Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds

Abstract

The osteochondral interface of an arthritic joint is notoriously difficult to regenerate due to its extremely poor regenerative capacity and complex stratified architecture. Native osteochondral tissue extracellular matrix is composed of numerous nanoscale organic and inorganic constituents. Although various tissue engineering strategies exist in addressing osteochondral defects, limitations persist with regards to tissue scaffolding which exhibit biomimetic cues at the nano to micro scale. In an effort to address this, the current work focused on 3D printing biomimetic nanocomposite scaffolds for improved osteochondral tissue regeneration. For this purpose, two biologically-inspired nanomaterials have been synthesized consisting of (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lactic-co-glycolic) acid (PLGA) nanospheres encapsulated with chondrogenic transforming growth-factor β1 (TGF-β1) for sustained delivery. Then, a novel table-top stereolithography 3D printer and the nano-ink (i.e., nHA + nanosphere + hydrogel) were employed to fabricate a porous and highly interconnected osteochondral scaffold with hierarchical nano-to-micro structure and spatiotemporal bioactive factor gradients. Our results showed that human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation were greatly improved in the biomimetic graded 3D printed osteochondral construct in vitro. The current work served to illustrate the efficacy of the nano-ink and current 3D printing technology for efficient fabrication of a novel nanocomposite hydrogel scaffold. In addition, tissue-specific growth factors illustrated a synergistic effect leading to increased cell adhesion and directed stem cell differentiation.

Current advances in solid free-form techniques for osteochondral tissue engineering

“…Reprinted with permission from Ref. [19] revealed good mechanical properties and thermal stabilities; moreover, cytotoxicity tests confirmed their biocompatibility with no cytotoxic effect on cells metabolism. In addition, two different treatments have been proposed, using fetal bovine serum (FBS) and methanol (MeOH).…”

“…This work revealed good outcomes and the authors concluded that subchondral bone migration is related with cartilage regeneration in critical size osteochondral defects. In a different and more advanced approach, Castro et al [19] developed two biologically inspired nanomaterials: (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lacticco-glycolic) acid (PLGA) nanospheres encapsulated with the transforming growth-factor β1 (TGF-β1). The authors used a novel table-top SL 3D printer to fabricate a hierarchical scaffold with the aim to provide biological cues at nano-and microscales (Fig.…”

3D printing of hydrogel composite systems: Recent advances in technology for tissue engineering

“…Improved mechanical properties and biological properties Cartilage [91] Fiber 3D plotting Acrylamide Cellulose short fibril Anisotropic swelling behaviors 4D printing [92] 3D plotting Alginate PLA continuous nanofiber Improved mechanical properties and biological properties Cartilage [93] Casting + 3D plotting PEGDGE, Acrylamide PU continuous microfiber Improved mechanical properties General [94] 3D plotting Alginate, Acrylamide Emax (UV-curable epoxy)…”

Simulated Body Fluid Nucleation of Three-Dimensional Printed Elastomeric Scaffolds for Enhanced Osteogenesis

“…It is well known that surface topography play a critical role in enhancing cell adhesion as our previous work has illustrated. [22][23][24][25] Increased surface roughness and altered surface chemistry produces scaffolds with increased surface area and bioactivity for protein adsorption and subsequent cell adhesion. In addition to increased cell adhesions, hFOB proliferation (Fig.…”

“…Therefore, this study is the first to illustrate the great potential of 3D printed Gel-lay scaffolds with SBF nucleation for osseous tissue repair. 24,72, and 120 h nucleation times. The nucleated scaffolds were then removed, blotted dry, and air-dried.…”