No abstract

Regenerative engineering holds the potential to treat clinically pervasive osteochondral defects (OCDs). In a synthetic materials-guided approach, the scaffold’s chemical and physical properties alone instruct cellular behavior in order to effect regeneration, referred to herein as “instructive” properties. While this alleviates the costs and off-target risks associated with exogenous growth factors, the scaffold must be potently instructive to achieve tissue growth. Moreover, toward achieving functionality, such a scaffold should also recapitulate the spatial complexity of the osteochondral tissues. Thus, in addition to the regeneration of the articular cartilage and underlying cancellous bone, the complex osteochondral interface, composed of calcified cartilage and subchondral bone, should also be restored. In this Perspective, we highlight recent synthetic-based, instructive osteochondral scaffolds that have leveraged new material chemistries as well as innovative fabrication strategies. In particular, scaffolds with spatially complex chemical and morphological features have been prepared with electrospinning, solvent-casting–particulate-leaching, freeze-drying, and additive manufacturing. While few synthetic scaffolds have advanced to clinical studies to treat OCDs, these recent efforts point to the promising use of the chemical and physical properties of synthetic materials for regeneration of osteochondral tissues.

In a material-guided approach, instructive scaffolds that leverage potent chemistries may efficiently promote bone regeneration. A siloxane macromer has been previously shown to impart osteoinductivity and bioactivity when included in poly­(ethylene glycol) diacrylate (PEG-DA) hydrogel scaffolds. Herein, phosphonated-siloxane macromers were evaluated for enhancing the osteogenic potential of siloxane-containing PEG-DA scaffolds. Two macromers were prepared with different phosphonate pendant group concentrations, poly­(diethyl­(2-(propylthio)­ethyl)­phosphonate methylsiloxane) diacrylate (PPMS-DA) and 25%-phosphonated analogue (PPMS-DA 25%). Macroporous, templated scaffolds were prepared by cross-linking these macromers with PEG-DA at varying mol % (15:85, 30:70, and 45:55 PPMS-DA to PEG-DA; 30:70 PPMS-DA 25% to PEG-DA). Other scaffolds were also prepared by combining PEG-DA with PDMS-MA (i.e., no phosphonate) or with vinyl phosphonate (i.e., no siloxane). Scaffold material properties were thoroughly assessed, including pore morphology, hydrophobicity, swelling, modulus, and bioactivity. Scaffolds were cultured with human bone marrow-derived mesenchymal stem cells (normal media) and calcium deposition and protein expression were assessed at 14 and 28 days.

Scaffolds that recapitulate the spatial complexity of orthopedic interfacial tissues are essential to their regeneration. This requires a method to readily and flexibly produce scaffolds with spatial control over physical and chemical properties, without resulting in hard interfaces. Herein, we produced hydrogel scaffolds with spatially tunable arrangements and chemistries (SSTACs). Using solvent-induced phase separation/fused salt templating (SIPS/salt), scaffold elements are initially prepared with a tunable pore size and with one or more UV-reactive macromers. After trimming to the desired dimensions, these are physically configured and fused together to form the SSTACs. Using this method, three SSTAC designs were prepared, including one that mimicked the osteochondral interface. Bright-field/fluorescent microscopy revealed spatial control of pore size and chemical composition across a relatively smooth and integrated interface, regardless of layer composition. An interface formed by a SSTAC was determined to withstand a similar shear force to an analogous scaffold with no interface.