Smart Wound Dressings for Diabetic Chronic Wounds
Abstract
:1. Background
2. Chronic Inflammation in Diabetic Wounds
3. Current Treatment and Challenges
4. Current Wound Dressings
4.1. Natural Polymers
4.1.1. Cellulose
4.1.2. Chitosan
4.1.3. Collagen and Gelatin
4.1.4. Hyaluronic Acid
4.2. Synthetic Polymers
4.2.1. Poly(lactide-co-glycolide)
4.2.2. Polyurethanes
4.2.3. Polyethylene Glycol
4.2.4. Polycaprolactone
4.3. Smart Polymers
4.4. Fiber Geometry and Scaffold Architecture
5. Biosensing in the Chronic Wound Environment
5.1. Biomarkers for Wound Healing
5.1.1. Biochemical Markers
5.1.2. Physical Biomarkers
5.2. Biochemical Sensors
5.2.1. Matrix Metalloproteinases
5.2.2. Uric Acid
5.2.3. pH
5.2.4. Bacterial
5.2.5. Nitric Oxide
5.2.6. Oxygen
5.3. Physical Sensors
5.3.1. Impedance
5.3.2. Temperature Sensors
5.3.3. Integrated Sensors
6. Sensor Clinical Outcomes
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Wagner-Meggitt | University of Texas | PEDIS | |
---|---|---|---|
Grade 0 | Pain only, no open ulcer | Pre-ulceration | |
Grade 1 | Superficial ulcer | Superficial wound | Skin intact, no infection or loss of sensation |
Grade 2 | Deep ulcer | Wound penetrating to tendon or capsule | Superficial ulcer with infection at the surface and loss of sensation |
Grade 3 | Deep ulceration with osteomyelitis | Wound penetrating to bone or joint | Ulcer reaching the fascia, muscle, and tendon, fasciitis and septic arthritis likely |
Grade 4 | Localized Gangrene | Ulcer depth reaching the bone or joint, SIRS | |
Grade 5 | Extensive Gangrene, Amputation likely | ||
References | [13,16,17] | [18] | [19] |
Polymer | Advantages | Disadvantages | Reference |
---|---|---|---|
Cellulose | 1. Readily available with low cost 2. Fiber and foam materials 3. Creates a gel-like material, forming a moist environment 4. Releases GFs to stimulate fibroblast proliferation | 1. Requires additional antimicrobial substances 2. Resorption in tissues does not occur, which could cause further tissue damage or become overwhelmed by excess exudate | [36] |
Chitosan | 1. Fabricated in a gelatin of film-like material 2. Antimicrobial and hemostatic properties 3. Functional derivatives allowing for modified and versatile effects 4. Ability to deliver drugs | 1. Extensive swelling in water 2. Unable to dissolve in organic solvents because of its rigid crystalline structure | [38,43,44,45,70,71] |
Collagen and Gelatin | 1. Promotes tissue granulation and angiogenesis 2. Inhibits bacterial growth and prolonged inflammatory response 3. Gelatin derivative forming a hydrogel material | 1. May not be absorptive in gelatin form, especially for wounds with excessive exudate 2. Might require secondary dressing | [22,38,46,48] |
Hyaluronic Acid | 1. Lubricative and water absorptive 2. Bi-products promote epithelial cell migration 3. Improves collagen deposition and angiogenesis4. Popular drug delivery system and vehicle for growth factors | 1. Only MMWHA enhances wound repair | [52,72,73,74] |
Poly(lactide-co-glycolide) | 1. FDA approved for drug delivery, suture applications 2. Ratio of lactide to glycolide units can modify release of drugs and growth factors 3. Cytocompatible and stimulates fibroblast adhesion, spreading, and proliferation 4. Fabricated into various shapes | 1. Requires additional antimicrobial substances 2. Properties fail to match ECM or collagen | [38,56,57,58,59] |
Polyurethanes | 1. Semipermeable membrane that prevents bacteria from entering 2. Provides a moist environment 3. Delivers bioactive substances for fighting infection 4. Drainage properties that decrease the risk of swelling | 1. Need composite dressings in order to provide contact layer and waterproof properties 2. Wound healing effects are only associated with nanofiber structure | [57,61,62] |
Poly(ethylene glycol) | 1. Hydrophilic, flexible and compatible qualities 2. Surface modifier allowing for better grip in the contact layer 3. Growth factors have higher affinity for PEG | 1. Adhesiveness might damage granulation tissue 2. Does not incorporate antibiotics and other drugs so composite materials are needed | [38,57,64] |
Polycaprolactone | 1. FDA approved for suture applications 2. Fibrous structure similar to ECM architecture 3. Water retention capacities used to capture wound exudate 4. Resistant to many solvents allowing for slow and controlled degradation | 1. Lack of antimicrobial properties | [67,68,69] |
Biochemical Biomarkers | ||
Wound Biomarker | Significance in Chronic Wounds vs. Acute Wounds | Reference |
Cytokines (IL-1, IL-6, TNF-α) | Elevated levels of Cytokine | [11,90] |
Nitric Oxide | Decreased levels of NO | [89,93] |
Matrix Metalloproteinase | Increased protease activity | [11,91] |
Oxygen | Higher probability for ischemia due to decreased oxygen levels | [9] |
Bacteria | Bacteria concentration levels are higher indicating extent of infection. | [9,92] |
Wound pH | Remains more alkalotic for extended period of time | [86] |
Uric Acid | Decreased levels due to bacteria | [94] |
Reactive Oxygen Species | Increased levels due to oxidative stress | [11] |
Gene Expression | Increase in bacterial housekeeping genes; decrease in ulcer housekeeping genes. | [11] |
Growth Factors | Decreased level (i.e., PDGF) | [11] |
Physical Biomarkers | ||
Wound Biomarker | Significance in Chronic Wounds vs. Acute Wounds | Reference |
Bioelectrical Impedance | Phase angle, resistance, and reactance are all decreased | [87] |
Pressure | Increased pressure | [95] |
Temperature | Increased temperature | [96] |
Sensor | Sensitivity/Range | Biomarker | Method | Reference |
---|---|---|---|---|
ELISA MMP Sensor | 0.1–100 mg/mL | MMP-9 | Electrochemical | [99] |
Disposable MMP-9 Sensor | 200 mg/mL | MMP-9 | Electrochemical Impedance Spectroscopy | [90] |
Smart Bandage UA Sensor | 100 µM of UA | Uric Acid | Electrochemical | [94] |
Carbon fiber sensor | 0–500 µM | Uric Acid | Electrochemical | [100] |
Wearable enzymatic sensor | 0.14 µ/M-cm2 Range: 14 µM | Uric Acid | Electrochemical | [101] |
Poly-tryptophan Carbon Fiber pH Sensor | pH of 3–8 (±0.1) | pH | Voltammetry | [103] |
Flexible Hydrogel pH sensor | pH of 5–8 (±0.2) | pH | Fluorescent Spectroscopy/Image processing | [79] |
Hydrogel pH sensor | pH of 1–8 | pH | Electrical (LC circuit) and Chemical | [104] |
Smart Bandage | Gram-Negative Bacteria, shift in wavelength by 3–4 nm | Gram-negative,-positive, E. coli, Lipid A | Electrochemical/Optical Microcavity | [105,106] |
Intelligent Hydrogel Dressing | Contrast of approximately 20,000 and 35,000 fluorescence/a.u. of S. aureus and P aeruginosa, respectively compared to HEPES | Bacteria (S. aureus, P. aeruginosa, E. coli, E. faecalis) | Electrochemical/Fluorescent Spectroscopy | [107] |
Hemin-Functionalized FET NO Sensor | 0.3 nm of NO | Nitric Oxide | Bio-electrical | [108] |
Oxygen Bandage Sensor | 0.4–0.6 mA | Oxygen | Bio-electrical | [109] |
Screen Printed Impedance Sensor | 5 × 107 CFU/mL of S. aureus | S. aureus | Electrical | [110] |
Flexible Pt thermistor | 2.7 Ω/°C | Temperature | Electrical | [111] |
Wireless thermistor | 17 Ω/°C at 35 °C | Temperature | Electrical | [112] |
Flexible Low Power Sensor | 0.2 °C temperature difference, 0.5 mmHg pressure, 3.0% RH | Moisture, Temperature, Pressure | Electrical | [113] |
Inkjet Printed Smart Bandage | ±2.3% capacitance, 8% quality factor, ±2.6% resistance | Blood, pH, Resistance | Electrical (Capacitance and Resistance) | [114] |
Flexible Sensor Array | 100–50 KΩ at 100–1 MHz | Impedance | Electrical | [115] |
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Gianino, E.; Miller, C.; Gilmore, J. Smart Wound Dressings for Diabetic Chronic Wounds. Bioengineering 2018, 5, 51. https://doi.org/10.3390/bioengineering5030051
Gianino E, Miller C, Gilmore J. Smart Wound Dressings for Diabetic Chronic Wounds. Bioengineering. 2018; 5(3):51. https://doi.org/10.3390/bioengineering5030051
Chicago/Turabian StyleGianino, Elizabeth, Craig Miller, and Jordon Gilmore. 2018. "Smart Wound Dressings for Diabetic Chronic Wounds" Bioengineering 5, no. 3: 51. https://doi.org/10.3390/bioengineering5030051