3D Printing of Bioactive Ceramic Scaffolds for Bone Tissue Engineering
Received Date: Jun 11, 2018 / Accepted Date: Jun 15, 2018 / Published Date: Jun 22, 2018
Bone tissue engineering has emerged as an innovative and promising strategy for treating bone defects, in which a three-dimensional (3D) porous scaffold is loaded with tissue-inducing factors or specific cells to launch a tissue regeneration in a natural way [1,2]. A variety of materials, consisting of bimetallic materials, bioceramics, biopolymers or bio composites, have been proposed and used to fabricate scaffolds for bone tissue engineering over the last few decades, while the functions similar to natural bone remains a challenging task . Architecture, mechanical property and osteogenic ability are considered as the most critical characteristics for an ideal scaffold . Many bioceramic materials have high stiffness and bioactivity (i.e., their similarity to the mineral phase of natural bone) [5,6], which can act as a temporary framework for providing a suitable environment for cell adhesion, growth, and more explicitly help bone tissue regeneration. Bioceramics refer to a class of ceramic materials with specific biological or physiological function, and can be used directly in the human body or in applications related to the human body .
Scaffold is a 3D biocompatible structure that can mimic the properties of mechanical support, cellular activity and protein production through biochemical and mechanical interactions. Also, 3D scaffold provides a template for cell attachment and stimulates bone tissue formation in vivo [8,9]. Currently, there is an intensive concerning on the development of fabrication methods for enhancing the function of scaffolds. Traditional or regular methods to fabricate 3D porous scaffolds, such as particle leaching, foaming, or freeze-drying, have limitations to precisely control the overall architectures and internal pore connectivity [10,11]. Advanced additive manufacturing techniques, such as 3D printing, can control the architecture and pore structures precisely and produce custom-designed, computer-controlled tissue scaffolds, overcoming many limitations of current fabrication methods .
To date, much effort has been made to fabricate bioactive ceramic scaffolds by 3D printing techniques, and show great application promising in bone tissue engineering. A wide range of bioactive ceramics, such as hydroxyapatite (HA), beta-tricalcium phosphate (β-TCP), bioactive glass (BG) and calcium silicate (CS), similar in composition to the mineral phase of bone are of great clinical interest . Bioactive ceramic scaffolds could be implanted into bone defects and self-degrade in vivo. Importantly, bioactive ceramic scaffolds are able to react with physiological fluids, resulting in the formation of strong chemical-force bonding to bone tissues due to the formation of bone-like HA layers [14,15]. Nowadays, a variety of studies has reported on the relationships among the chemical compositions, bioactivity and the fabrication process of scaffolds, modification and so forth.
To date, 3D printing of pure bioactive ceramics has gained much progress. However, the development of composite inks quickly emerged as the technology grew, especially due to the development of direct ink writing printer. The main goal of using composite inks is to enhance ink properties such as process ability, printability, mechanics (stiffness) and bioactivity (to enhance cellular function and tissue integration) . HA, β-TCP, BG and CS are widely used as the inorganic biomaterials due to their excellent osteoconductivity . Polymeric biomaterials used for bone tissue engineering applications are usually biocompatible polymers (such as poly(lactic acid) (PLA), polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA)) or natural hydrogels (such as collagen, chitosan and alginate) . Much progress has been achieved on bioceramic/polymer composite scaffolds, bioceramic/hydrogel composite scaffolds, and multifunctional bioceramic-based scaffolds.
The advantage of biodegradable bioceramic/polymer composite scaffolds is that altering the organic/inorganic material composition or ratio can change the properties of the composite scaffolds to satisfy the requirements for bone tissue engineering. PLA, PCL, PLGA and so on are common biocompatible polymers used for bone tissue engineering applications. Also, these biopolymers can act as binders during the printing process. For example, Adam et al.  3D-printed a new synthetic osteoregenerative biomaterial, hyperelastic “bone” (HB), which is composed of 90 wt% HA and 10 wt% PCL or PLGA. The resulting 3D-printed HB exhibited excellent elastic mechanical properties (~32 to 67% strain to failure, ~4 to 11 MPa elastic modulus). Beyond these, HB became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors when implanted in vivo.
Hydrogels are three-dimensional polymer networks that can provide excellent “soft material” systems to mimic native extracellular matrix (ECM) microenvironments due to their tunable degradation, mechanics and functionality . Extrusion-based 3D printing systems are the most suitable methods to print bioceramic/hydrogel composite scaffolds. The classical approach to design bioceramic/ hydrogel composite scaffolds is to formulate a hydrogel solution firstly and incorporate ceramic powders into the hydrogel matrix that forms a network immediately after printing. The network could be physically or chemically cross-linked in response to an external stimulus (i.e. light, temperature, or ion concentration) . Common hydrogels for 3D printing are made from natural polymers such as alginate, gelatin, agar, cellulose, collagen, silk fibroin, hyaluronic acid, or from synthetic polymers such as poly(vinyl alcohol) (PVA), polyacrylamide, poly(ethylene glycol) (PEG), or a synthetic-natural mixture.
Generally, the hierarchical structure, surface and interface of biomaterials are important factors that influencing their biological properties. Bioactive ceramic scaffolds have been widely used for bone tissue engineering by optimizing their chemical composition and pore structure. Importantly, bioactive ceramic could be modified with various functional materials, and a variety of functional scaffolds have been developed for bone tissue engineering.
Many reports are there on the modification of bioactive ceramic scaffolds to achieve sustained drug delivery. For example, porous HA scaffolds were developed by coating rhBMP-2-delivery microspheres with collagen . The coating of rhBMP-2/collagen microspheres facilitated the adhesion of hMSCs, and the scaffolds can simultaneously achieve localized long-term controlled release of rhBMP-2 and bone regeneration, which provided a promising route for improving the treatment of bone defects.
For the treatment of bone defects caused by malignant bone tumors, functional 3D porous scaffolds that function in both tissue regeneration and tumor therapy are expected to address this need. Now, some functional materials were incorporated or combined with bioactive ceramic scaffold to fulfil more functionality, such as magnetic hyperthermia and photo thermal therapeutic properties. Yang et al.  3D printed bioactive glass scaffolds and functionalized them with black phosphorus (BP) nanosheets, the in situ phosphorusdriven, calcium-extracted bio mineralization of the intra-scaffold BP nanosheets enables both photo thermal ablation of osteosarcoma and the subsequent material-guided bone regeneration, which provides a feasible countermeasure for efficient localized treatment of osteosarcoma.
In summary, the shapes of bone defects caused by trauma, tumors or disease are often irregular. Together with modern imaging and computer aided manufacturing technologies, 3D printing can fabricate special shaped scaffolds rapidly and conveniently, which has greatly advanced the progress of bone tissue engineering. Further developments in 3D printing of bioactive ceramic scaffolds for bone tissue engineering will require scaffold design optimization, better knowledge of cell and organ physiology and most importantly, new bioactive ceramics that can be 3D-printed and also emulate the compositional, structural, and functional complexities of human natural bone.
The authors gratefully acknowledge the support by grants from the Science and Technology Commission of Shanghai Municipality (NO. 17060502400).
- Service RF (2000) Tissue engineers build new bone. Science 289: 1498-1500.
- Lopez-Heredia MA, Sohier J, Gaillard C, Quillard S, Dorget M, et al. (2008) Rapid prototyped porous titanium coated with calcium phosphate as a scaffold for bone tissue engineering. Biomaterials 29: 2608-2615.
- Ho CMB, Ng SH, Yoon YJ (2015) A review on 3D printed bioimplants. Int J Precis Eng Man 16: 1035-1046.
- Janicki P, Schmidmaier G (2011) What should be the characteristics of the ideal bone graft substitute? Combining scaffolds with growth factors and/or stem cells. Injury 42: S77-S81.
- Riau AK, Mondal D, Setiawan M, Palaniappan A, Yam GHF, et al. (2016) Functionalization of the Polymeric Surface with Bioceramic Nanoparticles via a Novel, Nonthermal Dip Coating Method. ACS Appl Mater Inter 8: 35565-35577.
- Fillingham YA, Cvetanovich GL, Haughom BD, Erickson BJ, Gitelis S (2016) Bioceramic bone graft substitute for treatment of unicameral bone cysts. J Orthop Surg 24: 222-227.
- Ebrahimi M, Botelho MG, Dorozhkin SV (2017) Biphasic calcium phosphates bioceramics (HA/TCP): Concept, physicochemical properties and the impact of standardization of study protocols in biomaterials research. Mater Sci Eng C Mater Biol Appl 71: 1293-1312.
- Salgado AJ, Coutinho OP, Reis RL (2004) Bone tissue engineering: state of the art and future trends. Macromol Biosci 4: 743-765.
- Tamjid E, Simchi A, Dunlop JWC, Fratzl P, Bagheri R, et al. (2013) Tissue growth into three-dimensional composite scaffolds with controlled micro-features and nanotopographical surfaces. J Biomed Mater Res Part A 101: 2796-2807.
- Shaunak S, Dhinsa BS, Khan WS (2017) The Role of 3D Modelling and Printing in Orthopaedic Tissue Engineering: A Review of the Current Literature. Curr Stem Cell Res Ther 12: 225-232.
- Zhu M, Zhang J, Zhao S, Zhu Y, (2015) Three-dimensional printing of cerium-incorporated mesoporous calcium-silicate scaffolds for bone repair. J Mater Sci 51: 836-844.
- Tack P, Victor J, Gemmel P, Annemans L (2016) 3D-printing techniques in a medical setting: a systematic literature review . Biomed Eng Online 15: 115.
- Guarino V, Causa F, Ambrosio L (2007) Bioactive scaffolds for bone and ligament tissue. Expert Rev Med Devices 4: 405-418.
- Kokubo T, Kim H-M, Kawashita M (2003) Novel bioactive materials with different mechanical properties. Biomaterials 24: 2161-2175.
- Gerhardt LC, Boccaccini AR (2010) Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering. Materials 3: 3867-3910.
- Meseguer-Olmo L, Vicente-Ortega V, Alcaraz-Banos M, Calvo-Guirado JL, Vallet-Regi M, et al. (2013) Invivo behavior of Si-hydroxyapatite/polycaprolactone/DMB scaffolds fabricated by 3D printing. J Biomed Mater Res Part A 101: 2038-2048.
- Wen Y, Xun S, Haoye M, Baichuan S, Peng C, et al. (2017) 3D printed porous ceramic scaffolds for bone tissue engineering: a review. Biomater Sci 5: 1690-1698.
- Wang X, Jiang M, Zhou ZW, Gou JH, Hui D (2017) 3D printing of polymer matrix composites: A review and prospective. Compos Part B-Eng 110: 442-458.
- Jakus AE, Rutz AL, Jordan SW, Kannan A, Mitchell SM, et al. (2016) Hyperelastic "bone": A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial. Sci Transl Med 8: 358-327.
- Seliktar D (2012) Designing Cell-Compatible Hydrogels for Biomedical Applications. Science 336: 1124-1128.
- Billiet T, Vandenhaute M, Schelfhout J, Van Vlierberghe S, Dubruel P (2012) A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials 33: 6020-6041.
- Wang H, Wu G, Zhang J, Zhou K, Yin B, et al. (2016) Osteogenic effect of controlled released rhBMP-2 in 3D printed porous hydroxyapatite scaffold. Colloid Surface 141: 491-498.
- Yang B, Yin J, Chen Y, Pan S, Yao H, at al. (2018) 2D-black-phosphorus-reinforced 3D-printed scaffolds: a stepwise countermeasure for osteosarcoma. Adv Mater 30: 1705611.
Citation: Zhu Y (2018) 3D Printing of Bioactive Ceramic Scaffolds for Bone Tissue Engineering. J Bioanal Biomed 10: e155. Doi: 10.4172/1948-593X.1000e155
Copyright: © 2018 Zhu Y. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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