Patient-specific Scaffolds with a Biomimetic Gradient Environment for Articular Cartilage–Subchondral Bone Regeneration

Abstract

Functional articular repair is known to be hampered by tissue degradation, which occurs in the defective local inflammatory environment that is also characterized by disrupted angiogenesis. The advanced fabrication of scaffolds with designed chemical and physical cues, which provide a biomimetic environment for tissue regeneration, holds considerable promise to circumvent the problem and thus allows functional articular repair. Herein, we developed scaffolds with controllable shapes with hydroxybutyl chitosan (HBC) and oxidized chondroitin sulfate (OCS) hydrogels, whose chemical composition was similar to that of the cartilage extracellular matrix (ECM). By optimizing the concentration of OCS, the functional cross-linker, we achieved a hydrogel promoting proliferation, adhesion, and ECM formation of chondrocytes and inhibiting tube formation of endothelial cells. Using a hydration procedure and bioactivation of mesenchymal stem cells (MSCs), we obtained mesoporous silicate-doped calcium phosphate cement (MS/CPC) scaffolds with a bioactive surface similar to that of bones, with improved osteogenesis and vascularization properties. Personalized cartilage–subchondral repair scaffolds with stable combination were successfully fabricated based on the self-cross-linking properties of the Schiff-based HBC/OCS hydrogel and the macroporous structure of MS/CPC scaffolds with the aid of a 3D printing technique. This study proposes a strategy to design individualized tissue repair biomimetic gradient scaffolds. Further assessments of their osteochondral defect repair properties in vivo should be performed.

Zonally Stratified Decalcified Bone Scaffold with Different Stiffness Modified by Fibrinogen for Osteochondral Regeneration of Knee Joint Defect

“…In subchondral bone tissue, suitable angiogenesis can accelerate the bone formation . The vasculature provides nutrients, oxygen, and signaling cues to nearby cells that influence outcomes of subchondral bone regeneration .…”

“…In subchondral bone tissue, suitable angiogenesis can accelerate the bone formation. 41 The vasculature provides nutrients, oxygen, and signaling cues to nearby cells that influence outcomes of subchondral bone regeneration. 42 Considering that Fg could promote blood vessel formation, the expression of CD34 in the high-stiffness layer of the Fg + SDBM group was examined.…”

Recent Advances in “Functional Engineering of Articular Cartilage Zones by Polymeric Biomaterials Mediated with Physical, Mechanical, and Biological/Chemical Cues”

“…Owing to diffusion of the HBC/OCS hydrogel through pores, a transition layer is also formed. [ 71 ] Although the feasibility of this approach to fabricate a 3D structure with a similar defect shape is demonstrated, the scaffold performance requires further investigation using a clinically relevant animal model besides subcutaneous implantation.…”

“…3D printing of cartilaginous structures with zonal configurations fosters the development of personalized engineered scaffolds. [71][72][73] For example, the combination of calcium phosphate cement (CPC) with mesoporous silica (MS) has been 3Dprinted according to the shape of the patient's injured site. The hydrogel based on hydroxybutyl chitosan (HBC) crosslinked with oxidized CS (OCS) is 3D-printed on top and the in vivo results after subcutaneous implantation of the scaffolds into the dorsal region of nude mice show that MS/CPC promotes angiogenesis and subchondral bone development.…”

Thermo-responsive injectable naringin-loaded hydrogel polymerised sodium alginate/bioglass delivery for articular cartilage

“…In the subchondral bone zone, joint–cartilage defects frequently happen. The joint cartilage is a form of hyaline cartilage that shows good elastic properties, low friction and hypertonicity and plays an essential role in maintaining collective motion (Vázquez-Portalatín et al., 2016 ; Ye et al., 2016 ; Li et al., 2020 ). Joint replacements are not suitable for younger and medium-aged people because of inadequate life expectancy in joints implantation.…”