Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: In vitro and in vivo assessment of biological performance

Abstract

Novel porous bilayered scaffolds, fully integrating a silk fibroin (SF) layer and a silk-nano calcium phosphate (silk-nanoCaP) layer for osteochondral defect (OCD) regeneration, were developed. Homogeneous porosity distribution was achieved in the scaffolds, with calcium phosphate phase only retained in the silk-nanoCaP layer. The scaffold presented compressive moduli of 0.4MPa in the wet state. Rabbit bone marrow mesenchymal stromal cells (RBMSCs) were cultured on the scaffolds, and good adhesion and proliferation were observed. The silk-nanoCaP layer showed a higher alkaline phosphatase level than the silk layer in osteogenic conditions. Subcutaneous implantation in rabbits demonstrated weak inflammation. In a rabbit knee critical size OCD model, the scaffolds firmly integrated into the host tissue. Histological and immunohistochemical analysis showed that collagen II positive cartilage and glycosaminoglycan regeneration presented in the silk layer, and de novo bone ingrowths and vessel formation were observed in the silk-nanoCaP layer. These bilayered scaffolds can therefore be promising candidates for OCD regeneration.

In vitro and in vivo studies of a novel bacterial cellulose-based acellular bilayer nanocomposite scaffold for the repair of osteochondral defects

“…The subchondral bone formation may have resulted from osteoconductive property of nanocomposite BC-HA activated with BMP-2. This is in conjunction with previous reports 5,47,48 where subchondral bone formation is reported to enhance regeneration of the articular cartilage. In the current in vivo study, the size of the modified BC scaffold was significantly reduced at 3 months, indicating biodegradative resorption and integration in the surrounding tissue.…”

“…This purpose warrants the development of bioactive scaffolds with spatially presented biological cues for repair of OCD. [5][6][7] Although an ideal bioactive scaffold helps in the repair of OCD, its combination with microfracture therapy is thought to augment the healing process. 8,9 Microfracture therapy involves drilling in the osteochondral lesion that aids in the recruitment of bone marrow stem cells.…”

“…As of now, autologous implantation of chondrocytes or osteochondral plugs is the only surgical treatment available for the restoration of the damaged tissue. [3][4][5] The limitations associated with autologous implantation include the need for two surgeries, the extended period required for tissue recovery and maturation. 4 As an alternative method, allogenous cell-based strategies are now emerging, which employ invasive techniques for the isolation of cells and their ex vivo expansion.…”

Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces

“…Recently, bilayered scaffolds have been investigated, where each layer of the scaffold represents a different tissue. [54][55][56] Although a better representation of the complex interface tissue, this strategy does not account for the interface region. [19] More recently, multi-layered scaffolds consisting of three or more layers have been designed.…”

Biofunctional Ionic-Doped Calcium Phosphates: Silk Fibroin Composites for Bone Tissue Engineering Scaffolding

“…Composite scaffolds of SF/TCP and SF/ionic-doped TCP were prepared with blend ratios of 70/30 SF/β-TCP (w/w) using a particulate leaching technique followed by freeze-drying [Yan et al, 2013b[Yan et al, , 2015b. Firstly, β-TCP powders were added to SF solution with fast stirring for 2 min.…”