3D-printed biodegradable composite scaffolds with significantly enhanced mechanical properties via the combination of binder jetting and capillary rise infiltration process
Introduction
In tissue engineering aimed at replacing or restoring the lost or damaged tissues in the human body, 3D tissue engineering scaffolds are intended to act as cell growth platforms for cell repair and simultaneously act as a physical support for lost tissues [1], [2]. An ideal scaffold would transfer its role to the restored organization and degrade after completing its role of organizing recovery because there would be no requirement for secondary operation for scaffold removal [3]. Moreover, it should have an appropriate porous structure that can allow cell adherence, vascularization, and nutrient and metabolite diffusion [4], [5]. For hard tissue scaffolds that replace hard tissues, including bones and teeth, the scaffolds must possess mechanical and biological properties that are similar to those of native physiological tissues at the defect site [6].
Biodegradable, polymer-based biomaterial scaffolds are specifically used to regenerate bone tissues after traumas or tooth extractions [7], [8], [9]. This not only overcomes the stress concentration phenomenon, which is a disadvantage of the conventional bio-inert metals (such as titanium or cobalt chromium alloys, or ceramics such as brittle alumina and zirconia) but also benefits from polymer material characteristics, including biocompatibility and biodegradability [10], [11], [12]. Synthetic polymers with excellent physical properties are extensively used to fabricate polymer scaffolds. The typically used biodegradable polymers include polylactic acid (PLA), polyethylene glycol, and polycaprolactone (PCL) [13]. Among these, PCL, which is a biodegradable polymer, is extensively used because of its unique physical strength; thus, it is employed for hard tissue engineering in various domains [14], [15], [16]. One of the advantages of biodegradable polymer scaffolds is that they are easy to process. They are produced through various approaches, including solvent casting with particulate leaching, gas forming, phase separation, and emulsion freeze-drying; accordingly they can be applied in various fields. Recently, the 3D printing process, called additive manufacturing, has received considerable attention in the tissue engineering field because of its ability to design and fabricate complex structures with high reliability [17], [18], [19]. The 3D printing technique, combined with computer-aided design (CAD) systems, can be customized for tissues that have suffered different types of loss or damage for each patient [20], [21], [22], [23].
Generally, from an application viewpoint in hard tissue engineering, the mechanical properties of biodegradable polymer scaffolds are inferior to those of other materials such as ceramics and metals [24]. Moreover, the biocompatibility of biodegradable polymer scaffolds must be enhanced to broaden their applications for hard tissue engineering. Therefore, to overcome these limitations while retaining the advantages of biodegradable polymer scaffolds, polymer-based composite scaffolds have been considered as promising candidate materials with enhanced mechanical and biological properties [25], [26], [27], [28]. Among polymer-ceramic composite scaffolds, calcium-phosphate-based (CaP) ceramic materials, including hydroxyapatite (HA), tricalcium phosphate (TCP), and biphasic calcium phosphates (BCP) (which is a combination of HA and TCP), are most commonly used as fillers or reinforcements because of their excellent biocompatibility, osteoconductive characteristics, and satisfactory mechanical properties [29], [30], [31], [32], [33], [34]. Based on these advantages, PCL/CaP-based polymer-ceramic composite have been extensively studied [35]. According to several previous studies, when PCL/CaP composite scaffolds are developed, the desired cell properties and physical properties can be enhanced, and other polymers, such as PLA, collagen, starch, could be added to further improve the desired properties [36], [37], [38], [39]. However, to facilitate extrusion for performing 3D printing through such an extrusion process (such as fused filament fabrication (FFF)), the filler concentration in the polymer matrix was up to ~30–40 wt% owing to the printability; thus, the enhancement in the mechanical properties was limited [27], [40], [41]. In addition, there are several papers that have shown reinforcement of binder jetted BCP or HA scaffolds by coating them with PCL solutions [42], [43], [44]. With the viscous nature of PCL solutions it is difficult to fill the micropores inside the scaffolds which can limit the enhancement in mechanical properties.
Therefore, in this study, we propose a different approach for fabricating the PCL/CaP composite with significantly enhanced mechanical properties. PCL, a polymer material, was used both as a matrix and a filler, and CaP was used as the primary material for the structure. The mechanical integrity of the scaffold was enhanced using the polymer to fill the pores of the ceramic structure. By fabricating a composite material using the idea, we hypothesized the final product could meet the requirements that can enhance both mechanical and biological properties. To confirm our hypothesis, we designed the experiment with binder jetting incorporated with the capillary rise infiltration (CaRI) process as follows. First, a calcium sulfate hemihydrate (CSH) scaffold designed by CAD was fabricated using a BJ-based 3D printing. Through a hydrothermal treatment process, followed by heat treatment, CSH was transformed into BCP, which offered two advantages: high bioactivity of HA and biodegradability of TCP. Finally, using the CaRI process, the transformed BCP scaffold was filled with melted PCL. The structural morphologies and chemical structures of the PCL/BCP composite scaffolds were examined using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and micro-computed tomography (μ-CT). The surface topography and roughness of produced PCL/BCP composite scaffolds were evaluated using confocal laser microscopy (CLM). Moreover, the mechanical behaviors of scaffolds were evaluated using mechanical compression tests. Furthermore, the biocompatibility of as-prepared scaffolds was observed by in-vitro cell attachment, proliferation, and differentiation tests using pre-osteoblast cells.
Section snippets
Sample preparation
Commercially available CSH powder (zp150) and 2-pyrrolidone (zb63) supplied by 3D Systems Inc. (USA) were used as starting materials for 3D printing. The structures of the desired CSH scaffolds, i.e., with ~50% porosity and 1000 µm pore size, were modeled using SolidWorks 2013 (Solid Works Corporation, Santa Monica, CA, USA) and exported as an STL file to the printer. Modeling was then performed by layering a 12-mm3 of cube with alternating 1000-μm strut and 1000-μm spacing in each plane. For
Characterization of the 3D printed BCP/PCL scaffolds
Fig. 1 shows the FESEM images of surface morphology and shows the optical image of the overall shape of 3D-printed scaffolds. From the optical image of the inset, all specimens appear to have the same overall shape and there is no significant difference. The original scaffold printed by CSH had a well-controlled porous structure that matched the initial design, which had a pore size of ~1000 µm, generated in a layer-by-layer manner without any cracks or defects (Fig. 1(A)). After hydrothermal
Conclusion
In this study, novel PCL/BCP composite scaffolds with significantly enhanced mechanical properties in which a ceramic reinforcing strut was first formed, followed by polymer infiltration using the BJ-based 3D printing technique conjugated with the CaRI process. By sequential hydrothermal and heat treatments, the 3D-printed CSH scaffold was successfully transformed into the BCP scaffold. Melted PCL was infiltrated into the micropores (57% porosity) of the resulting BCP scaffold by capillary
CRediT authorship contribution statement
Ji-Ho Ahn: Conceptualization, Methodology, Validation, Investigation. Jinyoung Kim: Methodology, Validation, Investigation, Writing - original draft. Ginam Han: Validation, Investigation. DongEung Kim: Investigation. Kwang-Hee Cheon: Investigation. Hyun Lee: Validation. Hyoun-Ee Kim: Supervision, Project administration. Young-Jig Kim: Project administration. Tae-Sik Jang: Conceptualization, Methodology, Writing - review & editing. Hyun-Do Jung: Conceptualization, Methodology, Writing - original
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was supported by The Catholic University of Korea, Research Fund, 2020 and the Basic Science Research Program [No. 2020R1F1A1072103] through the National Research Foundation of Korea funded by the Korea government (MSIT).
References (88)
- et al.
Construction of tantalum/poly (ether imide) coatings on magnesium implants with both corrosion protection and osseointegration properties
Bioact. Mater.
(2021) - et al.
Biodegradable bone implants in orthopedic applications: a review
Biocybern. Biomed. Eng.
(2020) - et al.
Combination of fused deposition modeling and gas foaming technique to fabricated hierarchical macro/microporous polymer scaffolds
Mater. Des.
(2016) - et al.
Absorbable polyglycolide devices in trauma and bone surgery
Biomaterials
(1997) - et al.
Three dimensional electrospun PCL/PLA blend nanofibrous scaffolds with significantly improved stem cells osteogenic differentiation and cranial bone formation
Biomaterials
(2017) - et al.
Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering
Biomaterials
(2005) - et al.
Fabrication of strong, bioactive vascular grafts with PCL/collagen and PCL/silica bilayers for small-diameter vascular applications
Mater. Des.
(2019) - et al.
Bone tissue engineering using 3D printing
Mater. Today
(2013) - et al.
Clinical, industrial, and research perspectives on powder bed fusion additively manufactured metal implants
Addit. Manuf.
(2019) - et al.
Carbon fiber reinforced PEEK composites based on 3D-printing technology for orthopedic and dental applications
J. Clin. Med.
(2019)
Preliminary investigation of poly-ether-ether-ketone based on fused deposition modeling for medical applications
Materials
Fabrication of poly (lactic acid)/Ti composite scaffolds with enhanced mechanical properties and biocompatibility via fused filament fabrication (FFF)–based 3D printing
Addit. Manuf.
Study of the matrix-filler interface in PLA/Mg composites manufactured by Material Extrusion using a colloidal feedstock
Addit. Manuf.
3D-printed PCL/bioglass (BGS-7) composite scaffolds with high toughness and cell-responses for bone tissue regeneration
J. Ind. Eng. Chem.
Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering
Biomaterials
Preparation of polymer/calcium phosphate porous composite as bone tissue scaffolds
Mater. Sci. Eng. C
Preparation of dexamethasone-loaded biphasic calcium phosphate nanoparticles/collagen porous composite scaffolds for bone tissue engineering
Acta Biomater.
New composite materials prepared by calcium phosphate precipitation in chitosan/collagen/hyaluronic acid sponge cross-linked by EDC/NHS
Int. J. Biol. Macromol.
Porous calcium phosphate-collagen composite microspheres for effective growth factor delivery and bone tissue regeneration
Mater. Sci. Eng. C
Surface immobilization of biphasic calcium phosphate nanoparticles on 3D printed poly (caprolactone) scaffolds enhances osteogenesis and bone tissue regeneration
J. Ind. Eng. Chem.
3D printed PCL/SrHA scaffold for enhanced bone regeneration
Chem. Eng. J.
Preparation and characterization of PLA/PCL/HA composite scaffolds using indirect 3D printing for bone tissue engineering
Mater. Sci. Eng. C
Effects of amylose content on the mechanical properties of starch-hydroxyapatite 3D printed bone scaffolds
Addit. Manuf.
Starch-hydroxyapatite composite bone scaffold fabrication utilizing a slurry extrusion-based solid freeform fabricator
Addit. Manuf.
The enhancement of hydroxyapatite thermal stability by Al doping
J. Mater. Res. Technol.
Dissolution of calcium-deficient hydroxyapatite synthesized at different conditions
Mater. Charact.
Biphasic calcium phosphates bioceramics (HA/TCP): concept, physicochemical properties and the impact of standardization of study protocols in biomaterials research
Mater. Sci. Eng. C
The influence hydroxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coated with hydroxyapatite–PCL composites
Biomaterials
Enhanced mechanical performance and biological evaluation of a PLGA coated β-TCP composite scaffold for load-bearing applications
Eur. Polym. J.
Development of three-dimensional printing polymer-ceramic scaffolds with enhanced compressive properties and tuneable resorption
Mater. Sci. Eng. C
Production and bio-corrosion resistance of porous magnesium with hydroxyapatite coating for biomedical applications
Mater. Lett.
Biomimetic porous Mg with tunable mechanical properties and biodegradation rates for bone regeneration
Acta Biomater.
Novel strategy for mechanically tunable and bioactive metal implants
Biomaterials
A graphene oxide-Ag co-dispersing nanosystem: dual synergistic effects on antibacterial activities and mechanical properties of polymer scaffolds
Chem. Eng. J.
Porogen-based solid freeform fabrication of polycaprolactone–calcium phosphate scaffolds for tissue engineering
Biomaterials
Effects of surface area and topography on 3D printed tricalcium phosphate scaffolds for bone grafting applications
Addit. Manuf.
Fabrication of three-dimensional polycaprolactone/hydroxyapatite tissue scaffolds and osteoblast-scaffold interactions in vitro
Biomaterials
Microstructure and mechanical behavior of porous sintered steels
Mater. Sci. Eng. A
Effect of micropores on the microstructure and mechanical properties of porous Cu-Sn-Ti composites
Mater. Sci. Eng. A
Quantitative analysis of cell proliferation and orientation on substrata with uniform parallel surface micro-grooves
Biomaterials
Importance of dual delivery systems for bone tissue engineering
J. Control. Release
Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair
Adv. Drug Deliv. Rev.
Bone fracture healing: cell therapy in delayed unions and nonunions
Bone
Biodegradable polymer scaffolds
J. Mater. Chem. B
Cited by (0)
- 1
The authors contributed equally.