Prospects and Challenges of Electrospun Cell and Drug Delivery Vehicles to Correct Urethral Stricture
Abstract
:1. Introduction
2. Pathophysiology of US, Its Etiology, and Current Treatment Options
3. Pros and Cons of Potential Cell Sources to Repair Urethra Defects
4. Bioactive Agents That Can Prevent US
5. General Characteristics of Cell and Drug Delivery Systems to Treat Urethra Defects
Polymer/s. | Delivery System | Cell/Drug Type | Fabrication Method | Cell Type/s for In Vitro Study | In Vivo Model | Experimental Results | References |
---|---|---|---|---|---|---|---|
Polycaprolactone and fibrin | Hydrogel | Urothelial cells and smooth muscle cells | 3D printing | Urothelial cells and smooth muscle cells | - | The produced delivery system had comparable mechanical strength with rabbit urethra and supported cell viability up to 7 days after printing | [138] |
Propylene glycol | Hydrogel | Mitomycin C | Cross-linking | - | Clinical trial | Mitomycin C-loaded hydrogel could significantly reduce the recurrence of US after internal urethrotomy | [139] |
Gelatin methacrylate and pure collagen | Bioprinted scaffold | Bladder smooth muscle cells | Bioprinting | Bladder smooth muscle cells | - | Cells stayed viable in the printed scaffolds, and cell density increased over time | [140] |
Poly l lactic acid, poly D,L-lactic-co-glycolic acid, and poly(L-lactic acid-co-ε-caprolactone) | Porous sponge | Adipose-derived stem cells | Lyophilization | Adipose-derived stem cells | New Zealand white rabbit model of urethra defect | Hypoxia-preconditioned stem cells delivered via the porous scaffolds could successfully repair urethral defects and induced a robust angiogenesis | [141] |
Poly [N-isopropyl acry-lamide-co-n-butyl methacrylate] poly [NIPAAm-co-BMA]) and hydrophilic blocks (polyethylene glycol) | Hydrogel | Buccal epithelial cells | Sol-gel transition was obtained by changing the temperature. | Buccal epithelial cells | Clinical trial | The treated patients void well with a normal mean peak flow rate. Two of the six patients showed recurrent stricture at 18 and 24 months after treatment | [142] |
TGP | Hydrogel | Buccal mucosal epithelial cells | Thermo-reversible gelation | Buccal mucosal epithelial cells | Japanese white male rabbit model of urethra defect | Cells stayed viable in the hydrogel system and differentiated into fibroblast-like cells. Cell-loaded hydrogel system repaired urethra defects and cells engrafted at the injury site | [143] |
No materials were used | tubular scaffold | Human mesenchymal stem cells | Self-assembly | Human mesenchymal stem cells | Nude rat model | scaffolds showed two layers of cells and no stricture after implantation into the nude rat | [144] |
Natural ECM | Decellularized bladder matrices obtained from lamina propria | Autologous bladder epithelial and smooth muscle cells | Decellularization | Autologous bladder epithelial and smooth muscle cells | Rabbit model of anterior penile urethra defect | Cell-seeded tubular matrices showed a wide urethral caliber with no strictures. In addition, a transitional cell layer was formed in the cell-seeded matrix group, and the newly developed urethra showed contractility | [145] |
Silk fibroin and a nanoporous bacterial cellulose | Porous Bilayer scaffold | Lingual Keratinocytes and muscle cells | Freeze-drying and self-assembling | Lingual keratinocytes and muscle cells | Canine model of urethra defect | Microstructure studies showed that the seeded cells could adhere to the scaffolds. Cell-seeded urethral grafts showed superior healing function over cell-free ones | [146] |
Bacterial cellulose | 3D porous scaffold | Lingual keratinocytes | Biosynthesis via bacterial species | Lingual keratinocytes | New Zealand White male rabbit model of urethra defect | In scaffolds seeded with lingual keratinocytes, the caliber of the urethras was wide open and a continuous epithelium was formed | [147] |
Natural ECM | Decellularized human amniotic scaffolds | Allogeneic bone marrow mesenchymal cells and/or endothelial progenitor cells | Decellularization | Bone marrow mesenchymal cells and/or endothelial progenitor cells | Canine model of circumferential urethral defect | Animals treated with cell-seeded scaffolds showed unhindered urination and wide open urethra caliber. Furthermore, extensive vascularization was observed in this group | [60] |
Natural ECM | 3-D porous small intestinal submucosa | Urothelial and smooth muscle cells that were produced from the differentiation of urine-derived stem cells. | Decellularization | Urine-derived stem cells differentiated into urothelial cells and smooth muscle cells. | Cell-seeded scaffolds were implanted into Athymic mice | The seeded cells developed uniform layers on the scaffold and penetrated deep into the inner parts | [148] |
Poly-D,L-lactide-co-εcaprolactone | Bilayer polymeric matrix | Allogenic mesenchymal stem cells | Casting and air drying | Mesenchymal stem cells | Chinchilla rabbit model of urethra defect | Cell-seeded scaffolds showed integration with the urethra tissue with no adverse tissue reactions. Delivered cells expressed cytokeratin marker AE1/AE3, implying their potential differentiation into neo-urothelium | [149] |
Natural ECM | Acellular matrix | Endothelial progenitor cells that secrete antibiotic peptide LL37 | Decellularization | Endothelial progenitor cells | New Zealand white Male rabbit model of urethra defect | Antipoetic-delivering cells seeded on the acellular matrix could successfully repair critical-sized urethra defects | [150] |
Gelatin, poly l lactic acid, and silk fibroin | Porous tubular scaffolds | Mitomycin C and epidermal growth factor | Freeze drying | Urethral epithelial cells and urethral scar-derived fibroblast cells | - | The proportion of Urethral epithelial cells was significantly increased when cultured on the drug-loaded system | [151] |
Poly-l-lactic acid and poly-dl-lactic acid | Tubular scaffold | Paclitaxel | Casting | - | Male rabbit model of urethra defect | The drug-eluting stent could successfully prevent US, reduced inflammation, and alleviated fibrotic reactions | [152] |
Poly-L189 lactide-co-caprolactone (PLC) and Polyethylene glycol diacrylate (PEGDA) | Polyurethane double pig-tailed ureteric stent spray-coated with Mitomycin C-loaded PLC and overlaid with PEGDA hydrogel. | Mitomycin C | Spray coating and cross-linking | HBdSF cells | Porcine model | The developed system released the loaded drug sustainably and could deliver the drug to urothelium with no adverse effects | [153] |
Collagen | A synthetic catheter coated with collagen | Insulin-like growth factor 1 (IGF-1) | Coating on a synthetic catheter | HUEpCs cell line | Japanese white rabbit model of urethra defect | Animals treated with IGF-1/collagen-impregnated catheters had significantly bigger urethra caliber than other groups | [154] |
6. Principles of Electrospinning
7. Principles of Cell Delivery via Electrospun Scaffolds
8. Principles of Drug Delivery with Electrospun Scaffolds
9. Previous Applications of Electrospun Cell Delivery Systems to Treat Urethra Defects
10. Previous Applications of Drug-Loaded Electrospun Delivery Systems to Treat Urethral Defects
11. Challenges and Potential Mitigation Strategies
12. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameter | Effects | References |
---|---|---|
The molecular mass of the polymer | Polymers with low molecular mass tend to form beads, while higher molecular mass results in fibers with a more uniform structure | [161] |
Viscosity | The higher molecular mass and polymer concentration increase the viscosity of the polymeric solution. As a result, viscose solutions tend to produce thicker fibers | [162] |
Surface tension | Increasing the polymer concentration reduces the surface tension and leads to fibers with a continuous and uniform structure. Changing the solvent system or adding surfactant can also alter surface tension | [163] |
Conductivity | The polymeric solution’s conductivity affects the fibers’ mean fiber size and morphology. Incorporation of salts or polyelectrolytes can improve conductivity | [164] |
Applied voltage | High voltages decrease the average fiber diameter. Furthermore, high voltages stretch the fibers and align the polymeric chains, increasing fibers’ crystallinity | [165] |
Solution flow rate | The average fiber diameter will increase with higher flow rates and vice versa | [166] |
Needle to collector distance | The increase in the fiber receiving distance to a certain extent will produce ultrafine fibers. Therefore, the distance should be optimized for every polymeric solution; otherwise, disintegrated or beady fibers will be produced | [167] |
Properties of the receiver | The architecture and morphology of the fibers can be determined by using different collectors. Increasing the collector’s rotation rate increases the alignment of fibers. In addition, 3D electrospun matrices can be produced when fibers are spun into a liquid coagulation bath | [168,169] |
Humidity | Humidity can alter the solvent’s humidity and cause fibers’ fusion | [170] |
Temperature | Temperature can alter viscosity, solvents’ volatility, and surface tension. In addition, high-temperature results in rapid solvent evaporation and reduces the flying time, thereby increasing fibers’ diameter | [171] |
Air pressure | The air pressure affects the solvent’s volatility and jet stability. However, fibers with a uniform structure and consistency can be produced when spun at a constant air pressure | [172] |
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Farzamfar, S.; Elia, E.; Chabaud, S.; Naji, M.; Bolduc, S. Prospects and Challenges of Electrospun Cell and Drug Delivery Vehicles to Correct Urethral Stricture. Int. J. Mol. Sci. 2022, 23, 10519. https://doi.org/10.3390/ijms231810519
Farzamfar S, Elia E, Chabaud S, Naji M, Bolduc S. Prospects and Challenges of Electrospun Cell and Drug Delivery Vehicles to Correct Urethral Stricture. International Journal of Molecular Sciences. 2022; 23(18):10519. https://doi.org/10.3390/ijms231810519
Chicago/Turabian StyleFarzamfar, Saeed, Elissa Elia, Stéphane Chabaud, Mohammad Naji, and Stéphane Bolduc. 2022. "Prospects and Challenges of Electrospun Cell and Drug Delivery Vehicles to Correct Urethral Stricture" International Journal of Molecular Sciences 23, no. 18: 10519. https://doi.org/10.3390/ijms231810519