3D-Printed Scaffolds Accelerate Cartilage Defect Repair

Recently, a research team led by Jung-Hwan Lee, Hye Sung Kim, and Hae-Won Kim from the Institute of Tissue Regeneration Engineering at Dankook University published a paper in Advanced Healthcare Materials titled “Strontium/Silicon/Calcium-Releasing Hierarchically Structured 3D-Printed Scaffolds Accelerate Osteochondral Defect Repair.”

The study developed a scaffold-mediated therapeutic ion delivery system, in which the scaffolds were fabricated from poly(ε-caprolactone) (PCL) and strontium (Sr)-doped bioactive nanoglass (SrBGn). The resulting scaffolds exhibited a unique hierarchical architecture characterized by 3D-printed macropores, micropores, and nanotopographical features arising from the integration of SrBGn, enabling enhanced osteochondral tissue regeneration.

Original article： https://onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.202400154

Research Overview

Articular cartilage defects represent a global clinical challenge, often leading to severe disability. Repairing large defects remains difficult, as they typically exceed the intrinsic self-healing capacity of cartilage and disrupt the underlying bone structure. To address this issue, the researchers developed a scaffold-mediated therapeutic ion delivery system.

The scaffolds were fabricated from poly(ε-caprolactone) (PCL) and strontium (Sr)-doped bioactive nanoglass (SrBGn), resulting in a hierarchically structured architecture characterized by 3D-printed macropores, micropores, and nanotopographical features arising from the integration of SrBGn. The SrBGn-μCh scaffolds are capable of releasing Sr, Si, and Ca ions, which collectively enhance chondrocyte activation, adhesion, proliferation, and the expression of chondrogenic maturation-related genes. This multi-ionic release significantly modulates chondrocyte metabolism and maturation, with Sr ions likely contributing to chondrocyte regulation via the Notch signaling pathway.

The structural and topographical cues of the scaffold further promote the recruitment, adhesion, spreading, and proliferation of both chondrocytes and bone marrow–derived mesenchymal stem cells (BMSCs). Meanwhile, Si and Ca ions facilitate osteogenic differentiation and angiogenesis, whereas Sr ions support the polarization of M2 macrophages, creating a regenerative microenvironment.

Overall, the results demonstrate that the SrBGn-μCh scaffolds accelerate osteochondral defect repair by delivering multiple therapeutic ions while providing biophysical and topographical guidance, ultimately supporting host cell function and tissue regeneration. This approach holds great promise for future osteochondral repair applications.

Figure 1. Fabrication and characterization of hierarchically structured 3D-printed scaffolds incorporating strontium-doped bioactive nanoglass (SrBGn) composites.


Figure 2. Enhanced in vitro chondrocyte activity mediated by multi-ionic release from SrBGn–μCh composite scaffolds.


Figure 3. Strontium ions released from SrBGn–μCh scaffolds modulate chondrocyte transcriptomic profiles, contributing to cartilage repair. Chondrocytes were cultured for 7 days with extracts from μCh, BGn–μCh, and SrBGn–μCh, followed by bulk RNA sequencing analysis. (BGn: BGn–μCh; SrBGn: SrBGn–μCh).


Figure 4. In addition to the combined effects of multiple ions, the nanotopographical cues of SrBGn further enhance chondrocyte adhesion


Figure 5. Composite scaffolds promote BMSC proliferation, migration, and osteogenic differentiation. (a–f) Indirect culture and (g–i) direct culture with the scaffolds.
 

Figure 6. SrBGn–μCh scaffolds promote cartilage and bone regeneration in an osteochondral defect model. (a–d) Assessment of wrist joint repair.


Figure 7. Progress in osteochondral defect repair using SrBGn–μCh scaffolds. The SrBGn–μCh scaffolds possess unique chemical and physical properties that collectively influence a series of cellular processes involved in osteochondral regeneration. The nanotopographical features conferred by the bioactive nanoglass within the scaffold play a key role in enhancing adhesion, spreading, and subsequent proliferation of both chondrocytes and BMSCs. In addition, the collective release of Sr²⁺, Si⁴⁺, and Ca²⁺ ions from the composite scaffolds accelerates chondrocyte maturation. Notably, Sr ions exert a unique effect by modulating chondrocyte and BMSC migration and promoting M2 macrophage polarization, whereas Si and Ca ions predominantly enhance BMSC osteogenic differentiation and angiogenesis. Through its hierarchical structure and morphological features, SrBGn–μCh effectively coordinates these host cell–mediated biological processes. During osteochondral defect regeneration, the synergistic interaction of multiple ions further strengthens this coordination.

Conclusion
In this study, 3D-printed SrBGn–μCh scaffolds were developed that significantly enhance osteochondral repair. Their unique hierarchical structure, combining macro-/micropores and nanotopographical cues, enables sustained multi-ion release of Sr, Si, and Ca, which positively influences the expression of genes associated with chondrocyte function and maturation, with Sr ions modulating the Notch signaling pathway. Furthermore, the nanotopographical features imparted by the integration of bioactive nanoglass synergistically accelerate adhesion, spreading, and subsequent proliferation of both chondrocytes and BMSCs. While Si and Ca ions predominantly enhance BMSC osteogenic differentiation and angiogenesis, Sr ions are particularly effective in promoting host cell recruitment and M2 macrophage polarization. These findings demonstrate that the SrBGn–μCh scaffolds hold great potential for future osteochondral repair applications.

Printing Example

The image above shows biological scaffolds 3D-printed using bioactive glass and bioceramics via photopolymerization DLP. These scaffolds provide researchers with a more efficient tool for conducting scientific studies.