In Situ Articular Cartilage Regeneration through Endogenous Reparative Cell Homing Using a Functional Bone Marrow-Specific Scaffolding System

Abstract

In situ tissue regeneration by homing endogenous reparative cells to the injury site has been extensively researched as a promising alternative strategy to facilitate tissue repair. In this study, a promising scaffolding system DCM-RAD/ SKP, which integrated a decellularized cartilage matrix (DCM)-derived scaffold with a functionalized self-assembly Ac-(RADA) 4 -CONH 2 /Ac-(RA-DA) 4 GGSKPPGTSS-CONH 2 (RAD/SKP) peptide nanofiber hydrogel, was designed for repairing rabbit osteochondral defect. In vitro experiments showed that rabbit bone marrow stem cells migrated into and have higher affinity toward the functional scaffolding system DCM-RAD/SKP than the control scaffolds. One week after in vivo implantation, the functional scaffolding system DCM-RAD/SKP facilitated the recruitment of endogenous mesenchymal stem cells within the defect site. Moreover, gene expression analysis indicated that the DCM-RAD/SKP promoted chondrogenesis of the recruited cells. In vivo results showed that the DCM-RAD/SKP achieved superior hyaline-like cartilage repair and successful subchondral bone reconstruction. By contrast, the control groups mostly led to fibrous tissue repair. These findings indicate that the DCM-RAD/SKP can recruit endogenous stem cells into the site of cartilage injury and promote differentiation of the infiltrating cells into the chondrogenic lineage, holding great potential as a one-step surgery strategy for cartilage repair.

Advances in intracellular delivery through supramolecular self-assembly of oligonucleotides and peptides

“…On self-assembling, hydrophilic residues of amino acids are located toward the exterior water phase while hydrophobic residues are buried in the core, contributing to the unique structures of β sheeted materials that are effective for small molecule or gene delivery applications (Figure 7A) 108. The first β sheet nanomaterial, RADA 16, has been utilized for drug delivery 109,110, regenerative medicine (neural stem cell differentiation) 111, in vivo brain damage repair and bone regeneration 112,113. The SAPs that form the nanostructures with a high aspect ratio, like ribbons, fibrils, and fibers, with varied numbers of β sheets in the final structures.…”

Advances of nanotechnology in osteochondral regeneration

“…Functionalized self‐assembly polymers or peptide nanobased scaffolds have been prepared for osteochondral regeneration (Hrabchak et al, ; X. Sun et al, ). However, the drawbacks of the large time consumption and instability limit the application of the self‐assembly method in the clinic.…”

“…Among these methods, self-assembly and chemical foaming are commonly used for the fabrication of scaffolds with inner structures for tissue engineering. Functionalized self-assembly polymers or peptide nanobased scaffolds have been prepared for osteochondral regeneration (Hrabchak et al, 2010;X. Sun et al, 2018).…”

Injectable Cholesterol‐Enhanced Stereocomplex Polylactide Thermogel Loading Chondrocytes for Optimized Cartilage Regeneration

“…Typically, the engineered cartilage constructs are either grown in vitro or formed in situ by the combination of cells, scaffolds, and bioactive stimuli . Natural or synthetic polymer‐based scaffolds are required to mimic the extracellular matrix (ECM) to support the growth of chondrocytes and the hyaline‐like cartilage formation in 3D culture .…”