Advances in Biodegradable 3D Printed Scaffolds with Carbon-Based Nanomaterials for Bone Regeneration

Abstract

Bone possesses an inherent capacity to fix itself. However, when a defect larger than a critical size appears, external solutions must be applied. Traditionally, an autograft has been the most used solution in these situations. However, it presents some issues such as donor-site morbidity. In this context, porous biodegradable scaffolds have emerged as an interesting solution. They act as external support for cell growth and degrade when the defect is repaired. For an adequate performance, these scaffolds must meet specific requirements: biocompatibility, interconnected porosity, mechanical properties and biodegradability. To obtain the required porosity, many methods have conventionally been used (e.g., electrospinning, freeze-drying and salt-leaching). However, from the development of additive manufacturing methods a promising solution for this application has been proposed since such methods allow the complete customisation and control of scaffold geometry and porosity. Furthermore, carbon-based nanomaterials present the potential to impart osteoconductivity and antimicrobial properties and reinforce the matrix from a mechanical perspective. These properties make them ideal for use as nanomaterials to improve the properties and performance of scaffolds for bone tissue engineering. This work explores the potential research opportunities and challenges of 3D printed biodegradable composite-based scaffolds containing carbon-based nanomaterials for bone tissue engineering applications.

Keywords: additive manufacturing; biodegradable scaffolds; bone tissue engineering; carbon-based nanomaterials.

Figure 1

Bone defect healing: from self-healing to bone tissue engineering.

Figure 2

Inhibition of crack propagation by graphene in bioactive glass scaffold by different mechanisms: (a–c) crack deflection, crack bridging and graphene pull-out; (d) termination of crack growth at the crack tip [73].

Figure 3

Carbon-based nanomaterials (modified from [117]).

Figure 4

Live (green) and dead (red) MC3T3-E1 cells seeded on poly ε-caprolactone (PCL)-coated bioactive glass with different percentages of graphene. (a–c) Without graphene, (d–f) 1 wt.% graphene (G), (g–i) 3 wt.% G, (j–l) 5 wt.% G and (m–p) 10 wt.% G. After 7 days, the density of cells on G-containing scaffolds was higher than without G. However, after 14 days of incubation, a decrease in cell viability is observed due to the presence of G (reprinted from [170] with permission from Elsevier).

Figure 5

MC3T3 osteoblasts viability and proliferation measured by fluorescence intensity for G-containing PCL scaffolds. The higher the G content, the higher the cell proliferation rate. (*) Statistical analysis difference p < 0.05; (**) p < 0.01; (***) p < 0.001 (reprinted from [93], with permission from Elsevier).

Figure 6

Effect of mean pore size of collagen-glycosaminoglycan scaffolds on MC3T3-E1 cell attachment and proliferation at different time points: at 24 h (A), at 48 h (B) and 7 days (C). The relation between mean pore size and cell response is non-linear (reprinted from [198], with permission from Elsevier).

Figure 7

SEM images of PCL scaffolds with different percentages of Graphene oxide (GO), manufactured by Fused Deposition Modeling (FDM). Surface roughness and irregularity increased with the addition of GO. The average diameter of the fibres did not change with GO (reprinted from [260], with permission from Elsevier).

Figure 8

Photographs and cell viability (live cells in green and dead cells in red) of poly (lactic-co-glycolide) (PLG) scaffolds loaded with G manufactured by Direct Ink Writing (DIW). An increase in cell viability was produced when G was added (reprinted with permission from [268]. Copyright 2015 American Chemical Society).

Figure 9

Preparation of poly(vinyl alcohol) (PVA)-GO powder for Selective Laser Sintering (SLS) printing: (a) SEM image of initial PVA powder; (b) TEM image of initial GO; (c) photographs of GO/PVA suspersion in deionized water after ultrasonication; (d,e) SEM images of the composite powder after evaporation of water [98].

Figure 10

Polylactic acid (PLA)/PUA gyroid scaffolds manufactured by (a,b) Stereolithography (SLA) [238] and (c,d) Digital Light Processing (DLP) [240]. The addition of nanomaterials did not affect the printing process.

Figure 11

(A) Morphology of bone growth on CS/PCL scaffold with (G10) and without (G0) graphene manufactured by FDM. Images took by μ-CT. (B) Relative bone mass volume (BV/TV) at fixed-sized critical lesion ar different times. It is seen how the presence of G increased the bone growth rate (reprinted from [68], with permission from Elsevier).

Figure 12

Ceramic parts printed by DIW with and without GO. (A) Images of scaffolds produced with GO added to the ink (reprinted from [70], with permission from Elsevier); (B) photographs of scaffolds produced (a) without nanomaterials, (b) with 0.25 wt.% and 0.75 wt.% of nanomaterials added by infiltration into the pores (reprinted from [69], with permission from Elsevier); (C) Tricalcium phosphate (TCP) disks without and with GO coating (reprinted from [54], with permission from Elsevier).

Figure 13

(a) SEM images of PCL/Hydroxyapatite (HA)/multiwalled carbon nanotube (MWCNT) scaffold fabricated using DIW. (b) Images with higher magnification. MWCNTs that were incorporated at a low level of loading were well-dispersed within the polymer matrix, which increased the mechanical properties (reprinted from [274], with permission from Elsevier).

Figure 14

Images of Graphene-CaSiO₃ porous scaffold fabricated using SLS (left) and variation in fracture toughness on addition of G (right). There was an optimal level of G loading in terms of fracture toughness due to the inability to disperse the G within the matrix [275].