3D printed polycaprolactone/phosphoester-modified poly(amino acid)–graphene oxide scaffold for meniscal regeneration

Given the limited blood supply that results in the poor self-healing ability of the meniscus, use of meniscal tissue engineering (MTE) scaffolds has emerged as an effective strategy for the treatment of meniscal injuries. However, the efficacy of mesenchymal stem cells (MSCs) is limited in the inflammatory state caused by chronic injuries, making it challenging for existing meniscal implants to promote meniscal regeneration and delay articular cartilage degeneration in an inflammatory environment. This study introduces a method to incorporate phosphoester (PE) units into the main chain of poly(amino acids) (PAAs) through ring-opening copolymerization, subsequently creating a copolymer with graphene oxide (GO) to yield phosphoester-modified poly(amino acid)-graphene oxide (P-P-GO). PCL/P-P-GO scaffolds were fabricated by blending P-P-GO with polycaprolactone (PCL) and employing 3D printing technology. The PAAs of P-P-GO scaffolds provide a nutritious environment essential for MSC proliferation, migration, and differentiation, while the PE enhances the cell adhesion properties, with further improvements by GO. <i>In vitro</i> experiments have shown that the PCL/P-P-GO scaffolds upregulate the expression of chondrogenic-specific genes and increase the production of collagen and glycosaminoglycans. Additionally, γ-aminobutyric acid of the scaffolds can suppress the secretion of inflammatory factors, induce M2 polarization of macrophages, and promote angiogenesis. <i>In vivo</i> studies using a rabbit meniscectomy model have demonstrated that PCL/P-P-GO scaffolds can promote meniscal tissue regeneration and delay cartilage degeneration. After six months of implantation, the regenerated meniscus exhibited a structure and composition resembling natural meniscus, and the progression of osteoarthritis was significantly slowed. Compared to the traditional cell-loaded scaffold, PCL/P-P-GO scaffolds are easy to produce and cost-effective and hold broad translational potential for the clinical treatment of meniscal injuries.