Bone Tissue Engineering through 3D Bioprinting of Bioceramic Scaffolds: A Review and Update
Abstract
:1. Introduction
2. Bioceramic 3D Printing Overview
2.1. Biomaterials
2.2. Bioceramic Scaffolds
2.3. 3D Printing Manufacturing Technologies
2.3.1. Inkjet 3D Printing Technology
2.3.2. Selective Laser Sintering Technology
2.3.3. Direct-Ink-Writing 3D Printing Technology
2.3.4. SLA Printing Technology
2.3.5. Fused Deposition Modeling (FDM)
3. Improvements in 3D Printing Technology for Preparing Bioceramic Scaffolds
3.1. Improvements in Material Components
3.1.1. Carrying Active Ingredients
3.1.2. Doping with Trace Elements
3.1.3. Surface Functional Modification
3.2. Improvement in the Material Structure
3.2.1. Optimizing the Porous Structure
3.2.2. Construction of Micro-Nano Structures
3.2.3. Constructing a Bionic Structure
4. Conclusions and Prospects
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Types | Biomaterials | Advantages | Disadvantages | Composite Materials | In Vitro Study | In Vivo Study | Reference |
---|---|---|---|---|---|---|---|
Natural polymer materials | Chitosan | Excellent biocompatibility, osteogenic potential, compatibility, cytocompatibility. | Strong biodegradability, fast degradation speed, easy to deform | Chitosan-based SiO2 nanocomposites | Human osteoblasts (HOBs)s were used to detect cell adhesion and proliferation of scaffolds. | Scaffolds were implanted in nude mice to verify osteogenesis and vascularization. | [36,37] |
Alginate | Excellent biocompatibility, biodegradability, hydrophilicity, and low cost can be shaped. | Poor bioactivity, antioxidant, mechanical strength, and bone conductivity. | Alginate microbeads (AM) loaded with BMP-2. | Active expression of ALP in mesenchymal stem cells was used to examine the release of alginate microbeads carrier BMP-2. | Skull defect model rats and mice were injected subcutaneously to verify the higher osteogenic efficiency of alginate microbeads carrier BMP-2. | [38] | |
Collagen | Excellent biocompatibility and biodegradability; easily degrades and strong plasticity and low immunogenicity. | Fast degradation rate and poor mechanical properties | Mineralized collagen-hydroxyapatite-based scaffolds | Mouse calvarial 3T3 (MC3T3) cells were used to examine the in vitro cytocompatibility of various scaffolds. Osteogenic differentiation with fluorescent multi reporter mice BMSCs. | A mouse skull defect model was used to observe the bone regeneration ability of different scaffolds in vivo. | [39,40] | |
Artificial synthetic materials | Polylactic acid | Good biodegradability, biocompatibility, and processability; high mechanical strength. | Slow degradation rate, poor osteoconductivity. | Tantalum-coated polylactic acid fibrous membranes. | Preosteoblast cell lines (MC3T3-E1) were used to verify the biocompatibility of Ta-PLA electrospun membranes. | Rabbits with cylindrical skull defects were used to examine the osteogenic effect of Ta-PLA electrospun membranes. | [41] |
Polycaprolactone (PCL) | Good biocompatibility, biodegradability, and processability. | Poor bioactivity, Slow degradation rate, and long degradation cycle. | Polycaprolactone/ chitosan-g-polycaprolactone/hydroxyapatite electrospun nanocomposite scaffolds. | NIH 3T3 fibroblast cells and MG-63 cells were used to study the in vitro cytocompatibility of nanocomposite scaffolds. | PCL implantation in bone defect mice can promote bone defect repair with good cellular compatibility. | [42,35] |
Bioceramic Materials | Characteristic | Advantages | Disadvantages | Products | Reference |
---|---|---|---|---|---|
Alumina | Alumina is an inert ceramic material with good chemical stability and high mechanical strength. Abundant raw materials, low price, wide use, high mechanical strength, pressure resistance, high-temperature resistance, corrosion resistance, high-temperature insulation, and excellent dielectric properties. | Stability, biocompatibility, and excellent wear resistance, non-cytotoxic. | Limited strength, low mechanical properties. | Inert alumina ceramics, nanoporous alumina. | [47,48,49] |
Zirconia | Similar to inkjet 3D printing, a liquid binder is used to bind the powder together and then the support layer is printed layer by layer, finally, the powder printing stand is melted directly. High mechanical strength, high strength, high toughness, high hardness, excellent chemical corrosion and wear resistance, low thermal conductivity, good insulation, and self-lubrication. | Fracture resistance and flexural strength characteristics. | Micro-cracks or inducing a phase transformation (grind or sandblasting dental treatment), Chemical aging, and wear. | Yttria-stabilized tetragonal zirconia polycrystalline (Y-TZP), zirconias versus silica-based ceramics. | [50,51] |
Bioactive glass | Bioactive glass exhibits uniform interconnected macro-pores, high porosity, and high compressive strength. It can promote the expression of osteogenic genes in human bone marrow stromal cells. High biological activity, osteogenesis, osteoinduction, good combination with bone and soft tissue, and many functions. | Good bioactivity, biocompatibility, and no cytotoxicity promote bone and soft tissue regeneration. | Poor mechanical strength and intrinsic brittleness. | Bioactive glass ink; bioactive borosilicate glass (BG) scaffolds. | [52,53] |
Glass-ceramics | Glass-ceramics are mainly composed of ~70 vol % of interlocked rod-like lithium disilicate crystals with high compressive strength. High mechanical strength, adjustable thermal expansion, chemical corrosion resistance, and wide application. | It has sufficient strength and chemical stability, with outstanding aesthetics, transparency, as well as low thermal conductivity with adequate strength. In addition to biocompatibility, corrosion resistance, and chemical durability. | The production process is complicated and high cost. | Strontium doping glass-ceramic material, TiO2-containing glass-ceramics. | [54,55] |
Hydroxyapatite | Principal inorganic component of human or animal bones and teeth. | Good biocompatibility, bioactivity, and bone conductivity. | The degradation rate is slow, has a poor bone induction effect, and has high brittleness. | Hydroxyapatite coatings, poly (glycolic acid)/hydroxyapatite composite scaffolds. | [56,57,58] |
Calcium phosphates | Similar in composition to bone minerals, the most widely used synthetic bone substitutes. | Excellent biocompatibility, bioactivity, bone conductivity, and absorbability. | Low compressive strength, no toughness, slow degradation. | Beta-tricalcium phosphate (β-TCP)-based bioinks, 3D printed calcium phosphate cement (CPC). | [59,60,61] |
3D Printing Technologies | Principle | Advantages | Disadvantages | Reference |
---|---|---|---|---|
Inkjet 3D printing technology | The print head sprays an adhesive over a specific area to bind the powder material together, then accumulates layer by layer to form the final scaffold frame. | Low cost, a wide range of applications, printing does not require additional support. | The mechanical properties of the scaffold are low, the surface is very rough, and poor printing accuracy. | [9,10,11,12] |
Selective laser sintering technology | Similar to inkjet 3D printing, a liquid binder is used to bind the powder together and then the support layer is printed layer by layer, finally, the powder printing stand is melted directly. | No additional support is required, printed metal material. | High cost, low efficiency, the rough surface of the scaffold, low resolution, and long printing time. | [13,14,15] |
Ink direct writing 3D printing technology | The mobile print head directly extrudes the printing ink layer by layer to build a three-dimensional scaffold. | Fast printing speed, easy operation, low cost, good printing accuracy, widely used. | Low printing accuracy, additional support is needed to assist with printing, sag and deformation may occur. | [16,17,18] |
SLA printing technology | The 3D scaffold is printed layer by layer through photoinduced polymerization of photosensitive resin. | High accuracy allows printing of scaffolds with complex porous structures and very high resolution. | Need additional support, post-cleaning takes a lot of time and energy and affects roughness. | [19,20] |
Challenges | Solutions |
---|---|
Existing bioceramic scaffolds have insufficient toughness and are easy to fracture, so they cannot be used for bearing bones. | 3D printing technology and bionic technology to prepare composite multi-materials, with excellent mechanical properties of 3D-printed bioceramic scaffold. |
Clinical practice often requires the simultaneous treatment of the patient’s disease and repair of bone defects. | 3D printing technology combined with drug-carrying materials and bone growth-promoting factors has developed a 3D-printed multifunctional bioceramic scaffold that can be used for both disease treatment and tissue regeneration. The scaffolds can both treat disease and promote bone tissue regeneration. |
Existing 3D-printed bioceramics scaffolds are difficult to accurately mimic the highly complex and ordered microstructure of natural bone tissue. | Other micro-nano manufacturing technologies—such as hydrothermal processing, laser engraving, and electrospinning—are being combined with existing 3D printing technologies to produce scaffolds with finer structures. |
Existing 3D-printed bioceramic scaffolds cannot restore the full function of bone tissue. | Through the multi-channel 3D printing technology, a variety of materials and cells are combined to simulate the real situation of bone tissue in the body as much as possible. |
Existing 3D printing technology is difficult to be accurate to the nanometer scale, and can only be made into a scaffold and change its shape through physical and chemical methods. | The development of nano-scale 3D printing technology can prepare multi-tissue scaffolds with spatial and functional regulation. |
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Khalaf, A.T.; Wei, Y.; Wan, J.; Zhu, J.; Peng, Y.; Abdul Kadir, S.Y.; Zainol, J.; Oglah, Z.; Cheng, L.; Shi, Z. Bone Tissue Engineering through 3D Bioprinting of Bioceramic Scaffolds: A Review and Update. Life 2022, 12, 903. https://doi.org/10.3390/life12060903
Khalaf AT, Wei Y, Wan J, Zhu J, Peng Y, Abdul Kadir SY, Zainol J, Oglah Z, Cheng L, Shi Z. Bone Tissue Engineering through 3D Bioprinting of Bioceramic Scaffolds: A Review and Update. Life. 2022; 12(6):903. https://doi.org/10.3390/life12060903
Chicago/Turabian StyleKhalaf, Ahmad Taha, Yuanyuan Wei, Jun Wan, Jiang Zhu, Yu Peng, Samiah Yasmin Abdul Kadir, Jamaludin Zainol, Zahraa Oglah, Lijia Cheng, and Zheng Shi. 2022. "Bone Tissue Engineering through 3D Bioprinting of Bioceramic Scaffolds: A Review and Update" Life 12, no. 6: 903. https://doi.org/10.3390/life12060903