Multi-layered hydrogels with organization of various functional layers have been the materials of choice for biomedical applications. This review summarized the recent progress of multi-layered hydrogels according to their preparation methods: layer-by-layer self-assembly technology, step-wise technique, photo-polymerization technique and sequential electrospinning technique. In addition, their morphology and biomedical applications were also introduced. At the end of this review, we discussed the current challenges to the development of multi-layered hydrogels and pointed out that 3D printing may provide a new platform for the design of multi-layered hydrogels and expand their applications in the biomedical field.

The management of oral and maxillofacial tissue defects caused by tumors, trauma, and congenital or acquired deformities has been a major challenge for surgeons over the last few decades. Autologous tissue transplantation, the gold standard of tissue reconstruction, is a valid method for repairing the oral and maxillofacial functions and aesthetics. However, several limitations hinder its clinical applications including complications of donor sites, limited tissue volume, and uncertain long-term outcomes. Adipose-derived mesenchymal stem cells (ADMSCs) widely exist in adipose tissue and can be easily obtained through liposuction. Like the bone marrow-derived mesenchymal stem cells (BMSCs), ADMSCs also have the multi-pluripotent potencies to differentiate into osteoblasts, chondrocytes, neurons, and myocytes. Therefore, the multilineage capacity of ADMSCs makes them valuable for cell-based medical therapies. In recent years, researchers have developed many candidates of ADMSCs-based biomaterial scaffolds to cater for the needs of oral and maxillofacial tissue engineering due to their superior performance. This review presents the advances and applications of ADMSCs-based biomaterial scaffolds, and explores their tissue engineering prospects in oral and maxillofacial reconstructions.

Strontium-doped calcium phosphate-based biomaterials have gained increased recognition due to their beneficial effects on bone formation. However, the underlying mechanism is still not clear. In this study, we detected the calcification effects of strontium-based materials on osteoblasts in vitro and bone formation in vivo. The results showed that strontium may inhibit bone cell function in osteoblasts under a standard calcium concentration (1.8 mM) by both reducing alkaline phosphatase activity and inhibiting absorption of osteopontin and osteocalcin. In contrast, a high calcium concentration (9 mM) enhances the bone regeneration effect of strontium-based materials. Cultured osteoblasts underwent increased proliferation, calcification and alkaline phosphatase activity upon increasing calcium concentrations. An experimental animal model was utilized to simulate a high calcium concentration microenvironment in bone tissue and low calcium concentration in the subcutaneous part and the in vivo results are similar to the in vitro results. These findings suggest that strontium only promoted an anabolic effect on osteoblasts to enhance osteogenesis in a calcium rich microenvironment. Strontium would inhibit bone regeneration under a low dose of calcium in vivo. Therefore, strontium seems to be a potentially effective therapeutic option for bone regeneration in combination with a high concentration environment of calcium ions. These results would provide an in-depth knowledge of an ion-based bone tissue substitute for bone regeneration.