Advances in nanoenabled 3D matrices for cartilage repair

Cartilage repair strategies are evolving at a fast pace with technology development. Matrices that offer multifaceted functions and a full adaption to the cartilage defect are of pivotal interest. Current cartilage repair strategies face numerous challenges, mostly related to the development of highly biomimetic materials, non-invasive injectable solutions, and adequate degradation rates. These strategies often fail due to feeble mechanical properties, the inability to sustain cell adhesion, growth, and differentiation or by underestimating other players of cartilage degeneration, such as the installed pro-inflammatory microenvironment. The integration of nanomaterials (NMs) into 3D scaffolds, hydrogels and bioinks hold great potential in the improvement of key features of materials that are currently applied in cartilage tissue engineering. NMs offer a high surface to volume ratio and their multiple applications can be explored to enhance cartilage mechanical properties, biocompatibility, cell differentiation, inflammation modulation, infection prevention and even to function as diagnostic tools or as stimuli-responsive cues in these 3D structures. In this review, we have critically reviewed the latest advances in the development of nanoenabled 3D matrices - enhanced by means of NMs - in the context of cartilage regeneration. We have provided a wide perspective of the synergistic effect of combining 3D strategies with NMs, with emphasis on the benefits brought by NMs in achieving functional and enhanced therapeutic outcomes. STATEMENT OF SIGNIFICANCE: Cartilage is one of the most challenging tissues to treat owing to its limited self-regeneration potential. Novel strategies using nanoenabled 3D matrices have emerged from the need to design more efficient solutions for cartilage repair, that take into consideration its unique mechanical properties and can direct specific cell behaviours. Here we aim to provide a comprehensive review on the synergistic effects of 3D matrices nanoenrichment in the context of cartilage regeneration, with emphasis on the heightening brought by nanomaterials in achieving functional and enhanced therapeutic outcomes. We anticipate this review to provide a wide perspective on the past years' research on the field, demonstrating the great potential of these approaches in the treatment and diagnosis of cartilage-related disorders.