Preparation of high precision multilayer scaffolds based on Melt Electro-Writing to repair cartilage injury

Abstract

Rationale: Articular cartilage injury is quite common. However, post-injury cartilage repair is challenging and often requires medical intervention, which can be aided by 3D printed tissue engineering scaffolds. Specifically, the high accuracy of Melt Electro-Writing (MEW) technology facilitates the printing of scaffolds that imitate the structure and composition of natural cartilage to promote repair. Methods: MEW and Inkjet printing technology was employed to manufacture a composite scaffold that was then implanted into a cartilage injury site through microfracture surgery. While printing polycaprolactone (PCL) or PCL/hydroxyapatite (HA) scaffolds, cytokine-containing microspheres were sprayed alternately to form multiple layers containing transforming growth factor-β1 and bone morphogenetic protein-7 (surface layer), insulin-like growth factor-1 (middle layer), and HA (deep layer). Results: The composite biological scaffold was conducive to adhesion, proliferation, and differentiation of mesenchymal stem cells recruited from the bone marrow and blood. Meanwhile, the environmental differences between the scaffold's layers contributed to the regional heterogeneity of chondrocytes and secreted proteins to promote functional cartilage regeneration. The biological effect of the composite scaffold was validated both in vitro and in vivo . Conclusion: A cartilage repair scaffold was established with high precision as well as promising mechanical and biological properties. This scaffold can promote the repair of cartilage injury by using, and inducing the differentiation and expression of, autologous bone marrow mesenchymal stem cells.

Melt Electrowriting of Scaffolds with a Porosity Gradient to Mimic the Matrix Structure of the Human Trabecular Meshwork

“…20 μm fiber diameter, 200 μm interfiber spacing and 1 mm height, compression moduli of ca. 14 kPa [55] or slightly below 1 MPa [39] were reported.…”

“…Scaffolds with pore size 100 to 400 µm and fiber diameter of ca. 10 µm were used for cartilage regeneration [39, 40]. MEW has been used for skin [41], cardiac [33, 36], and ligament tissue engineering [35], and biomimetic designs of tympanic membrane [42] and cartilage [39, 40].…”

Osteochondral Tissue Engineering: The Potential of Electrospinning and Additive Manufacturing

“…Of note, whipping instability during electrospinning is critical for further fibre elongation and solvent evaporation, meaning that its suppression often results in fibres with larger diameters [ 352 ]. Nevertheless, recent studies have proven the potential of electrohydrodynamic direct writing techniques in the field of cartilage/osteochondralTE [ 353 , 354 ].…”

Review on Computer-Aided Design and Manufacturing of Drug Delivery Scaffolds for Cell Guidance and Tissue Regeneration

“…For example, a collagen type 1 solution containing PLGA microspheres loaded with VEGF, BMP-2, or FGF-2 was incorporated into the pores of polycaprolactone fumarate scaffolds and crosslinked under UV light to stimulate vascular ingrowth and tissue regeneration ( Wagner et al, 2018 ). Growth factor-loaded microspheres were also deposited on the surface of melt electrowriting scaffold pores by an inkjet spray drying technique to prepare three layers of scaffolds for repairing cartilage injury ( Han et al, 2020 ). The scaffold consisted of a surface layer loaded with BMP-7 and TGF-β1, a middle layer loaded with IGF-1 and TGF-β1, and a deep layer loaded with hydroxyapatite (HA) and TGF-β1.…”