Fabrication of poly(lactic acid)/Ti composite scaffolds with enhanced mechanical properties and biocompatibility via fused filament fabrication (FFF)–based 3D printing

Highlights

• 3D-printed PLA/Ti scaffolds with tailored porosity and pore size were fabricated via fused filament fabrication (FFF).

• Thermal properties of PLA/Ti filaments were changed by the addition of Ti.

• 5–10 vol% of Ti enhanced the mechanical properties of 3D-printed PLA/Ti scaffolds.

• In vitro assays showed good cell responses in PLA/Ti scaffolds.

• 3D-printed PLA/Ti scaffolds have potential as bone substitutes for tissue engineering.

Abstract

Ideal bone substitutes should ensure good integration with bone tissue and are therefore required to exhibit good mechanical stability and biocompatibility. Consequently, the high elastic modulus (similar to that of bone), thermoplasticity, and biocompatibility of poly(lactic acid) (PLA) make it well suited for the fabrication of such substitutes by fused filament fabrication (FFF)-based 3D printing. However, the demands of present-day applications require the mechanical and biological properties of PLA to be further improved. Herein, we fabricated PLA/Ti composite scaffolds by FFF-based 3D printing and used thermogravimetric analysis to confirm the homogenous dispersion of Ti particles in the PLA matrix at loadings of 5–20 vol%. Notably, the thermal stability of these composites and the crystallization temperature/crystallinity degree of PLA therein decreased with increasing Ti content, while the corresponding glass transition temperature and melting temperature concomitantly increased. The compressive and tensile strengths of PLA/Ti composites increased with Ti increasing loading until it reached 10 vol% and were within the range of real bone values, while the impact strengths of the above composites significantly exceeded that of pure PLA. The incorporation of Ti resulted in enhanced in vitro biocompatibility, promoting the initial attachment, proliferation, and differentiation of pre-osteoblast cells, which allowed us to conclude that the prepared PLA/Ti composite scaffolds with enhanced mechanical and biological properties are promising candidates for bone tissue engineering applications.

Introduction

Bone substitutes are extensively used to heal bone defects and diseases caused by trauma, osteoporosis, and cancer [[1], [2], [3], [4]], allowing one to overcome the drawbacks of conventional healing methods. For example, although auto- and allografts which are extracted tissues or organs from oneself and other donor, respectively, are well suited for defect filling, their sources are very limited [5,6], while the use of xenografts, which are obtained from other species, is complicated by immune response problems [7]. In view of the fact that ideal bone substitutes are required to provide proper mechanical stability and enable the adherence, proliferation, and differentiation of cells responsible for bone regeneration [8,9], porous scaffolds that allow for better implant-bone integration and can be loaded with drugs or growth factors for better bioactivity are commonly used in tissue engineering [10]. Although artificial bone substitutes are commonly fabricated from metals and ceramics because of the sufficient strength and biocompatibility of these materials [11,12], the elastic moduli of both ceramics and metals significantly exceed that of bone, which results in unbalanced load transfer and can cause bone resorption due to the stress shielding effect [13]. Additionally, other issues to consider include the intrinsic brittleness of ceramics, which limits their clinical usage as bone scaffolds [14], and artifacts observed near metal implants during MRI and CT scanning that are caused by misregistration and beam hardening, respectively, and interfere with accurate analysis [15,16].

The above situation has inspired studies of various biopolymers such as polyetheretherketone (PEEK), polycarprolactone, and poly(lactic acid) (PLA) as potential bone-substituting materials [[17], [18], [19], [20], [21], [22]]. Among those candidates, PLA has been widely utilized since it has been approved by the USA Food and Drug Administration (FDA) for the fabrication of fracture fixation implants, drug release systems, surgical suture, dental implant coatings, and biomedical imaging/detection [[23], [24], [25], [26], [27]]. However, despite the above advantages, the biocompatibility and mechanical properties of PLA need to be further enhanced to broaden its applications in the field of hard tissue engineering.

Numerous studies were conducted to enhance the biocompatibility and mechanical properties of PLA via the incorporation of additives such as other polymers, inorganic particles, and fibers [[28], [29], [30], [31], [32], [33], [34], [35]]. In particular, the use of calcium phosphate (CaP)-based fillers was commonly adopted because of their excellent osteoconductive characteristics and good mechanical properties [[36], [37], [38], [39]]. These CaP-PLA composite scaffolds were fabricated via various methods including solvent casting, injection molding, extrusion, and additive manufacturing [[40], [41], [42], [43], [44], [45]]. Especially for fused filament fabrication (FFF) method, it has emerged as a promising technique because of its high reliability, simplicity, and material availability [46]. Moreover, the combination of FFF with computer-aided design (CAD) systems allows one to produce complicated and patient-customized scaffolds with well-controlled structures. However, the simple blending of CaP-based powders with PLA-containing polymers is not desired, since the high surface area of the former results in non-uniform distribution within the polymer matrix, which is detrimental to the physical properties of the thus obtained composites [47].

Herein, ductile Ti metal was chosen as an alternative PLA reinforcing agent owing to its high specific strength, chemical stability, and excellent biocompatibility under physiological conditions [11,48,49]. Homogeneous PLA/Ti filaments with Ti loadings of 0–20 vol% for FFF-based 3D printing were prepared using a shear mixer and a single-screw extruder, and porous PLA/Ti scaffolds with various Ti loadings were fabricated following the input design of the FFF process. The physiological characteristics and crystalline phases of as-obtained scaffolds were evaluated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). Scanning electron microscopy (SEM) and microcomputed tomography (μ-CT) were used to observe scaffold structures, while the corresponding mechanical properties were examined using compression, tensile, and Charpy impact tests. Finally, the biocompatibility of produced materials was probed by in vitro cell attachment, proliferation, and differentiation tests using pre-osteoblast cells.