Shape memory polymer foams as bone scaffolds for bone regeneration

Abstract

Shape memory polymer (SMP) foam, which is a type of smart material, can undergo a shape transition in response to a specific external stimulus. Although it has been remarkable studied for their potential in bone regeneration, great efforts are still being made in scaffold design for improvement. In particularly, SMP foam with sufficient mechanical properties and biocompatibility for load-bearing bone defects. Therefore, for the sake of successful application of SMPs in scaffold-assisted bone regeneration, the material design and characterizations of the SMP scaffolds merit further investigation. The objective of this project is to design a novel type of SMP foam with sufficient mechanical and physical characteristics, good biocompatibility, significant effects on cell behaviors, and successful bone-remodeling capacities for bone regeneration. Accordingly, the project is divided into four sections, including SMP foams fabrication and characterization, in vitro biocompatibility of the SMP foams, the effect of shape memory on cell alignment, and SMP foam inducing bone regeneration in vivo. Polyurethane/isocyanate-modified hydroxyapaptite (imHA) based SMP foams were fabricated as bone scaffolds. The SMP foams exhibited a remarkable increase in mechanical properties with 27 times in modulus and 4 times in compressive stress better than its pristine SMP counterpart at body temperature while maintaining higher memory effects (20% more). In addition, the composite foams have advantages that can match the trabecular bone in i) pore size (ranging from 534 to 797 μm and average trabecular bone is 600 μm), porosity (50-60%) and pore interconnectivity (99%), ii) compressive stress (2-14 Mpa) and modulus (109-1100 Mpa), and iii) body temperature responsive shape recovery (Rf >90%, Rr up to 100%). These results prove the effectiveness of imHA nanoparticles as inorganic corsslinks in the SMP foams in terms of resolving conflicting factors (the mechanical properties and shape memory performance, and the porosity and mechanical properties) to achieve optimal properties. These results ultimately indicate that the SMP can provide an ideal choice by overcoming the disadvantages of traditional polymer foams in terms of insufficient mechanical properties and inconvenience in operation. Biocompatibility in vitro has been evaluated in terms of cytotoxicity, cell attachment, cell proliferation and cell infiltration. The study clearly demonstrated the SMP foam has good biocompatibility in vitro. In the first place for cytotoxicity tests, results showed that cells have nearly 100% cell activity after cultivation with the extract of SMP foams compared with the positive control, demonstrating that the SMP foams have no cytotoxicity. Cells, which were attached on the SMP foams regardless of the different pore structures and contents of imHA nanoparticles, displayed normal morphology and proliferation in all cases. In addition, after quantitative analysis, the depth of cell infiltration showed increased depth of infiltration from 89 μm at day 1 to 438 μm at day 11 after cultivation. These results determined the SMP foams as bone scaffolds have good biocompatibility in vitro, proving insight into their potential applications in bone tissue engineering and bone regeneration. The effect of the SMP foam on controlling cell behaviors was also tested. Cells attached on the compact SMP foam showed an aligned arrangement perpendicularly to the compressive strain. After shape recovery activation at 37 °C, the attached cells reduced the alignment to the tangential direction of the pore edge. Furthermore, the cells exhibited normal proliferation performance and high cell viability during the shape memory activation process when compared with the static control groups. This work indicates that the SMP foam can control the cell behaviors through the programmed dynamic porous structure changes. Bone remodeling capacities of the SMP foam as a bone scaffold was determined using a rabbit femoral defect model. Results showed the feasibility of minimally invasive deliveryand self-fitting function of the SMP foam as a bone scaffold through the rabbit femoral defect model. Theimplanted SMP foam could expand from the compact shape to fill the bone defect after thermal stimulation. In addition, it demonstrated excellent biocompatibility for bone tissue regeneration and facilitated the bone in growth and neovascularization. The Micro-CT analysis showed fast bone repairing. Histology analysis further suggested successful bone remodeling and neovascularization occurred. In addition, the rabbit femoral defect model also determined biomechanical properties of SMP foam as a bone scaffold. The results showed the bone stiffness for the SMP foam reached 100.22 MPa at 12 weeks after surgery, which was similar to that of the intact femur and significantly higher than the blank control group (72.2 MPa). Therefore, this study provided compelling evidence to prove that the SMP foam was highly potential in the treatment of bone defects as a bone scaffold due to its superior performance. In all, the polyurethane/imHA based SMP foams demonstrated 1) sufficient mechanical properties, pore structures and effective shape memory performance; 2) good biocompatibility; 3) significant effects on cell behaviors; and 4) successful bone-remodeling capacities. It could be concluded that the SMP foams are promising biomaterials for the treatment of bone defects with minimally invasive surgery. The research may help to develop a new approach for bone tissue engineering.