Therapeutic Agent-Loaded Fibrous Scaffolds for Biomedical Applications
Abstract
:1. Introduction
2. Natural Materials for Fibrous Scaffolds
2.1. Polysaccharides
2.1.1. Alginate
2.1.2. Chitosan
2.1.3. Hyaluronic Acid
2.2. Proteins
2.2.1. Collagen
2.2.2. Silk Fibroin
2.2.3. Elastin
3. Fabrication Methods
3.1. Electrospinning
3.1.1. Bicomponent Spinning
3.1.2. Coaxial Electrospinning
3.1.3. Multijet Electrospinning
3.1.4. Emulsion Electrospinning
3.2. Three-Dimensional Printing
3.2.1. Fused Deposition Modeling
3.2.2. Stereolithography
3.2.3. Selective Laser Sintering
3.2.4. Selective Laser Melting
3.3. Microfluidics
3.3.1. Principle of the Microfluidic Synthesis of Fiber
3.3.2. Microfluidic Devices
3.4. Solution Blowing
3.5. Centrifugal Spinning
4. Drug-Loading Methods
4.1. Blending
4.2. Chemical Immobilization
4.3. Physical Adsorption
4.4. Emulsion Electrospinning
4.5. Coaxial Electrospinning
4.6. Electrospray Technology
5. Biomedical Applications of the Therapeutic Agent-Loaded Fibrous Scaffolds
5.1. Scaffolds for Cardiovascular Regeneration and Vascularization
5.2. Regenerating Agent-Loaded Fibrous Scaffolds for Nerve Regeneration
5.3. Bone Regeneration
5.4. Scaffolds for Wound Healing
5.5. Anticancer Drug-Loaded Fibrous Scaffolds for Inhibiting the Recurrence and Metastasis of Cancer
5.6. Additional Therapeutic Applications of the Fibrous Scaffolds
6. Future Perspective and Limitations
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Spinning Method | Key Features | Applications |
---|---|---|
Bicomponent spinning [79,80] | Two polymers are spun together to create a core–sheath or side-by-side structure | Medical textiles, filtration, and protective clothing |
Coaxial electrospinning [81,82,83] | Two or more fluids are spun together in a coaxial arrangement, producing fibers with a core–shell structure | Drug delivery, tissue engineering, and energy storage |
Multijet electrospinning [83,84,85] | Multiple spinning nozzles are used simultaneously to produce a large volume of fibers in a short amount of time | Tissue engineering, drug delivery, and energy storage |
Emulsion electrospinning [86,87,88] | An emulsion of two immiscible liquids is spun to create fibers with a polymer and a liquid core | Drug delivery, tissue engineering, and food packaging |
Methods | Principles | Materials Used | Advantages | Disadvantages |
---|---|---|---|---|
Fused deposition modeling [89,90] | Thermoplastic filaments are melted and deposited layer by layer using a heated nozzle | ABS, PLA, Nylon, TPU, etc. | Low cost, user-friendly, wide material compatibility, good for prototyping | Lower resolution, visible layer lines, limited to certain geometries, weaker mechanical properties |
Stereolithography (SLA) [91,92] | Uses a UV laser to selectively cure a liquid photopolymer resin layer by layer | Resin materials (acrylic, epoxy, polyurethane, etc.) | High resolution, good surface finish, suitable for small and intricate parts, good for prototyping and production | Limited material selection, expensive, post-processing required, not suitable for large parts |
Selective laser sintering (SLS) [93,94,95] | Uses a laser to selectively fuse a powdered material (such as nylon) layer by layer | Nylon, TPU, polycarbonate, etc. | No support structures required, can produce complex geometries, good mechanical properties, good for low-volume production | Limited surface finish, expensive, post-processing required, not suitable for small parts |
Selective laser melting [96] | Similar to SLS, but uses a laser to fully melt the powdered material instead of just fusing it, resulting in fully dense metal parts | Metals such as titanium, aluminum, steel, etc. | High strength, good for small and complex parts, wide range of materials available | Expensive, limited build size, slow printing speed, post-processing required |
Fabrication Methods | Parameters | Considerations |
---|---|---|
Electrospinning [119,120,121] | Solution viscosity | Higher viscosity results in larger polymer beads and thicker fibers |
Solution conductivity | Higher conductivity improves the quality of fibers | |
Applied voltage | Higher voltage results in thinner fibers | |
Distance between the collector and the needle | Shorter distance results in denser fibers | |
Flow rate of the solution | Higher flow rate leads to larger fiber diameter | |
Needle diameter | Smaller diameter results in thinner fibers | |
Solution concentration | Higher concentration results in thicker fibers | |
Humidity and temperature of the environment | Affects fiber morphology and diameter | |
3D Printing [89,90,91,92,93,94,95,96] | Material properties | Affects printability and mechanical properties |
Printing speed | Affects print quality and resolution | |
Layer height | Affects resolution and mechanical properties | |
Temperature of the printing environment | Affects material properties and print quality | |
Extruder speed | Affects flow rate and print quality | |
Nozzle diameter | Affects resolution and print speed | |
Printing bed temperature | Affects adhesion and warping | |
Printing orientation | Affects mechanical properties | |
Microfluidic method [100,106,107,108,109,110,111] | Flow rate of the fluid | Affects fiber diameter and porosity |
Viscosity of the fluid | Affects flow rate and fiber morphology | |
Channel geometry | Affects fiber diameter and alignment | |
Material properties | Affects fiber morphology and mechanical properties | |
Surface properties | Affects fiber adhesion | |
Temperature and pressure of the system | Affects fiber morphology and diameter | |
Solution blowing [113,114,115] | Solution viscosity | Higher viscosity results in thicker fibers |
Gas flow rate | Affects fiber diameter and morphology | |
Distance between the nozzle and the collector | Affects fiber alignment and density | |
Solution concentration | Higher concentration results in thicker fibers | |
Temperature and humidity of the environment | Affects fiber morphology and diameter | |
Centrifugal spinning [116,117,118] | Polymer concentration | Higher concentration results in thicker fibers |
Centrifugal force | Affects fiber diameter and alignment | |
Distance between the collector and the nozzle | Affects fiber alignment and density | |
Solution viscosity | Higher viscosity results in thicker fibers | |
Solution flow rate | Affects fiber diameter and morphology | |
Polymer molecular weight | Affects mechanical properties | |
Temperature and humidity of the environment | Affects fiber morphology and diameter |
Method | Parameters | Considerations |
---|---|---|
Blending [122,123,124,125,126,127] | Solubility of drug and polymer | Drug and polymer should have similar solubilities |
Drug and polymer concentration | Higher concentrations lead to higher drug loading | |
Mixing time and speed | Affects drug–polymer interaction and drug distribution | |
Chemical immobilization [128,129] | Type of chemical reaction | Reaction should be specific to the drug and polymer |
Concentration of reactants | Higher concentrations lead to higher drug loading | |
Reaction time and temperature | Affects the efficiency of the reaction and drug loading | |
Physical adsorption [130,131,132] | Surface area of the scaffold | Larger surface area leads to higher drug loading |
Solution concentration and pH | Affects drug–polymer interaction and adsorption efficiency | |
Adsorption time and temperature | Affects the efficiency of drug adsorption | |
Emulsion electrospinning [133,134,135] | Polymer and drug solubility | Solubility should be matched for codissolving |
Emulsifier concentration | Affects droplet size and stability | |
Electrospinning parameters | Affects fiber diameter and drug distribution | |
Emulsion stability | Emulsion should be stable for efficient drug loading | |
Coaxial electrospinning [137,138,139] | Core and shell polymer solubility | Solubility should be matched for codissolving |
Core and shell polymer concentration | Higher concentrations lead to higher drug loading | |
Coaxial electrospinning parameters | Affects fiber diameter, shell thickness, and drug distribution | |
Core–shell fiber stability | Core and shell should remain stable during processing | |
Electrospray [140,141] | Solution concentration and pH | Affects drug–polymer interaction and encapsulation efficiency |
Flow rate and voltage | Affects droplet size and drug distribution | |
Solvent type | Affects the solubility of the drug and polymer | |
Post-processing conditions | Can affect drug loading and release kinetics |
Biomedical Applications | Fabrication Methods of Scaffold | Therapeutic Agent (with its Function) | Drug-Loading Methods | References |
---|---|---|---|---|
Cardiovascular regeneration | Electrospinning method | α-Mangostin (antioxidant, cardioprotective activity) | Dip coating | [144] |
Cardiovascular regeneration | Electrospinning method with crystallization | Heparin (antithrombosis activity) | Drug-mixing (blending) electrospinning method | [151] |
Vascular regeneration | Coelectrospinning method | IL-4 (immune modulation for vascular stabilization) | Surface modification of the scaffold | [239] |
Cardiac regeneration | Electrospinning method | Resveratrol (inducing cardioprotective effect) | Drug-mixing electrospinning method | [240] |
Nerve regeneration | Electrospinning method | MicroRNAs (miRNAs, genetic modulation for nerve regeneration) | Passive loading after scaffold fabrication | [167] |
Nerve regeneration | Electrospinning method with rolling | Deferoxamine (promoting angiogenesis with anti-inflammation) | Drug-mixing electrospinning method | [169] |
Nerve regeneration | Microsol electrospinning | IL-4 encoding plasmid DNA (IL-4 generation for immune suppression) | Chemical modification of pDNA-loaded liposome | [176] |
Nerve regeneration | Electrospinning method | Magnetic nanoparticles (MgO, inhibiting nerve cell apoptosis), purmorphamine and retinoic acid (Pur/RA, inducing neuronal differentiation) | Pur/RA-loaded MgO-mixing electrospinning method | [241] |
Nerve regeneration | Electrospinning method | Acidic fibroblast growth factor (aFGF, signaling molecule for axon growth) | Coaxial electrospraying of aFGF-loaded nanoparticles | [242] |
Nerve regeneration | Microsol electrospinning method | Brain-derived neurotrophic factor (BDNF, improving differentiation of bone marrow mesenchymal stem cells into neurons) | Drug-mixing electrospinning method | [243] |
Bone regeneration | 3D printing with TIPS technique | Deferoxamine (DFO, inducing angiogenesis for vascularization) | Passive drug loading after scaffold fabrication | [182] |
Bone regeneration | Coaxial electrospinning method | DFO (inducing vascularization), dexamethasone (DEX, modulating osteogenic differentiation) | Drug-mixing electrospinning method | [15] |
Bone regeneration | Electrospinning method | Vascular endothelial growth factor (VEGF) encoding pDNA (inducing vascularization), bone morphogenetic protein 2 (BMP2, promoting growth of bone tissue) | Surface immobilization of drug-loaded vector and embedding drug containing hydrogel inside the scaffold | [186] |
Bone regeneration | Electrospinning method | Tannic acid (TA) and indomethacin (IND) (agents for anti-inflammation) | TA/IND nanomedicine-mixing electrospinning method | [190] |
Bone regeneration | Coaxial electrospinning method | Tauroursodeoxycholic acid (TUDCA, inducing vascularization), BMP2 (promoting growth of bone tissue) | Drug-mixing electrospinning method | [244] |
Bone regeneration | Electrospinning method | Recombinant human vein endothelial growth factor (rhVEGF, inducing vascularization), recombinant human bone morphogenetic protein 2 (rhBMP2), and calcium phosphates (inducing bone tissue regeneration) | Drug-mixing electrospinning method | [245] |
Bone regeneration | Electrospinning method with crosslinking | IL-4 (immunomodulation for vascular maturation and osteogenesis) | Drug-mixing electrospinning method | [246] |
Wound healing | Electrospinning method | Vitamin K3 carnosine peptide (agent for antibacterial activity) | Drug-mixing electrospinning method | [198] |
Wound healing | Microsol electrospinning method | IL-10 (agents for anti-inflammatory effect) | Drug-mixing electrospinning method | [210] |
Wound healing | Electrospinning method | Nitric oxide (NO, agent for antibacterial activity) | Surface modification after scaffold fabrication | [214] |
Wound healing | Electrospinning method | Cordia myxa (agent for antibacterial activity with antioxidant effect) | Immobilization after scaffold fabrication | [247] |
Wound healing | Electrospinning method | Anemoside B4 (ANE, agent for anti-inflammation) | Incorporation of ANE after scaffold fabrication | [248] |
Wound healing | 3D printing | Vascular endothelial growth factor (VEGF, inducing vascularization), gentamicin (antibiotic agent), silver nanoparticle (antibacterial agent) | Drug loading in 3D printing ink | [249] |
Wound healing | Physical coassembling to construct fibrous hydrogel | Phycocyanin (anti-inflammatory activity), gallic acid (antibacterial activity and anti-inflammatory activity) | Mixing drugs for assembled fibrous scaffold fabrication | [250] |
Wound healing | Electrospinning method | Manganese dioxide (MnO2, agent for assuaging oxidative stress), curcumin (agent for anti-inflammation) | Curcumin-loaded MnO2 nanoparticle-mixing electrospinning method | [251] |
Wound healing | Electrospinning method | Pyrogallol and saikosaponin (reducing reactive oxygen species (ROS)) | Drug-mixing electrospinning method | [252] |
Wound healing | Electrospinning method | Curcumin (agent for anti-inflammation), cerium nitrate (reducing ROS for antiscar wound healing) | Drug-mixing electrospinning method | [253] |
Wound healing | Layer by layer electrospinning method | Silver (I) sulfadiazine (agent for antibacterial activity) | Drug-mixing electrospinning method | [254] |
Tumor inhibition | 3D printing with electrospinning method for multiple-layered scaffold fabrication | Combretastin A4 (CA4, inhibiting tumor growth) and doxorubicin (DOX, inhibiting metastasis and recurrence of cancer) | DOX: drug-mixing electrospinning method, CA4: drug-mixing in bioink before 3D printing | [225] |
Tumor inhibition with antibacterial activity | Electrospinning method | Gemicitabine (GEM, inhibits tumor growth), silver nanoparticle (antibacterial agent for enhancing tumor therapy) | GEM: drug mixing electrospinning method, silver nanoparticle: dipping process after scaffold fabrication with coating | [228] |
Tumor inhibition | Sol–gel process with electrospinning method | Glucose oxidase (GOx, inducing starvation activity around tumor tissue), hyaluronidase (HAase, destroying tumor extracellular matrix (ECM) to penetrate nanomedicine), banoxantrone (AQ4N, antitumor agent) | Incorporation of HAase and GOx/AQ4N-loaded nanoparticles after scaffold fabrication | [255] |
Tumor inhibition | Coaxial 3D printing | DOX (antitumor agent), polydopamine (photothermal agent for thermal-induced tumor therapy) | Mixing drugs in ink and fabricating scaffold | [256] |
Tumor inhibition with wound healing | Coaxial electrospinning method | Fluorouracil (5-FU, agent for chemotherapy of melanoma) | 5-FU-loaded nanoparticle-mixing electrospinning method | [257] |
Periodontal regeneration | Electrospinning method | Dimethyloxalylglycine (DMOG, inhibitor of prolyl hydroxylases to promote VEGF) | Drug-mixing electrospinning method | [231] |
Tendon regeneration | Electrospinning method | Nitric oxide (NO, agent for vascularization) | Use of NO-loaded metal–organic framework-mixing electrospinning method | [237] |
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Park, D.; Lee, S.J.; Choi, D.K.; Park, J.-W. Therapeutic Agent-Loaded Fibrous Scaffolds for Biomedical Applications. Pharmaceutics 2023, 15, 1522. https://doi.org/10.3390/pharmaceutics15051522
Park D, Lee SJ, Choi DK, Park J-W. Therapeutic Agent-Loaded Fibrous Scaffolds for Biomedical Applications. Pharmaceutics. 2023; 15(5):1522. https://doi.org/10.3390/pharmaceutics15051522
Chicago/Turabian StylePark, Dongsik, Su Jin Lee, Dong Kyu Choi, and Jee-Woong Park. 2023. "Therapeutic Agent-Loaded Fibrous Scaffolds for Biomedical Applications" Pharmaceutics 15, no. 5: 1522. https://doi.org/10.3390/pharmaceutics15051522