Large bone defects with limited intrinsic regenerative potential represent a major surgical challenge and are associated with a high socio-economic burden and severe reduction in the quality of life. Tissue engineering approaches offer the possibility to induce new functional bone regeneration, with the biomimetic scaffold serving as a bridge to create a microenvironment that enables a regenerative niche at the site of damage. Magnetic nanoparticles have emerged as a potential tool in bone tissue engineering that leverages the inherent magnetism of magnetic nano particles in cellular microenvironments providing direction in enhancing the osteoinductive, osteoconductive and angiogenic properties in the design of scaffolds. There are conflicting opinions and reports on the role of MNPs on these scaffolds, such as the true role of magnetism, the application of external magnetic fields in combination with MNPs, remote delivery of biomechanical stimuli in-vivo and magnetically controlled cell retention or bioactive agent delivery in promoting osteogenesis and angiogenesis.
Scaffold Material | MNP Composition | MNP Content within Scaffold | Magnetism Intensity (emu/g) | Osteogenic Impact | Mechanism | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
HA and Collagen [23] | HA and Collagen [61] | NI | 2.65% | NI | Enhanced bone maturity in-vivo, identified by improved mechanical properties. | Incongruous magnetic moment created by the distribution of MNPs within the scaffold. | |||||||
PCL [21] | PCL [59] | Maghemite | 7.9% | NI | Improved cell adhesion, proliferation and osteogenic differentiation (elevated ALP) of MSCs. | MNP incorporation generates a magnetic microenvironment. | |||||||
PCL [14] | PCL [52] | GdHA | 2.67% | NI | Greater cell attachment, spreading, proliferation and osteogenic differentiation (higher ALP, RUNX2) of MSCs. Improved mechanical properties. |
Gadolinium released entered cells and promoted cell cycle progression. Greater hydrophilicity and surface area facilitate protein adsorption. Reduced PCL fibre diameter increases scaffold strength. |
|||||||
PCL [24] | PCL [62] | FeHA | 4.5% | NI | Improved cell growth. Scaffold filled with new bone after just 4 weeks in-vivo. |
MNP incorporation generates a magnetic microenvironment. | |||||||
PCL [11] | PCL [49] | Magnetite | 5% 10% |
5%—1.6 10%—3.1 |
Greater cell adhesion, proliferation and osteogenic differentiation (enhanced cellular mineralisation) of MSCs. | Elevated hydrophilicity improved cell adhesion that facilitated proliferation and differentiation to follow. MNP incorporation generates a magnetic microenvironment. |
|||||||
PCL [18] | PCL [56] | Magnetite | 5%, 10%, 15%, 20% | 5%—1.0 20%—11.2 |
Better cell adhesion, spreading, penetration and osteogenic differentiation (ALP, COL-1, OPN, BSP) of MSCs. Histology showed higher blood vessel formation and better integration with the host tissue in-vivo. Enhanced mechanical properties. |
MNP incorporation generates a magnetic microenvironment. Controlled degradation rate allows ingrowth of cells and vascularisation. Strong chemical interaction between MNPs and polymer chains. |
|||||||
PCL and PLGA [10] | PCL and PLGA [48] | Maghemite | 16.4% | 3.56 | Improved cell adhesion, spreading and osteogenic differentiation (higher ALP, RUNX2, OCN, COL-1 and bone mineralisation) of ADSCs. Better mechanical properties. |
Greater hydrophilicity and protein adsorptions facilitate cell attachment. Higher gene expression of a transmembrane magnetoreceptor ISCA1-osteogenic enhancement as a result of transmembrane effect of MNPs. |
|||||||
PLLA and PGA [22] | PLLA and PGA [60] | Magnetite | 2.5%, 5%, 7.5%, 10% | 2.5%—1.66 10%—8.51 |
Greater cell adhesion, spreading, proliferation and osteogenic differentiation (ALP) of MG63 cells. Improved mechanical properties. Better BMD, BVF, fusion and blood vessel formation in-vivo. |
Improved hydrophilicity and magnetic microenvironments facilitate improved cellular activity. MNPs resist deformation of the polymer chains. Microenvironment promoted adhesion, migration and differentiation of osteocytes in-vivo. |
|||||||
PCL and Mesoporous Bioactive glass [20] | PCL and Mesoporous Bioactive glass [58] | Magnetite | 5%, 10%, 15% | 5%—3.1 10%—6.2 15%—9.3 |
Increased cell adhesion, proliferation and osteogenic differentiation (elevated ALP, RUNX2, OCN, BMP-2 and COL-1) of MSCs. | Improved hierarchal pore structure. MNP incorporation generates a magnetic microenvironment. |
|||||||
CPC [13] | CPC [51] | Magnetite | 0.05–5% | 0.1%—0.05 1%—0.35 |
Greater cell adhesion, spreading, proliferation and osteogenic differentiation (increased ALP) of BMSCs. Improved mechanical properties. |
Altered surface morphology- change in crystal shape and reduced size increased the surface area for adhesion of proteins involved in cell adhesion. MNP incorporation generates a magnetic microenvironment. |
|||||||
CPC [12] | CPC [50] | Maghemite | NI | NI | Enhanced cell attachment, spreading, proliferation and osteogenic differentiation (increased ALP, RUNX2, OCN, COL-1) of DPSCs. | Altered surface morphology-reduced crystal size increased the surface area for adhesion of proteins involved in cell adhesion. MNPs released by the degrading scaffolds and interact with cells via membrane adsorption and internalisation. |
|||||||
CPC [15] | CPC [53] | Maghemite | 1–6% | NI | Improved cell adhesion, spreading, proliferation and osteogenic differentiation (increased ALP, RUNX2, OCN, COL-1) of DPSCs. Enhanced the mechanical properties. |
Greater hydrophilicity and improved nanostructure facilitated cell adhesion and spreading. The WNT signalling pathway is activated and mediates proliferation osteogenic differentiation upon magnetic stimulation. Cells internalise released MNPs. |
|||||||
Gelatin and Siloxane [16] | Gelatin and Siloxane [54] | Magnetite | 1–3% | 1%—0.24 3%—0.64 |
Greater cell adhesion, proliferation and osteogenic differentiation (greater ALP and mineralisation) of MSCs. Improved mechanical properties. |
Improved hydrophilicity allowed better cell adhesion. MNP incorporation generates a magnetic microenvironment. |
|||||||
Bioglass and Chitosan [19] | Bioglass and Chitosan [57] | SrFe | 12 | O | 19 | 1:7, 1:3 (ratio of SrFe | 12 | O | 19 | to Bioglass) | 1:7–4.44 1:3–7.68 |
Enhanced cell adhesion, spreading, proliferation and osteogenic differentiation (increased ALP, RUNX2, OCN, COL-1, BMP-2) of BMSCs. Greater bone mineralisation, BMD and BV/TV in-vivo. |
Proliferation and osteogenic differentiation are mediated by BMP-2/Smad/RUNX2 pathway upon magnetic stimulation. |
Chitosan and Collagen [17] | Chitosan and Collagen [55] | Magnetite | NI | 0.025 | Improved cell adhesion, proliferation and osteogenic differentiation (better mineralisation) in pre-osteoblasts. Enhanced bony ingrowth, BMD and BVF in-vivo. Better mechanical properties. |
Improved hierarchical nanostructure- surface roughness and interconnected porosity. This can improve cell adhesion, cell penetration as well as nutrient transfer and flow transportation in the scaffold. |