Marginal sealing around integral bilayer scaffolds for repairing osteochondral defects based on photocurable silk hydrogels

Abstract

Osteochondral repair remains a major challenge in current clinical practice despite significant advances in tissue engineering. In particular, the lateral integration of neocartilage into surrounding native cartilage is a difficult and inadequately addressed problem that determines the success of tissue repair. Here, a novel design of an integral bilayer scaffold combined with a photocurable silk sealant for osteochondral repair is reported. First, we fabricated a bilayer silk scaffold with a cartilage layer resembling native cartilage in surface morphology and mechanical strength and a BMP-2-loaded porous subchondral bone layer that facilitated the osteogenic differentiation of BMSCs. Second, a TGF-β3-loaded methacrylated silk fibroin sealant (Sil-MA) exhibiting biocompatibility and good adhesive properties was developed and confirmed to promote chondrocyte migration and differentiation. Importantly, this TGF-β3-loaded Sil-MA hydrogel provided a bridge between the cartilage layer of the scaffold and the surrounding cartilage and then guided new cartilage to grow towards and replace the degraded cartilage layer from the surrounding native cartilage in the early stage of knee repair. Thus, osteochondral regeneration and superior lateral integration were achieved in vivo by using this composite. These results demonstrate that the new approach of marginal sealing around the cartilage layer of bilayer scaffolds with Sil-MA hydrogel has tremendous potential for clinical use in osteochondral regeneration.

Directed Regeneration of Osteochondral Tissue by Hierarchical Assembly of Spatially Organized Composite Spheroids

“…[ 54 ] As a result, the more calcified tissue and mature bone formation were found in the implanted area than the control groups without growth factors; however, empty fissures were observed in the cartilage area and connective tissues were also found in the subchondral bone area. [ 54 ] The deficient regeneration might be caused by the off‐targeted and inconsistent delivery of growth factors. [ 55 ] Unlike these approaches, the biphasic construct developed in our approach contained the composite spheroids (BS and TS), which have specifically given the inductive signals to stem cells in a stable manner with reduced amount of BMP‐2 (totally 1.8 µg) or TGF‐ β 3 (totally 0.9 µg) from the inside of a spheroid, showed the more effective differentiation of stem cells (Figure 3 ), continuously reproduced the growth factors (Figure S4 , Supporting Information), and finally succeeded in volumetric regeneration of critical sized osteochondral defect (Figure 7 ).…”

“…[ 80 ] To solve this limitation, MSC spheroids were pre‐positioned within carriers such as alginate/hyaluronic hydrogel, decellularized matrix, and 3D‐printed PCL scaffold before transplantation. [ 53 , 54 ] However, the regeneration was not improved dramatically because the spheroids could not be differentiated specifically into cartilage or bone without induction of osteogenic or chondrogenic growth factors. [ 83 ] In our previous study, we demonstrated that both instructive growth factors and carriers for spheroids were necessary for formation of mature bone in a mouse calvarial bone defect.…”

Instructive cartilage regeneration modalities with advanced therapeutic implantations under abnormal conditions

“…created a photocurable methacrylate silk fibroin to seal the gap between the bi-layered silk scaffold and adjacent cartilage. Under the high bioactivity of this sealing hydrogel, native BM-MSCs migrated to scaffold-native tissue interface to promote cartilage regeneration [ 64 ]. Recently, several bi-layered scaffolds, including Agili-C™, BioMatrix CRD®, TruFit® Plug, OsseoFit® Plug, and so forth, for the osteochondral defect treatment have been on the stage for clinical trials or approved for clinical application [ 46 ].…”

Scaffold-Based Tissue Engineering Strategies for Osteochondral Repair

“…Crystals are removed subsequently The electrohydrodynamic technique, also known as rapid prototyping or solid freeform fabrication, is classified into seven processes: vat photopolymerization, material jetting, material extrusion, powder bed fusion, directed energy deposition, sheet lamination and binder jetting. Tang et al (2016); Gibbs et al (2014) technology (Wu et al, 2021). The lyophilized silk powder was first mixed with hexafluoroisopropanol (HFIP) solution with or without sucrose particles in a silicone mold.…”

“…The chitosan/alginate gel was treated through a series of steps for scaffold fabrication such as lyophilization, cross-linking and elution. Wu et al evaluated the efficacy of bilayered silk scaffolds loaded with TGF-β3/BMP-2 for osteochondral defect repair in rabbits aided by the solvent casting/particulate leaching technology ( Wu et al, 2021 ). The lyophilized silk powder was first mixed with hexafluoroisopropanol (HFIP) solution with or without sucrose particles in a silicone mold.…”