Cell-free 3D wet-electrospun PCL/silk fibroin/Sr2+ scaffold promotes successful total meniscus regeneration in a rabbit model

Abstract

Considering the intrinsic poor self-healing capacity of meniscus, tissue engineering has become a new direction for the treatment of meniscus lesions. However, disturbed by mechanical stability and biocompatibility, most meniscus implants fail to relieve symptoms and prevent the development of osteoarthritis. The goal of this study was to develop a potential meniscal substitute for clinical application. Here, silk fibroin with good mechanical performance and biocompatibility, and strontium ion acting as bioactive factor, were incorporated with Ɛ-Polycaprolactone to fabricate a meniscus scaffold (SP-Sr). By the wet-electrospun method, the 3D SP-Sr provided suitable pore size (100–200 μm) and enough mechanical support (61.6 ± 2.9 MPa for tensile modulus and 0.11 ± 0.03 MPa for compressive modulus). Moreover, after addition of Sr2+, the SP-Sr seeded by rabbit adipose tissue-derived stromal cells (rADSCs) showed the highest secretion with 2.61- and 2.98-fold increase in collagen and aggrecan, respectively, compared with SF/PCL group. And the extracellular matrix related genes expression in SP-Sr also showed upregulation results. Particularly, the expression of the collagen II gene, which played a crucial role in the formation of meniscal inner avascular region, showed a 9-fold increase in SP-Sr compared with pure PCL group. Furthermore, the MRI results of SP-Sr implanted in rabbits with total meniscectomy for 6 months demonstrated effective prevention of meniscus extrusion and relieving joint space narrowing compared with meniscectomy group. And the effects of cartilage protection and delaying osteoarthritis development were confirmed by Pathological examination. Especially, after 6-month implantation, the neo-menisci showed similar structural constituent and mechanical performance. Statement of significanceMeniscus regeneration faces great challenge due to the meniscus having limited healing potential owing to its anisotropic structure, its hypocellularity and hypovascularity. The present tissue engineering solutions have failed to maintain the biological function for meniscus reconstruction in vivo because of fragile and poor biocompatible materials, leading to long-term joint degeneration. The goal of this study was to develop a meniscal substitute potential for clinical application. Here, silk fibroin and strontium were incorporated with Ɛ-Polycaprolactone by wet-electrospinning method to fabricate a meniscus scaffold (SP-Sr). The 6-month implantation results revealed that SP-Sr scaffold was effective in preventing meniscus extrusion, cartilage protection and delaying osteoarthritis development, and the regenerated menisci showed similar structural constituent and mechanical performance.