3D-Bioprinted Difunctional Scaffold for In Situ Cartilage Regeneration Based on Aptamer-Directed Cell Recruitment and Growth Factor-Enhanced Cell Chondrogenesis

Abstract

Articular cartilage (AC) lesions are fairly common but remain an obstacle for clinicians and researchers due to their poor self-healing capacity. Recently, a promising therapy based on the recruitment of autologous mesenchymal stem cells (MSCs) has been developed for the regeneration of full-thickness cartilage defects in the knee joint. In this study, a 3D-bioprinted difunctional scaffold was developed based on aptamer HM69mediated MSC-specific recruitment and growth factor-enhanced cell chondrogenesis. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized cartilage extracellular matrix and then mixed with gelatin methacrylate to form a photocrosslinkable bioink ready for 3D bioprinting. Together with the growth factor that promoted cell chondrogenic differentiation, the biodegradable polymer poly(ε-caprolactone) was further chosen to impart mechanical strength to the 3D bioprinted constructs. The difunctional scaffold specifically recruited MSCs, provided a favorable microenvironment for cell adhesion and proliferation, promoted chondrogenesis, and thus greatly improved cartilage repair in rabbit full-thickness defects.In conclusion, this study demonstrated that 3D bioprinting of difunctional scaffolds could be a promising strategy for in situ AC regeneration based on aptamer-directed cell recruitment and growth-factor-enhanced cell chondrogenesis.

Biomaterials and Regenerative Medicine in Pain Management

“…For joint pain caused by articular cartilage and meniscus degeneration, hyaluronan scaffolds grafted with biomimetic brush-like nanofibrous polymers improved osteoarthritis within 8 weeks in a rat model by forming a lubrication layer on the cartilage surface [24]. Additionally, ECM scaffolds conjugated with aptamer HM69, viscoelastic PEGylated poly(glycerol sebacate) scaffolds combined with the osteoinductive mesoporous bioactive glass (MBG), and BMSC-laden biomimetic multiphasic scaffolds have shown to be effective in tissue regeneration [25][26][27]. Similarly, functionally graded scaffolds with anisotropy properties mimicking its hierarchical microstructure have shown superior repair outcomes in rotator cuff injury which often causes shoulder pain [28][29][30].…”

3D Bioprinted Implants for Cartilage Repair in Intervertebral Discs and Knee Menisci

“…In vivo, the complete construct had filled lesions on rabbit knee cartilage by week 12 post-implantation. Yang et al (2021) combined both GFs and MSC-recruiting aptamers in an interesting novel approach. Carbodiimide-mediated conjugation of HM69 aptamer was carried out on decellularized ECM, which was in turn dissolved in TGFβ3-containing GelMA.…”

Bioactive Inks Development for Osteochondral Tissue Engineering: A Mini-Review

“…In this regard, they concluded that growth factors addition to printable ink formulation positively affects cartilage tissue regeneration. Another study by a group of researchers exhibited that the addition of TGF-β3 to difunctional scaffold based on aptamer and decellularized cartilage ECM dispersed in GelMa promotes chondrogenic differentiation of BMSCs [ 52 ]. The improvement of full-thickness defect regeneration in rabbits’ cartilage demonstrated that the growth factor increment and aptamer could direct the cell, a promising strategy for in-situ cartilage regeneration.…”