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3D electrospun nanofibrous scaffolds have been developed for cartilage regeneration, however, there is no consensus on the preferable method for biocompatible scaffolds that enhance regeneration and attenuate inflammation. We designed a 3D porous electrospun polylactic acid (PLA) @gelatin-based scaffold by a novel method. Chondroitin sulfate (CS), commonly used in clinical cartilage treatment, is capable of regulating cartilage formation and inhibiting inflammation. Thus we further functionalized the 3D scaffold by crosslinking of CS, assuming that CS-functionalized scaffold (CSS) would promote cartilage regeneration and modulate inflammation. We confirmed that CSS exhibits not only appropriate reversible compressibility and mechanical property, but also appropriate biocompatibility, allowing cell proliferation. In vitro , the potential of CSS for chondrogenic differentiation was improved compared to control and PLA@gelatin scaffold as chondrogenic markers Collagen2 and Aggrecan was significantly increased. Meanwhile, significant reduction in two crucial inflammatory factors (NO and PGE2) in CSS group demonstrated inflammation inhibition. In vivo , rabbit cartilage defects were created and CSS effectively promoted cartilage repair. Additionally, superior anti-inflammation effect of CSS was demonstrated by reduction in iNOS and PGES, enzymes producing NO and PGE2, respectively by immunohistology. Our results indicated the preferable property of CSS for cartilage regeneration and its potential in immunoregulation. [ABSTRACT FROM AUTHOR]

• Cartilage decellularized matrix (CDM) is processed into inks for 3D printing. • CDM-based scaffolds with controlled 3D shape and pore structure are obtained. • Fibers can improve the mechanical property of 3D-printed CDM scaffolds. • 3D-printed fiber-reinforced CDM scaffolds exhibit elasticity in wet condition. • Fiber-reinforced CDM scaffolds can repair articular cartilage defects in rabbits. Cartilage decellularized matrix (CDM) is considered a promising biomaterial for fabricating cartilage tissue engineering scaffolds. An ideal CDM-based scaffold should possess customizable 3D shape for complex tissue regeneration and proper pore size for cell infiltration, as well as provide mechanical support for cell growth. 3D printing is an efficiently technique for preparing customizable 3D scaffolds, however, fabricating CDM-based 3D-printed scaffolds with customizable shapes, proper pore structure and satisfactory mechanical properties remains a challenge. In the current study, to achieve customizable CDM-based 3D scaffolds, CDM was successfully processed into inks suitable for 3D printing. Further, the poor mechanics of CDM-based scaffolds were significantly improved by adding electrospinning fiber into the CDM-based inks for 3D printing. Importantly, the 3D-printed electrospinning fiber-reinforced CDM-based scaffold presented good biocompatibility and can enhance repair articular cartilage defects in rabbits. The current study provides a novel strategy for printing electrospinning fiber-reinforced CDM-based scaffolds for tissue regeneration. [ABSTRACT FROM AUTHOR]

The fabrication of three-dimensional (3D) electrospun fibrous scaffolds with customizable shapes and large pores is a challenging task. In this study, for the first time, one-dimensional (1D) gelatin/poly (lactic- co -glycolic acid) (PLGA) electrospun fibers were processed into inks suitable for 3D printing. By combining 3D printing and freeze drying, electrospun fiber-based inks were successfully fabricated into 3D-printed scaffolds (3DP) with precisely controlled shapes and large pores, in addition to fibrous surface morphologies similar to that of a native extracellular matrix (ECM). The 3DP exhibited good elasticity and water-induced shape memory, and was found to be superior to 3D-printed scaffolds fabricated using pure gelatin fibers and freeze-shaped scaffolds fabricated using non-fibrous gelatin/PLGA powder. Moreover, 3DP combined with chondrocytes achieved satisfactory cartilage regeneration in vivo. The novel strategy of 3D printing electrospun fibers established in this study provides a research model for the design and fabrication of multiple scaffolds for various tissue regeneration applications. Unlabelled Image • Electrospun fibers were processed into three-dimensional inks for the first time. • Fiber scaffolds with controlled shapes and large pores were successfully fabricated. • Three-dimensional printed fiber scaffolds exhibited elastic property in the wet condition. • Three-dimensional fiber scaffolds combined with chondrocytes achieved satisfactory cartilage regeneration in vivo. [ABSTRACT FROM AUTHOR]

• Cartilage decellularized matrix was processed into hydrogel (CDEM-pHA). • CDEM-pHA was injectable and photo-crosslinkable. • CDEM-pHA combined with chondrocytes formed mature cartilage in vivo. Cartilage decellularized extracellular matrix (CDEM) is a promising biomaterial for preparing tissue engineering scaffolds, and CDEM-based hydrogels constitute an ideal choice for repairing cartilage damage. In this study, CDEM powders and photo-responsive hyaluronic acid (pHA) were successfully fabricated into injectable and photo-crosslinkable hydrogel (CDEM-pHA). The rheological properties of CDEM-pHA indicated that CDEM-pHA exhibited shear-thinning behavior, and the storage modulus of the hydrogel increased with increasing UV irradiation. Chondrocytes were loaded into CDEM-pHA and implanted into the subcutaneous tissue of nude mice for eight weeks; the results indicated that CDEM-pHA combined with chondrocytes successfully regenerated mature cartilage in vivo. This study established a novel strategy for preparing CDEM-based hydrogel for cartilage regeneration. [ABSTRACT FROM AUTHOR]

Decellularized allogeneic and xenogeneic articular cartilage matrix scaffolds (CMS) are considered ideal scaffolds for cartilage regeneration owing to their heterogeneous architecture, and biochemical and biomechanical properties of native articular cartilage. However, the dense structure of the articular cartilage extracellular matrix, particularly the arrangement of collagen fibers, limits cellular infiltration, leading to poor cartilage regeneration. In addition, the incomplete removal of xenograft cells is associated with immunogenic reaction in the host. To facilitate the migration of chondrocytes into scaffolds and the rate of decellularization processing, we applied a carbon dioxide laser technique to modify the surface of porcine CMS while retaining major properties of the scaffold. By optimizing the laser parameters, we introduced orderly, lattice-arranged conical micropores of suitable depth and diameter onto the cartilage scaffold surface without affecting the cartilage shape or mechanical properties. We found that laser-modified CMS (LM-CMS) could enhance the degree of decellularization and were conducive to cell adhesion, as compared with the intact CMS. Decellularized scaffolds were seeded with rabbit-derived chondrocytes and cultured for 8 weeks in vitro. We found that cell-scaffold constructs formed cartilage-like tissue within the micropores and on the scaffold surface. In vivo, we found that cell-scaffold constructs subcutaneously implanted into the flanks of nude mice formed ivory-white neocartilage with high contents of DNA and cartilage matrix components, as well as good mechanical strength as compared with native CMS. Furthermore, scaffolds combined with autogenous chondrocytes induced neocartilage and better structural restoration at 8 weeks after transplantation into rabbit knee articular cartilage defects. In conclusion, decellularized xenogeneic CMS with laser-machined micropores offers an ideal scaffold with high fidelity for the functional reconstruction of articular cartilage. • Cartilage specific scaffold LM-DCMS with high porosity were fabricated by using laser technique and decellularization. • LM-DCMS could improve cell adhesion by increasing contact area and providing rough surface within micropores. • LM-DCMS were showed excellent cartilage regeneration ability in vitro and in vivo. • LM-DCMS seeded with autologous chondrocytes could successfully repair xenogeneic cartilage defects in a rabbit model. [ABSTRACT FROM AUTHOR]