A major limitation in the development of effective scaffolds for bone regeneration has been the limited vascularization of the regenerating tissue. Here, we propose the development of a novel calcium phosphate cement (CPC)-based scaffold combining the properties of mesoporous silica (MS) with recombinant human bone morphogenic protein-2 (rhBMP-2) to facilitate vascularization and osteogenesis. Specifically, the development of a custom MS/CPC paste allowed the three-dimensional (3D) printing of scaffolds with a defined macroporous structure and optimized silicon (Si) ions release profile to promote the ingrowth of vascular tissue at an early stage after implantation in support of tissue viability and osteogenesis. In addition, the scaffold microstructure allowed the prolonged release of rhBMP-2, which in turn significantly stimulated the osteogenesis of human bone marrow stromal cells in vitro and of bone regeneration in vivo as shown in a rabbit femur defect repair model. Thus, the combination MS/CPC/rhBMP-2 scaffolds might provide a solution to issues of tissue necrosis during the regeneration process and therefore might be able to be readily developed into a useful tool for bone repair in the clinic.

Biological regeneration of articular cartilage continues to be a challenge at present. Functional engineered implants with patient-specific sizes are difficult to achieve. The aim of this study is to fabricate a biocompatible cell-laden hydrogel with a designable structure. Covalent hydrogels were prepared with water soluble hydroxybutyl chitosan (HBC) and oxidized chondroitin sulfate (OCS) via a Schiff-base reaction. With the aid of three-dimensional (3D) bioprinted sacrificial molds, HBC/OCS hydrogel with various structures were obtained. After the material constituent optimization process, an injectable hydrogel with a uniform porous structure of 100 μm average pore size was developed to form macroporous hydrogel. In vitro and in vivo biocompatibility of optimized HBC/OCS hydrogel were also carefully assessed. The results indicated that human adipose-derived mesenchymal stem cells could be 3D cultured in HBC/OCS hydrogel maintaining good viability. Moreover, the hydrogels were found to trigger the least amount of pro-inflammatory gene expression of macrophage and to inhibit acute immune responses in 7 d. These results demonstrate the potential of HBC/OCS hydrogels as a cell delivery system for cartilage tissue engineering.