Development of Novel Three-Dimensional Printed Scaffolds for Osteochondral Regeneration

Abstract

As modern medicine advances, various methodologies are being explored and developed in order to treat severe osteochondral defects in joints. However, it is still very challenging to cure the osteochondral defects due to their poor inherent regenerative capacity, complex stratified architecture, and disparate biomechanical properties. The objective of this study is to create novel three-dimensional (3D) printed osteochondral scaffolds with both excellent interfacial mechanical properties and biocompatibility for facilitating human bone marrow mesenchymal stem cell (MSC) growth and chondrogenic differentiation. For this purpose, we designed and 3D printed a series of innovative bi-phasic 3D models that mimic the osteochondral region of articulate joints. Our mechanical testing results showed that our bi-phasic scaffolds with key structures have enhanced mechanical characteristics in compression (a maximum Young's modulus of 31 MPa) and shear (a maximum fracture strength of 5768 N/mm 2 ) when compared with homogenous designs. These results are also correlated with numerical simulation. In order to improve their biocompatibility, the scaffolds' surfaces were further modified with acetylated collagen (one of the main components in osteochondral extracellular matrix). MSC proliferation results demonstrated that incorporation of a collagen, along with biomimetically designed micro-features, can greatly enhance MSC growth after 5 days in vitro. Two weeks' chondrogenic differentiation results showed that our novel scaffolds (dubbed ''key'' scaffolds), both with and without surface collagen modification, displayed enhanced chondrogenesis (e.g., 130%, 114%, and 236% increases in glycosaminoglycan, type II collagen deposition, and total protein content on collagen-modified key scaffolds when compared with homogeneous controls).

A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair

“…nHA was first synthesized using a wet chemistry procedure and a hydrothermal process, as thoroughly described in our previous studies [38, 39]. Then, nHA particles were conjugated onto scaffolds using a process described by Aishwarya et al [40] and our previous study [41]. First, PLA scaffolds were aminolysed.…”

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

“…After 10 weeks, the regenerated femoral heads presented smooth, continuous and homogeneous articular cartilage layer and a good subchondral bone integration. Recently, Holmes et al [29] created novel osteochondral scaffolds with both excellent interfacial mechanical properties and biocompatibility for facilitating human bone marrow mesenchymal stem cell (MSC) growth and chondrogenic differentiation. In this sense, the authors designed and printed a series of innovative biphasic 3D models that mimic the osteochondral region of articulate joints.…”

Cartilage-Bone Interface Features, Scaffold and Cell Options for Regeneration

“…Specific differentiation of these cells into proper lineages is achieved by incorporating relevant biomolecules into scaffolds in a specially controlled manner. For example, transforming growth factor beta1 (TGF-beta1) and transforming growth factor beta3 (TGF-beta3) are known to trigger these cells to differentiate into chondrogenic lineage, while bone morphogenic protein 2 (BMP2) can lead to osteogenic differentiaon [26][27][28][29]. Therefore, incorporating TGF-beta1 or TGF-beta3 into one side and BMP2 into the other, also coupled with the stem cells may form appropriate conditions to generate structures resembling the osteochondral interface.…”