Effect of Icariin on Engineered 3D-Printed Porous Scaffolds for Cartilage Repair

Abstract

In recent times, cartilage defects have been the most common athletic injuries, often leading to dreadful consequences such as osteoarthritis, pain, joint deformities, and other symptoms. It is also evident that damage to articular cartilage is often difficult to recover or self-heal because of poor vascular, nervous, and lymphatic supplies. Moreover, cartilage cells have poor regeneration ability and high maturity. Inspired by these facts and the rapid advances in the field of tissue engineering (TE), we fabricated highly porous three-dimensional (3D) scaffold architectures based on cell-responsive polymeric inks, i.e., sodium alginate and gelatin (SA-Gel, 1:3 ratio), by a novel 3D printing method. Moreover, the effect of various processing parameters was systematically investigated. The printed scaffolds of polymer composites gels with excellent transparency, moderate viscosity, and excellent fluid properties showed good surface morphology, better thermal stability and swelling effect, and unique interconnected porous architectures at the optimized operating parameters. In vitro cell proliferation experiments of these cytocompatible scaffolds showed the excellent adhesion rate and growth behavior of chondrocytes. In addition, the porous architectures facilitated the efficient distribution of cells with only a few remaining on the surface, which was confirmed by confocal laser scanning microscopic (CLSM) observations. Icariin (ICA) addition at a concentration of 10 μg/mL further significantly enhanced the proliferation of chondrocytes. We envision that these cell-responsive polymeric inks in the presence of growth regulators like ICA may have potential in engineering complex tissue constructs toward diverse applications in TE.

Icariin-Functionalized Coating on TiO2 Nanotubes Surface to Improve Osteoblast Activity In Vitro and Osteogenesis Ability In Vivo

“…In addition, precious results also demonstrated that icariin could be conjugated with nanofiber hydrogel scaffolds to promote chondrogenic differentiation of bone marrow mesenchymal stem cells [23]. In summary, previous reports mostly focus on the usage of icariin in bone tissue-engineering scaffold or the cartilage [24] or osteochondral interface restoration [25]. However, polymer-scaffolding materials are not suitable for dental implants because of strength issues.…”

Herbal Remedies as Potential in Cartilage Tissue Engineering: An Overview of New Therapeutic Approaches and Strategies

“…Furthermore, in a chondrocyte alginate hydrogel 3D culture, icariin was able to increase proliferation, enhance chondrogenic marker expression, promote ECM synthesis, and markedly suppress catabolic gene expression including MMP-2, MMP-9, MMP-13, Adamts4, and Adamts5, possibly due to its role in activating HIF-1α [82]. Moreover, after transplantation into a mouse model, the icariin-loaded 3D hydrogel culture of chondrocyte alginate hydrogel significantly improved osteochondral defects and increased articular chondrocyte repair, as shown by higher histological scores [82]; additionally, in an in vitro study with a highly porous 3D scaffold based on sodium alginate and gelatin in 3D printing, icariin significantly promoted the proliferation of chondrocytes [79]. Additionally, in an in vivo study on the anterior cruciate ligament of the mouse in which a model of OA and a micro mass culture of mouse chondrocytes were induced, treatment with icariin resulted in an increased cartilage thickness; an upregulated expression of COL2A1; a reduced chondrocyte hypertrophy; a downregulated expression of collagen type X and MMP13; an upregulated expression of AGC, SOX9, and parathyroid hormone related proteins (PHrP); and a down-regulation of Indian hedgehog (Ihh) and genes regulated by Ihh [83][84][85].…”

Development of new biocompatible 3D printed graphene oxide-based scaffolds

“…On the other hand, various studies demonstrated that the 3D controlled scaffold architecture significantly affects its mechanical properties [30,31] as well as bone cell adhesion and proliferation [32,33]. Therefore, recent works focused on the development of 3D printed scaffolds [34][35][36] using different techniques, such as stereolithogaphy [37,38], 3D plotting [39], selective laser sintering [40], bioprinting [41], and fused deposition modelling (FDM) [42]. FDM is the most widely used additive manufacturing method and presents several advantages compared with other techniques [43].…”