Calcium Phosphate–Collagen Scaffold with Aligned Pore Channels for Enhanced Osteochondral Regeneration

Abstract

This study reports the development of a bilayered scaffold with aligned channels produced via a sequential coextrusion and unidirectional freezing process to facilitate upward bone-marrow stem-cell migration. The biomimetic scaffold with collagen and biphasic calcium phosphate (BCP) layers is successfully fabricated with matching of the cartilage and bone layers. The aligned structure results in an enhancement of the compressive strength, and the channels enable tight anchoring of the collagen layers on the BCP scaffolds compared with a randomly structured porous scaffold. An in vitro evaluation demonstrates that the aligned channels guide the cells to attach on the surface in highly stretched shapes and migrate upward faster than the random structure. In addition, in vivo assessment reveals that the aligned channels yield superior osteochondral tissue regeneration compared with the random structure. Moreover, the channel diameter greatly affects the tissue regeneration, and the scaffold with a channel diameter of ≈270 µm exhibits the optimal regeneration because of sufficient nutrient supply and adequate tissue ingrowth. These findings indicate that the introduction of aligned channels to a bilayered scaffold provides an effective approach for osteochondral tissue regeneration.

Anisotropic mineralized collagen scaffolds accelerate osteogenic response in a glycosaminoglycan-dependent fashion

“…Of note, another study by Seong et al indicated that small channels enhanced proliferation and migration in vitro and pore sizes of 270 mm were best for cell migration in vivo. 62 This could explain the lack of migration and metabolic activity differences in our scaffolds, which had average pore diameters in the range of 150-200 mm.…”

Anisotropic mineralized collagen scaffolds accelerate osteogenic response in a glycosaminoglycan-dependent fashion

“…This difference in results could be attributed to a difference in metabolic activity of PCL structures; however, our scaffolds had no metabolic activity differences, indicating no bias on ALP activity. Of note, another study by Seong et al indicated that small channels enhanced proliferation and migration in vitro and pore sizes of 270μm were best for cell migration in vivo 62 . This could explain the lack of migration and metabolic activity differences in our scaffolds, which had average pore diameters in the range of 150 -200 μm.…”

Therapeutic Potential of Articular Cartilage Regeneration using Tissue Engineering Based on Multiphase Designs

“…Yun-Jeong et al have shown that not only the microenvironment generated by the composition of the biomaterials impact on a better imitation of the osteochondral unit, but also the scaffolding structure has an important influence, being an aligned structure the most adequate in comparison with a randomly structured scaffold [55]. A stratified design of aligned channels in a biphasic scaffold using collagen type I and biphasic calcium phosphate (BCP) to mimic the cartilage and bone tissue, respectively, was manufactured by using an exquisite unidirectional freeze-casting process.…”

“…Likewise, BCP provides significant osteoconductivity, bioactivity, and mechanical features [54]. However, privileging on the composition, the generation of a biphasic scaffold with a longitudinal roughness of the inner channels that serves as a guide for the correct adhesion of the cells; it results in a topography that truly emulates the osteochondral unit and shows in vivo a superior regeneration of the osteochondral tissue compared to the random structure [55].…”