Tissue engineering of bone and cartilage has progressed from simple to sophisticated materials with defined porosity, surface features, and the ability to deliver biological factors. To avoid eliciting a foreign body response due to inclusion of allogeneic cells, advances in functional scaffold design harness the endogenous ability of the body to regenerate. We review advancements in the surface and structural properties of typical polymeric, ceramic, and metallic scaffolds for orthopedic use. First, we provide an overview of methods and materials, with a focus on additive manufacturing and electrospinning. Multidimensional physical properties of scaffolds, including three-dimensional macrostructure, pore design, and two-dimensional hierarchical surface roughness, allow tissue regeneration at different spatial and temporal scales. Enhanced biological response can be achieved through surface functionalization and the use of exogenous factors. Finally, different in vitro and in vivo models are discussed for translation of these technologies for clinical use.

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Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.