Combining multi-scale 3D printing technologies to engineer reinforced hydrogel-ceramic interfaces.

Tissue interfaces in musculoskeletal systems are complex structures requiring precise mechanical and biological integration. Prior research has shown that single-material scaffolds often fail to replicate the mechanical and structural diversity of native tissues. This gap motivated the development of multi-material constructs that mimic natural tissue interfaces. Established knowledge includes the use of hydrogels for cartilage and bioceramics for bone, but integration remains a challenge. No prior work had resolved how to effectively combine these materials at multiple scales. The need for a mechanically stable interface in osteochondral defects has driven innovation in 3D printing technologies. Microscale organization of fibres is known to influence tissue function, but its application in composite scaffolds is limited. The challenge lies in preserving micro-architecture during multi-material printing. This paper introduces a novel approach to address these limitations.

This study aimed to develop a composite osteochondral plug using multi-scale 3D printing technologies. The specific problem addressed is the lack of mechanically stable interfaces between bone and cartilage in tissue engineering. The motivation stems from the need for constructs that can withstand surgical handling and provide structural support in osteochondral defects. The authors propose integrating extrusion printing and melt electrowriting to achieve this. A key objective was to engineer a reinforced interface between a ceramic bone support and a hydrogel cartilage compartment. The study sought to evaluate mechanical reinforcement and biological functionality of the composite plug. The approach was designed to preserve micro-architecture while enabling spatial organization of fibres. The ultimate goal was to create a construct suitable for regenerative applications in musculoskeletal tissues.

The researchers combined extrusion printing and melt electrowriting to fabricate a composite osteochondral plug. A bioceramic ink composed of α-tricalcium phosphate, nanohydroxyapatite, and a poloxamer was extrusion printed as a bone support. Melt electrowriting was used to create spatially organized polycaprolactone microfibres as a cartilage compartment. The mild setting reaction of the ceramic ink allowed printing within the microfibrous mesh. The ceramic-integrated mesh extended into the hydrogel region of the plug. Gelatin-based hydrogels, loaded with chondroprogenitor cells, were embedded around the mesh. The interlocking design was tested for adhesion strength using mechanical assays. The composite construct was evaluated for structural stability during handling and ex vivo implantation.

The interlocking design increased hydrogel-to-ceramic adhesion strength by more than 6.5-fold compared to non-interlocking structures. The MEW mesh provided compressive reinforcement in the chondral compartment, reaching 20-fold improvement over pristine hydrogels. The ceramic bone support demonstrated osteogenic potential in vitro. The cartilage compartment supported matrix deposition by chondroprogenitor cells. The neo-synthesized cartilage matrix further reinforced the interface. The composite plug retained structural stability during handling and ex vivo implantation. The osteal compartment showed evidence of bone formation in vitro. The chondral compartment exhibited compressive properties similar to native cartilage.

The authors propose that the multi-material, multi-scale 3D printing approach offers a promising strategy for engineering composite constructs. The interlocking design enhances adhesion strength at the bone-to-cartilage interface. The MEW mesh contributes to mechanical reinforcement in the cartilage compartment. The ceramic ink supports osteogenesis in vitro. The hydrogel compartment facilitates cartilage matrix deposition. The composite plug maintains structural integrity during handling and implantation. The study suggests that this approach could be applied to musculoskeletal and connective tissue interfaces. The findings support the potential of multi-scale printing in regenerative medicine.