Promoting bone regeneration by 3D-printed poly(glycolic acid)/hydroxyapatite composite scaffolds
Graphical abstract
Schematic diagram of the 3D-printed poly(glycolic acid)/hydroxyapatite composite scaffold and characterization.
Introduction
Tissue engineering is a prospective approach to restore critically defective tissues and organs that cannot be repaired by spontaneous healing and ordinary medical treatments in response to expanding demands of regenerative medicine [1], [2], [3], [4]. The human body is composed of complex types of tissues, including skin, adipose, muscle, vascular, endothelial, cartilage, ligament, and bone. Among these tissues, the bone is important as the skeletal framework and for the protection of biological organs [5], [6], [7], [8], [9], [10], [11], [12]. Bone has higher mechanical strength and lower density than most other tissues. Therefore, the ongoing research on bone tissue regeneration in biomedical fields is important.
Two critical considerations for bone tissue regeneration are mechanical strength and structural formability of bone grafts and scaffolds to mend defective sites. To secure the above considerations, optimized combinations of scaffold materials and fabrication processes are major factors for specific tissue restoration. Bone consists primarily of type I collagen that is mineralized with calcium phosphate crystals. Bone comprises an outer shell of dense, compact bone, whereas the inner region comprises thin networks of bone called trabeculae [3], [6]. Calcium phosphate compounds, such as HAp (hydroxyapatite; Ca5(PO4)3OH) and β-tricalcium phosphate (β-TCP; Ca3(PO4)2), are mainly used for bone grafts [5], [6]. HAp is a calcium phosphate compound that mostly consists of cortical and spongy bones. Advantages of HAp include good binding to bone, bioactivity, biocompatibility, and adequate osteoconductivity. However, it is important to consider certain disadvantages of the sintered form of calcium phosphate compounds as bioceramic materials. Porous scaffolds for patient-customized defects should have not only mechanical strength but also precise 3D formability, with uniform interconnected pores [2], [3], [4], [5]. Hence, a combination of biodegradable polymeric materials is necessary to obtain scaffold structures with reasonable mechanical strength. In general, materials used for 3D scaffolds in tissue regeneration are biocompatible and mainly consist of aliphatic biodegradable polyester materials that are degraded in vivo [1], [2], [3], [4], [5], [8], [12], [13], [14], [15], [16], [17]. Some researchers have reported that combinations of polymeric biomaterials with ceramic compounds, such as poly(lactic acid), polycaprolactone, alginate, and β-TCP, achieve sufficient bone strength and formability by 3D printing of bone tissue scaffolds [7], [8], [10], [13]. Compared to other biomedical polymers, poly(glycolic acid) (PGA) has high crystallinity, a Young’s modulus of 7.0 GPa, and a melting temperature of approximately 230 °C, with greater mechanical strength in comparison to other biodegradable polymers [12], [18], [19]. PGA is a suitable scaffold for bone, cartilage, and tooth regeneration because its mechanical strength is similar to that of human bones. In addition, PGA improves cell adhesion, proliferation, migration, and differentiation for rapid tissue regeneration.
However, the morphology and function of regenerated tissues after severe damage cannot be perfectly restored to the organizational continuity of the original tissues. Therefore, advanced scaffolds that serve as morphological guides for connecting and growing cells are important. 3D scaffolds for tissue engineering are porous, enabling increased mass exchange efficiency of seeded cells to proliferate and metabolize the structure [1], [2], [3], [4]. In particular, combinations of tissue engineering with 3D printing technology may enable new possibilities for intact tissue restoration by printing patient-specific porous 3D scaffolds [16], [17], [18], [19], [20]. 3D printing technology is an additive manufacturing method using digital data obtained through 3D scanning or modeling via a lamination process. In the field of tissue engineering, biocompatible thermoplastics could be applied for fused deposition modeling [[21], [22], [23], [24]]. For 3D printing, customization according to the actual body defects is possible, based on medical imaging (computerized tomography with x-ray and magnetic resonance imaging), to control the internal shape and uniform voids of the structure using computer-aided design (CAD) databases [20].
Our aim was to investigate the structural formability, mechanical strength, and cell growth using bone scaffolds of polymer (PGA)/ceramic (HAp) composite fabricated using 3D printing technology (Fig. 1).
Section snippets
3D modeling and printing of PGA/HAp composite scaffolds
PGA (pellets, Mw 80,000) were purchased from Meta Biomed Co., Ltd. (Korea) and kept in a vacuum package (4 °C). HAp nanoparticles were obtained from Sigma-Aldrich (USA). The aggregated HAp particles were ground using a laboratory porcelain mortar and pestle. Then, the HAp powder was separated using a sieve pan and kept in a vacuum chamber before use. The mean HAp particle size was calculated as 240 ± 80 nm (n = 30). The melting point of the PGA was measured using a differential scanning calorimeter
Results and discussion
Promoting hard tissue regeneration is an important objective in intact restoration of bone defects. Dimension-customized PGA scaffolds can guide and facilitate the proliferation of osteoblasts based on the critical size of bone defects [25]. In this study, a 3D-printed PGA scaffold containing HAp particles was prepared for promoting the regeneration of defective bone. The optimal mixture ratios of the PGA/HAp composite scaffolds were investigated and evaluated for bone tissue engineering
Conclusions
Porous PGA/HAp composite scaffolds containing 7.5, 10.0, 12.5, and 15.0 wt% of HAp were fabricated by 3D printing. The PGA/HAp 12.5 wt% group showed the highest compressive modulus values and a predominant proliferation of osteoblasts in comparison to the other groups. The biodegradation rates of the PGA/HAp composite scaffolds were increased in proportion to the HAp ratio. In in vivo animal experiments, the PGA/HAp group exhibited significant bone regeneration, with superior bone mineral
Declaration of interests
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.
Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgements
This work was supported by the National Research Foundation of Korea (NRF) grants (2017R1A2B4005736, 2020R1I1A3072735) and the Grand Information Technology Research Center Program (IITP-2020-2020-0-01612) through the Institute of Information & Communications Technology and Planning & Evaluation (IITP) funded by the Ministry of Science and ICT (MSIT), Korea.
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T. Yeo and Y.-G. Ko contributed equally to this work.