Improving the Mechanical and Functional Performance of Extrusion-based Additive Manufactured Scaffolds for Bone Tissue Engineering

Abstract

Scaffold-based tissue engineering (TE) aims to aid in the repair and regeneration of bone defects. Bone defects due to high energy trauma, congenital malfunction and severe non-union fractures require a bone substitute for regeneration. At present, the demand of most commonly used bone substitute autogenous cancellous bone grafts far exceeds the supply. Moreover, it is not an ideal solution due to temporary disruption of donor site bone structure. Hence, the development of new synthetic bone substitutes or scaffolds that could be used instead of autogenous cancellous bone grafts has become a key priority in bone TE.

Scaffold acts as a platform to carry cells or therapeutic agents for regenerative therapies. An ideal scaffold is required to mimic the mechanical and biochemical properties of the native tissue. A scaffold should be mechanically robust with suitable architectural qualities to favour flow transport of nutrient for cell growth. It should also have osteoconductive properties to support cells through suitable surface chemistry. In this context high performance extrusion based additive manufactured scaffolds were developed for bone tissue engineering by improving their mechanical, biochemical and cell seeding efficiency.

Mechanical properties of the polymeric/ceramic scaffolds were improved by enhancing the interfacial interaction between the polymeric and ceramic phase through the use of coupling agents. Two different coupling agents, namely silane and POSS have been used in this research project. Both of the developed silanized poly (caprolactone)/tricalcium phosphate (PCL/TCP) and POSS modified PCL/TCP scaffolds have significantly improved mechanical properties and are suitable to use for cancellous bone tissue engineering. No detrimental effect of silane modification was found on cells. On the other hand POSS modified scaffolds showed better proliferative capability compared to control PCL/TCP scaffolds, which is due to the exposed TCP on the POSS modified PCL/TCP scaffolds.

To improve the proliferative and osteoconductive properties of the developed silanized PCL/TCP scaffolds, a thin layer of carbonated hydroxyapatite (CHA)-gelatin composite was coated onto the scaffolds by biomimetic co-precipitation process. In vitro studies showed promising results of the biomimetic composite coated scaffolds on proliferation and osteogenic differentiation of porcine bone marrow stromal cells. In vivo study was also conducted to evaluate the performance of biomimetic composite coated scaffolds.

To improve the functional performance of developed POSS modified PCL/TCP scaffolds by providing a cell entrapment system, a novel hierarchical scaffold that combines the advantageous properties of AM scaffold and porous foam scaffold was developed. In the hierarchical structure PCL/TCP(POSS)-foam scaffolds the macro-sized PCL/TCP(POSS) filaments provide mechanical support and the porous gelatin foam structure formed by freeze drying acts as a cell entrapment system. From the manufacturing point of view, to fabricate hierarchical scaffolds, our developed approach is considerably simpler than combining electrospinning with AM. In vitro results showed notably higher proliferative capability on PCL/TCP(POSS)-foam scaffolds compared to PCL/TCP(POSS) scaffolds.

In summary, it has been found that coupling agents improve mechanical properties of the polymer/ceramic scaffolds significantly. Scaffolds with improved mechanical properties can be further modified to enhance functional performance of the scaffolds. This study makes significant contribution in the field of extrusion based AM scaffolds by improving mechanical properties of the scaffolds by using coupling agents and functional performance of the scaffolds by developing thin biomimetic composite coating and hierarchical structure for cells entrapment system.