secretion of interferon-γ (IFN-γ) in mice; this can strengthen their immunity. The new bone tissues were observed in all groups; however, the area percentage of new bone tissues and the number of osteoblasts were highest in the weight-bearing group. Furthermore, the key proteins of wingless/integrated (Wnt) signaling pathway, Wnt1, Wnt3a, and ß-catenin, were up-regulated during osteoinduction. This up-regulation activated runt-related transcription factor-2 (Runx2), increased the expression of osteopontin (OPN) and osteocalcin (OCN). Conclusion: Weight-bearing exercise can promote the bone and bone marrow formation through the Wnt signaling pathway: Observations documented here suggest that the proper exercise is beneficial to the recovery of bone damage.