Construction of a 3D-printed polycaprolactone scaffold functionalized with extracellular matrix and an MSC-affinity peptide for articular cartilage repair

Cartilage damage has emerged as a major clinical challenge due to the limited intrinsic regenerative capacity of articular cartilage. Current cartilage repair strategies often rely on exogenous cells and growth factors to promote tissue regeneration; however, their clinical translation is hindered by high costs, complex manufacturing processes, and potential immunogenicity. Thus, the development of high-performance acellular tissue-engineering scaffolds has attracted increasing attention. In this study, we engineered a biomimetic ternary composite scaffold consisting of polycaprolactone (PCL), a bone marrow mesenchymal stem cell (BMSC)-affinity peptide, and cartilage extracellular matrix (ECM) to facilitate efficient cartilage regeneration through synergistic multifunctional effects. PCL scaffolds with well-defined porous architectures and favorable mechanical properties were fabricated using three-dimensional (3D) printing. Following surface functionalization with the mesenchymal stem cell (MSC)-affinity peptide E7, the scaffolds were further coated with decellularized cartilage ECM. This biomimetic design enhances cell adhesion, selectively recruits endogenous MSCs, and provides the structural support required for tissue regeneration. Moreover, the bioactive components and biochemical cues retained within the ECM promote chondrogenic differentiation. In vitro studies demonstrated that E7-modified PCL (E7-PCL) significantly enhanced MSC adhesion and recruitment. The ECM/E7-modified composite scaffold further promoted stem-cell adhesion, proliferation, chondrogenic differentiation, and extracellular matrix deposition while maintaining excellent biocompatibility and mechanical integrity. In vivo, implantation of the ECM/E7-PCL (E/E7-P) scaffold resulted in markedly improved cartilage repair compared with ECM/PCL (E/P) scaffolds and untreated controls. Overall, these findings from in vitro and rabbit in vivo experiments indicate that E/E7-P represents a promising acellular tissue-engineering candidate for cartilage defect regeneration, pending further validation in more comprehensive experimental models.