A Review of Biomaterials and Scaffold Fabrication for Organ-on-a-Chip (OOAC) Systems
Abstract
:1. Introduction
2. Scaffold Requirements
2.1. Biocompatibility
2.2. Biodegradability
2.3. Mechanical Properties
2.4. Scaffold Architecture
2.5. Manufacturing Technology
2.6. Scaffold Integration in OOAC System
2.6.1. Hydrogels
2.6.2. Additive Manufacturing Derived Scaffolding
3. Biomaterials
3.1. Naturally-Derived Materials
3.1.1. Matrigel
3.1.2. Collagen
3.1.3. Chitosan
3.1.4. Alginate
3.1.5. Cellulose
3.1.6. Gelatin
3.2. Synthetically Derived Materials
3.2.1. Poly-(Ɛ-caprolactone)—PCL
3.2.2. Poly-(dimethyl-siloxane)—PDMS
3.2.3. Polylactic Acid—PLA
3.2.4. Polyethhene Glycol—PEG
3.2.5. Polyglycolic Acid—PGA
3.2.6. Polyurethane—PU
3.3. Materials Overview
4. Manufacturing Techniques
4.1. Electrospinning
4.2. Three-Dimensional (3D) Printing
4.2.1. Stereolithography (SLA)
4.2.2. Fused Deposition Modelling (FDM)
4.2.3. Selective Laser Sintering (SLS)
4.2.4. Bioplotting/Bioprinting
4.3. Salt-Leaching
4.4. Phase Separation
4.5. Freeze Drying
4.6. Manufacturing Overview
5. Discussion
6. Conclusions
- To move from animal-derived products, further research and development using synthetically derived products are required to achieve the same quality and reproducibility of data. The use of RGD or similar anchoring proteins increases cell viability in the tissue, enhancing the properties of synthetic materials.
- Manufacturing techniques can be used to manipulate scaffold properties according to the requirements of the specific tissue making them dynamically tunable. Combining different techniques and using the right materials is the key to OOAC scaffold standardisation.
- Current OOAC systems use their version of scaffolds, which makes data hard to compare across research groups. This presents a major obstacle to the use of these devices as pre-clinical models since they are not regulated. Hence, the creation of Standards approved by entities such as the European Centre for the Validation of Alternative Methods (ECVAM) is crucial for the approval of these systems as validated models. Researchers from both academia and industry in collaboration with regulators could use standards such as ISO/TS 21560:2020 (general requirements of tissue engineering medical products) as a starting point to close the gap in regulation within the OOAC research field.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Material | Advantages | Disadvantages | Examples of OOAC | References |
---|---|---|---|---|
Matrigel | Promotes cell adherence. Extremely biocompatible. Similar mechanical properties as natural ECM. | Batch to batch composition variability may affect results. | Liver-on-a-Chip | [10,15,16,80,81,82,83,85,86,89] |
Collagen | Most predominant protein in mammals’ ECM. Controls morphology, adhesion, and differentiation. Good permeability. | Lacks mechanical strength and structural stability when hydrated. | Gut-on-a-Chip | [90,91,92,93,94,95,96,98,99,101,102] |
Chitosan | Biocompatible. Biodegradable. Permeation enhanced. | Mechanically week and unstable. | Vascular microfluidic device | [103,104,105,106,107,108,109] |
Alginate | Reduced production cost. Mechanical Strength can be adjusted depending on molecular weight. | Purity will affect biocompatibility. It will not naturally degrade in mammal derived tissues. Poor cell adhesion. | Microfluidic devices using cardiac tissue, liver and hepatocytes. | [111,112,113,114,115,116,117,118,120,121,122,123] |
Cellulose | Insoluble in water. High mechanical strength. Allows water retention. Biocompatible. Optical transparent. | Degraded by microbial and fungal enzymatic activity. | Microfluidic device using lung cancer cells. | [124,125,126,127,129,130,131,132] |
Gelatin | Biocompatible. Biodegradable. Good water-solubility. Low cost. | Animal-derived. | Microfluidic devices emulating vascular environments. | [134,135,136,137,139,140,141] |
Poly-(Ɛ-caprolactone)—PCL | Low cost. Compatible with many manufacturing techniques. Good mechanical properties. | Slow biodegradability rate. | Microfluidic devices to emulate the myocardium and vascular environments. | [142,143,144,145,146,147,148,149,150,151,152,153] |
Poly-(dimethyl-siloxane)—PDMS | Biocompatible. Optical transparent. High flexibility adequate for cyclic stretching. | Non-degradable. Hydrophobic. Absorbs small molecules. | Lung-on-a-Chip Kidney-on-a-Chip Brain-on-a-Chip | [7,13,154,155,156,157,158,159,160,161,162,163,164,165] |
Polylactic Acid—PLA | Biodegradable. Mechanical properties are tunable. | Not suitable for OOAC systems with high mechanical strain. | Cell culture chips with MSCs | [49,166,167,168,169,170,171] |
Polyglycolic Acid—PGA | Biodegradable. Biocompatible. | High degradation rate. | 3D cultures of autologous smooth muscle and urothelium | [179,180,181,182,183,184,185,186] |
Poly(lactide-co-glycolide)—PLGA | Biodegradable. Biocompatible. High Porosity. High Mechanical Strength. | High degradation rate. | Lung-on-a-Chip Blood-Brain Barrier Vascular Network Scaffold | [37,42,152,184,191,192] |
Polyurethane—PU | Hydrophilic. Biocompatible. Biodegradable. Compatible with many manufacturing techniques. | Lung-on-a-Chip | [187,188,189] |
Manufacturing Technique | Advantages | Disadvantages | Examples of Scaffolds Produced | Pore Size | References |
---|---|---|---|---|---|
Electrospinning | High surface area. High porosity. Simple and inexpensive solutions can be used. Wide range of polymers. | Toxic organic solvents are used. | PCL | ~3–5 μm. | [22,195,196,197,199,200,201,202] |
Gelatin | |||||
PCL/Collagen Chitosan | |||||
SLA | Controlled resolution. | Final resolution may be compromised by shrinkage in colling process. | PCL | 25–100 μm. | [22,204,205,206] |
Calcium phosphate (CaeP)/poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV) | |||||
FDM | Precise deposition of thin layers of polymers. | Elevated temperature that limits material choice. | PCL | 100–300 μm. | [22,209,210,211,212] |
SLS | Fast and cost-effective. Does not require the use of organic solvents. | Elevated temperature requires high energy input. Degradation of the material may occur. | PCL | Minimum around 400 μm. | [216,217,221,222,247] |
Poly(ethylene glycol)/poly(D,L-Lactide) hydrogel | |||||
Bioplotting | High resolution for an extrusion system. Various materials can be used during the print. | Limited geometry designing. High-cost technology. | Poly(lactides) PCL Poly(lactide-co-glycolide) Chitosan | [35,223,224,225,226] | |
Gelatin | |||||
Salt-leaching | Small amount of polymer needed. Does not require large machinery. Low-cost. | Interpore opening and pore size are not controllable. | Sodium Chloride as porogen. | Up to 500 μm, dependent on porogen size. | [230,231,232,233,234] |
Phase Separation | Harsh chemical solvents are not needed. Lower fabrication time. | Use of organic solvents (e.g., ethanol or methanol) inhibits incorporation of bioactive molecules. Small pores. | Gelatin/silica hydrogels. | ~100 μm Depends on porogen size. | [22,187,235,236,237] |
Freeze Drying | No rinsing steps. | Reduced heterogeneous freezing may occur. | PLGA | ~85–325 μm. | [192,237,239,240,241,242,243] |
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Osório, L.A.; Silva, E.; Mackay, R.E. A Review of Biomaterials and Scaffold Fabrication for Organ-on-a-Chip (OOAC) Systems. Bioengineering 2021, 8, 113. https://doi.org/10.3390/bioengineering8080113
Osório LA, Silva E, Mackay RE. A Review of Biomaterials and Scaffold Fabrication for Organ-on-a-Chip (OOAC) Systems. Bioengineering. 2021; 8(8):113. https://doi.org/10.3390/bioengineering8080113
Chicago/Turabian StyleOsório, Luana A., Elisabete Silva, and Ruth E. Mackay. 2021. "A Review of Biomaterials and Scaffold Fabrication for Organ-on-a-Chip (OOAC) Systems" Bioengineering 8, no. 8: 113. https://doi.org/10.3390/bioengineering8080113