Applications of Electrospun Drug-Eluting Nanofibers in Wound Healing: Current and Future Perspectives
Abstract
:1. Introduction
2. Process of Wound Healing
2.1. Hemostasis
2.2. Inflammation
2.3. Proliferation
2.4. Remodeling
3. Complications of Wound Healing
3.1. Factors Affecting Wound Healing
- Infection—Microbial colonization of the wound site is the most common barrier to wound healing. It is universally accepted that all wounds have some bacteria present on their surface; however, detrimental colonization of a host organism by foreign species defines wound infection [36]. Signs of wound infection generally present as a lack of friable granulation tissue, excessive exudate, and degraded wound beds, which are more or less a consequence of stimulation of inflammatory cells by invading bacteria [15].
- Necrosis—Necrosis is categorized by the presence of dead skin and foreign material at the wound site [15]. Necrotic cells are mortally harmed cells whose loss of function and cellular integrity could potentially evoke irritation in surrounding tissue, ultimately leading to a persistent inflammatory state and stalled wound healing [45].
- Nutrition—Wound healing involves several biological and molecular events that can be impaired by poor diet. Macronutrients like proteins, carbohydrates, and fats are necessary for the repair of lost tissue [46]. Inadequate dietary protein results in decreased wound tensile strength and a diminished ability of the body to defend the wound against infection. Furthermore, micronutrients such as vitamins and trace elements are essential components of cellular function and deficiencies in these molecules can impair the modulation of the healing phases [47].
- Moisture—Lack of moisture reduces tissue perfusion and slows down healing [15]. A moist environment is essential for the function of cells. Growth factors and other signalling molecules secreted following injury require a liquid medium for efficient intercellular communication. Epithelial cells also migrate and re-epithelialize more efficiently in a moist environment than in a dry one, saving tissue, time, and energy and reducing eschar formation [48].
- Individual physiologic variation–Patient conditions such as age and co-morbidities that restrict blood flow and hinder the activity of the immune system can cause non-healing of wounds [15]. Diabetes, obesity, hypothyroidism, and stress are associated with the development of chronic wounds. Conditions that present with impaired renal, hepatic, or respiratory function also hinder the wound healing process [33].
3.2. Wound and Scar Formation
4. Accelerating Healing of Surgical Wounds
“Class I/Clean: An uninfected operative wound in which no inflammation is encountered and the respiratory, alimentary, genital, or uninfected urinary tract is not entered. In addition, clean wounds are primarily closed and, if necessary, drained with closed drainage. Operative incisional wounds that follow nonpenetrating (blunt) trauma should be included in this category if they meet the criteria.
Class Il/Clean-Contaminated: An operative wound in which the respiratory, alimentary, genital, or urinary tracts are entered under controlled conditions and without unusual contamination. Specifically, operations involving the biliary tract, appendix, vagina, and oropharynx are included in this category, provided no evidence of infection or major break in technique is encountered.
Class Ill/Contaminated: Open, fresh, accidental wounds. In addition, operations with major breaks in sterile technique (e.g., open cardiac massage) or gross spillage from the gastrointestinal tract and incisions in which acute, nonpurulent inflammation is encountered are included in this category.
Class IV/Dirty-Infected: Old traumatic wounds with retained devitalized tissue and those that involve existing clinical infection or perforated viscera. This definition suggests that the organisms causing postoperative infection were present in the operative field before the operation.” [56].
4.1. Cell Therapy
4.2. Bioactive Therapeutic Delivery
4.3. Scaffolds/Biomaterials
Nanofibers
5. Drug-Eluting Fibers
5.1. Antibacterial Agents
5.2. Anti-Inflammatory Agents
5.3. Proliferation Enhancers
5.4. Factors Impeding Industrialization of Drug-Eluting Fibers
6. Economic Considerations
7. Future Perspectives and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Country | Overall Infection Rate * | SSI Detection (%) | Ref | |||
---|---|---|---|---|---|---|
a | b | c | x | |||
United States | 6.8 | 51.9 | 44.4 | 3.7 | [57] | |
United States | 16 | 78 | 9 | 13 | [58] | |
Hungary | 2.9 | 24 | 6 | 70 | [60] | |
Kosovo | 12 | 40.7 | 3.7 | 55.6 | [61] | |
Algeria | 5.4 | 62 | 38 | [62] | ||
Canada | 3.9 | 15.8 | 29.2 | 57.5 | [63] | |
United Kingdom | 15.6 | 14 | 86 | [64] | ||
Kosovo | 9.8 | 6.3 | 93.7 | [65] | ||
Saudi Arabia | 16.3 | 9 | 45 | 45 | [66] |
Therapeutic Agent/Class | Drug Carrier | Treatment Method | Therapeutic Activity Assessment Method | General Findings |
---|---|---|---|---|
Silver particles/antibacterial | Silver solution on 910 PGLA suture | Silver deposition technology | In vitro | Modified sutures demonstrated long-term antibacterial capability on Gram-positive and Gram-negative bacteria [113] |
Triclosan/antibacterial | Vicryl Plus ® (Ethicon, Cincinnati, Ohio, USA) | Coating | Double-blind randomized prospective pilot study | Toxic byproducts of triclosan possibly adversely affected wound healing [114] |
Chlorohexidine/Octenidine (antibacterial) | PA80/LA80 on Gunze PGA suture (Gunze Limited, Tokyo, Japan) | Dip coating | In vitro | Coated sutures were effective against multiple species within 48 h [115] |
Cefotaxime & Chitosan (antibacterial) | PLLA | Electrospinning (cefotaxime: core-sheath or blend), braiding and dipping in chitosan solution | In vitro | Constant drug release was observed for core-sheath. Mild tissue reactivity [104] |
Chitosan (antibacterial) | Braided silk sutures | Coating | In vitro | Increased knot strength of suture, both E. coli and S aureus were inhibited [116] |
Curcumin hydrochloride (antibacterial/anti-inflammatory) | PLLA | Electrospinning (curcumin hydrochloride blend) | Preclinical | Curcumin-loaded sutures exhibited superior mechanical strength. Optimized suture released the drug in a controlled manner. Improved antibacterial properties, marked antiplatelet performance, and good biocompatibility were observed [100] |
Ibuprofen (anti-inflammatory) | Braided polyglycolide thread/Poly(p-dioxanone) monofilaments | Coating | N/A | Drug release began with initial burst followed by then sustained release [117] |
Ibuprofen (anti-inflammatory) | PLGA sheets braided on VICRYL™W9114 suture (Ethicon, Cincinnati, Ohio, USA ) | Electrospinning (single/multiple layered sheets) | Preclinical | Drug loading was reproducible, multiple layers prolonged drug release. Pain relief efficacy similar to oral drug administration. Fabrication method is not scalable [105] |
Diclofenac (anti-inflammatory) | PLGA sheets braided on 3-0 VICRYL™W9114 suture (Ethicon, Cincinnati, Ohio, USA ) | Electrospinning | Preclinical | Sustained drug release was attained. Pain was mitigated throughout the wound healing period. Recruitment of inflammatory cells was suppressed [118]. |
VEGF (Proliferation enhancer) | PDLLA (VEGF blend) on Ethibond™ suture (Ethicon, Cincinnati, Ohio, USA ) | Coating | Preclinical | Meniscal healing did not improve, and angiogenesis did not increase [119] |
VEGF (Proliferation enhancer) | PLLA (VEGF blend) on EthiconPDS™ suture (Ethicon, Cincinnati, Ohio, USA ) | Coating | Preclinical | Biological activity and cellular viability increased [120] |
Norepinephrine/dopamine (bioadhesive) | Collagen-CaCO3 PNE composite scaffold | Electrospinning & complexation | In vitro | Satisfactory cellular adhesion, proliferation and differentiation of human fetal osteoblasts. Potential osteoconductive scaffolds for bone tissue engineering [121] |
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Akombaetwa, N.; Bwanga, A.; Makoni, P.A.; Witika, B.A. Applications of Electrospun Drug-Eluting Nanofibers in Wound Healing: Current and Future Perspectives. Polymers 2022, 14, 2931. https://doi.org/10.3390/polym14142931
Akombaetwa N, Bwanga A, Makoni PA, Witika BA. Applications of Electrospun Drug-Eluting Nanofibers in Wound Healing: Current and Future Perspectives. Polymers. 2022; 14(14):2931. https://doi.org/10.3390/polym14142931
Chicago/Turabian StyleAkombaetwa, Nakamwi, Alick Bwanga, Pedzisai Anotida Makoni, and Bwalya A. Witika. 2022. "Applications of Electrospun Drug-Eluting Nanofibers in Wound Healing: Current and Future Perspectives" Polymers 14, no. 14: 2931. https://doi.org/10.3390/polym14142931