Perspectives on Synthetic Materials to Guide Tissue Regeneration for Osteochondral Defect Repair

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.

Human Salivary Histatin-1-Functionalized Gelatin Methacrylate Hydrogels Promote the Regeneration of Cartilage and Subchondral Bone in Temporomandibular Joints

“…Scaffold material is an indispensable element for TE to facilitate cell migration, proliferation, and differentiation as well as the slow release of bioactive agents [ 15 ]. In recent TE techniques, there is a trend in the design of material scaffolds to contain three parts with different physicochemical and biological properties in order to facilitate the regeneration of bone, cartilage, and the osteochondral interface separately [ 36 ]. However, such complicated designs are less favorable for their industrial fabrication and clinical application.…”

Challenges and Innovations in Osteochondral Regeneration: Insights from Biology and Inputs from Bioengineering toward the Optimization of Tissue Engineering Strategies

“…This interface has been approached in scaffolds through additional layers or phases with different materials and properties. In scaffolds, these phases (between bone and cartilage) have been treated with various porosities [ 60 , 61 , 62 ], modulus [ 63 , 64 , 65 , 66 ], and compositions with materials [ 67 , 68 ] to create the transition between cartilage and subchondral bone [ 69 ].…”

“…Several designs of scaffolds using synthetic materials have been approached. Given the morphological characteristics in cellular behavior [ 69 , 70 , 71 , 72 , 73 , 74 ], scaffolds with controlled morphology and chemic should improve osteochondral regeneration, in combination with materials whose properties are known as instructive beings. Accordingly, as demonstrated in Table 1 , several types of biocompatible materials have been used to build scaffolds for the osteochondral tissue, including natural polymers, synthetic polymers, metallic polymers, and inorganic polymers [ 75 ].…”

“…Recently, scaffolds for osteochondral regeneration have used three main types of 3D printing, including SLA, FFF, and SLS [ 69 , 127 ]. Studies have shown that scaffolds with uniform pores for cartilaginous and subchondral regeneration, printed in 3D, with the junction of MSCs demonstrated a chondrogenic and osteogenic differentiation to osteochondral structures [ 128 , 129 , 130 ].…”

“…As already mentioned, it is important to develop a biomimetic scaffold to imitate the gradient of cartilage, calcified cartilage, and bone. Two categories of scaffolds have been developed: biphasic and tri/multiphase [ 69 , 75 ]. Biphasic scaffolds for osteochondral regeneration can be joined by a bone scaffold with a cartilage scaffold [ 75 ].…”