Nanotherapies make inroads in wound regeneration

DENVER – Move over, gauze, bandages, and moist wound-healing techniques. Nanomaterials are making significant inroads in wound regeneration.

Dr. Adam Friedman, director of dermatologic research at the Montefiore-Einstein College of Medicine, New York, highlighted four nanotherapies in the field of wound care.

• Antimicrobial nano-based dressings. The antibacterial properties of silver have been documented since 1000 B.C., said Dr. Friedman of the departments of dermatology and of physiology and biophysics at the medical school. Silver ions are believed to directly disrupt pathogen cell walls/membranes and suppress respiratory enzymes and electron transport components. Silver has been used commercially for decades, with demonstrated antimicrobial effects (Crede’s 1% silver nitrate eyedrops were used to prevent mother to child transmission of gonococcal eye infection); anti-inflammatory properties (silver nitrate is used in pleurodesis); and infection protection (silver nanoparticle–impregnated wound dressings prevent infection and enhance wound healing).

Silver nanoparticles have an "increased likelihood of directly interacting with the target bacteria or virus," Dr. Friedman said in an interview in advance of the annual meeting of the American Academy of Dermatology. "They bind to and/or disturb bacterial cell membrane activity as well as release silver ions much more readily then their bulk counterparts." Silver dressings currently on the market include Silvercel, Aquacel, and Acticoat.

Similarly to nanometals, the biological activity of curcumin (a water-insoluble polyphenolic compound derived from tumeric) can be used in the nanoform and has been shown to both effectively clear methicillin-resistant Staphylococcus aureus in burn wound infections and accelerate the healing of thermal burn wounds.

• Immunomodulating antimicrobial nanoparticles. One of the most promising immunomodulators in wound healing is the gaseous molecule nitric oxide (NO). This potential has yet to be realized, Dr. Friedman said, as NO is highly unstable and its site of action is often microns from its source of generation. Nanotechnology can allow for controlled and sustained release of this evasive biomolecule and make therapeutic translation a reality. "At Einstein, we are utilizing NO-generating nanoparticles to accelerate wound healing and eradicate multidrug resistant pathogens," he said. "But, because NO is integral to so many biological processes, it can do so much more. This technology is also being studied for the treatment of cardiovascular disease and even the topical treatment of erectile dysfunction."

• Gene modifying/silencing technologies. RNA interference is an endogenous mechanism to control gene expression in a variety of organisms. "We can take advantage of this process using siRNA (small interfering RNA) to manipulate limitless biological processes," Dr. Friedman explained. "While a hot area, translation to the bedside has been difficult as siRNA are very unstable and have a difficult time reaching their targets inside cells. Nanoparticles have been shown to overcome these limitations." Dr. Friedman noted how siRNA encapsulate nanoparticles targeting fidgetin-like 2 (an ATPase that cleaves microtubules), can knock down this gene in vivo, resulting in accelerated epithelial cell migration and hastened wound closure in both excisional and burn wound mouse models.

• Growth factor–releasing nanoparticles. Growth factors have been found to speed the healing of acute and chronic wounds in humans, including Regranex, a analogue of platelet-derived growth factor that is FDA-approved for treating leg and foot ulcers in diabetic patients, epidermal growth factor (donor-site wounds), fibroblast growth factor (burn wounds), and growth hormone (donor sites in burned children). "Nanomaterials offer many advantages here, from allowing for temporal release depending on the wound environment to delivering multiple factors at the same or different times, to even serving as a structural foundation for wound healing while releasing factors simultaneously," Dr. Friedman said. "The possibilities are limitless."

Dr. Friedman characterized nanomedicine as "a newborn branch of science. These promising and innovative tools should help us overcome limitations of traditional wound care, improve direct intervention on phases of wound healing, and provide better solutions for wound dressing that induce favorable wound healing environments. More work – and funding – is needed."

Dr. Friedman disclosed that he is a consultant and/or a member of the scientific advisory board for SanovaWorks, Prodigy, Oakstone Institute, Liquidia Technologies, L’Oréal, Amgen, Onset, Aveeno, GSK, MicroCures, and Nano Bio-Med. He is also a speaker for Onset and Amgen.

This article was updated March 24, 2014.

[email protected]

DENVER – Move over, gauze, bandages, and moist wound-healing techniques. Nanomaterials are making significant inroads in wound regeneration.

Dr. Adam Friedman, director of dermatologic research at the Montefiore-Einstein College of Medicine, New York, highlighted four nanotherapies in the field of wound care.

• Antimicrobial nano-based dressings. The antibacterial properties of silver have been documented since 1000 B.C., said Dr. Friedman of the departments of dermatology and of physiology and biophysics at the medical school. Silver ions are believed to directly disrupt pathogen cell walls/membranes and suppress respiratory enzymes and electron transport components. Silver has been used commercially for decades, with demonstrated antimicrobial effects (Crede’s 1% silver nitrate eyedrops were used to prevent mother to child transmission of gonococcal eye infection); anti-inflammatory properties (silver nitrate is used in pleurodesis); and infection protection (silver nanoparticle–impregnated wound dressings prevent infection and enhance wound healing).

Silver nanoparticles have an "increased likelihood of directly interacting with the target bacteria or virus," Dr. Friedman said in an interview in advance of the annual meeting of the American Academy of Dermatology. "They bind to and/or disturb bacterial cell membrane activity as well as release silver ions much more readily then their bulk counterparts." Silver dressings currently on the market include Silvercel, Aquacel, and Acticoat.

Similarly to nanometals, the biological activity of curcumin (a water-insoluble polyphenolic compound derived from tumeric) can be used in the nanoform and has been shown to both effectively clear methicillin-resistant Staphylococcus aureus in burn wound infections and accelerate the healing of thermal burn wounds.

• Immunomodulating antimicrobial nanoparticles. One of the most promising immunomodulators in wound healing is the gaseous molecule nitric oxide (NO). This potential has yet to be realized, Dr. Friedman said, as NO is highly unstable and its site of action is often microns from its source of generation. Nanotechnology can allow for controlled and sustained release of this evasive biomolecule and make therapeutic translation a reality. "At Einstein, we are utilizing NO-generating nanoparticles to accelerate wound healing and eradicate multidrug resistant pathogens," he said. "But, because NO is integral to so many biological processes, it can do so much more. This technology is also being studied for the treatment of cardiovascular disease and even the topical treatment of erectile dysfunction."

• Gene modifying/silencing technologies. RNA interference is an endogenous mechanism to control gene expression in a variety of organisms. "We can take advantage of this process using siRNA (small interfering RNA) to manipulate limitless biological processes," Dr. Friedman explained. "While a hot area, translation to the bedside has been difficult as siRNA are very unstable and have a difficult time reaching their targets inside cells. Nanoparticles have been shown to overcome these limitations." Dr. Friedman noted how siRNA encapsulate nanoparticles targeting fidgetin-like 2 (an ATPase that cleaves microtubules), can knock down this gene in vivo, resulting in accelerated epithelial cell migration and hastened wound closure in both excisional and burn wound mouse models.

• Growth factor–releasing nanoparticles. Growth factors have been found to speed the healing of acute and chronic wounds in humans, including Regranex, a analogue of platelet-derived growth factor that is FDA-approved for treating leg and foot ulcers in diabetic patients, epidermal growth factor (donor-site wounds), fibroblast growth factor (burn wounds), and growth hormone (donor sites in burned children). "Nanomaterials offer many advantages here, from allowing for temporal release depending on the wound environment to delivering multiple factors at the same or different times, to even serving as a structural foundation for wound healing while releasing factors simultaneously," Dr. Friedman said. "The possibilities are limitless."

Dr. Friedman characterized nanomedicine as "a newborn branch of science. These promising and innovative tools should help us overcome limitations of traditional wound care, improve direct intervention on phases of wound healing, and provide better solutions for wound dressing that induce favorable wound healing environments. More work – and funding – is needed."

Dr. Friedman disclosed that he is a consultant and/or a member of the scientific advisory board for SanovaWorks, Prodigy, Oakstone Institute, Liquidia Technologies, L’Oréal, Amgen, Onset, Aveeno, GSK, MicroCures, and Nano Bio-Med. He is also a speaker for Onset and Amgen.

This article was updated March 24, 2014.

[email protected]

DENVER – Move over, gauze, bandages, and moist wound-healing techniques. Nanomaterials are making significant inroads in wound regeneration.

Dr. Adam Friedman, director of dermatologic research at the Montefiore-Einstein College of Medicine, New York, highlighted four nanotherapies in the field of wound care.

• Antimicrobial nano-based dressings. The antibacterial properties of silver have been documented since 1000 B.C., said Dr. Friedman of the departments of dermatology and of physiology and biophysics at the medical school. Silver ions are believed to directly disrupt pathogen cell walls/membranes and suppress respiratory enzymes and electron transport components. Silver has been used commercially for decades, with demonstrated antimicrobial effects (Crede’s 1% silver nitrate eyedrops were used to prevent mother to child transmission of gonococcal eye infection); anti-inflammatory properties (silver nitrate is used in pleurodesis); and infection protection (silver nanoparticle–impregnated wound dressings prevent infection and enhance wound healing).

Silver nanoparticles have an "increased likelihood of directly interacting with the target bacteria or virus," Dr. Friedman said in an interview in advance of the annual meeting of the American Academy of Dermatology. "They bind to and/or disturb bacterial cell membrane activity as well as release silver ions much more readily then their bulk counterparts." Silver dressings currently on the market include Silvercel, Aquacel, and Acticoat.

Similarly to nanometals, the biological activity of curcumin (a water-insoluble polyphenolic compound derived from tumeric) can be used in the nanoform and has been shown to both effectively clear methicillin-resistant Staphylococcus aureus in burn wound infections and accelerate the healing of thermal burn wounds.

• Immunomodulating antimicrobial nanoparticles. One of the most promising immunomodulators in wound healing is the gaseous molecule nitric oxide (NO). This potential has yet to be realized, Dr. Friedman said, as NO is highly unstable and its site of action is often microns from its source of generation. Nanotechnology can allow for controlled and sustained release of this evasive biomolecule and make therapeutic translation a reality. "At Einstein, we are utilizing NO-generating nanoparticles to accelerate wound healing and eradicate multidrug resistant pathogens," he said. "But, because NO is integral to so many biological processes, it can do so much more. This technology is also being studied for the treatment of cardiovascular disease and even the topical treatment of erectile dysfunction."

• Gene modifying/silencing technologies. RNA interference is an endogenous mechanism to control gene expression in a variety of organisms. "We can take advantage of this process using siRNA (small interfering RNA) to manipulate limitless biological processes," Dr. Friedman explained. "While a hot area, translation to the bedside has been difficult as siRNA are very unstable and have a difficult time reaching their targets inside cells. Nanoparticles have been shown to overcome these limitations." Dr. Friedman noted how siRNA encapsulate nanoparticles targeting fidgetin-like 2 (an ATPase that cleaves microtubules), can knock down this gene in vivo, resulting in accelerated epithelial cell migration and hastened wound closure in both excisional and burn wound mouse models.

• Growth factor–releasing nanoparticles. Growth factors have been found to speed the healing of acute and chronic wounds in humans, including Regranex, a analogue of platelet-derived growth factor that is FDA-approved for treating leg and foot ulcers in diabetic patients, epidermal growth factor (donor-site wounds), fibroblast growth factor (burn wounds), and growth hormone (donor sites in burned children). "Nanomaterials offer many advantages here, from allowing for temporal release depending on the wound environment to delivering multiple factors at the same or different times, to even serving as a structural foundation for wound healing while releasing factors simultaneously," Dr. Friedman said. "The possibilities are limitless."

Dr. Friedman characterized nanomedicine as "a newborn branch of science. These promising and innovative tools should help us overcome limitations of traditional wound care, improve direct intervention on phases of wound healing, and provide better solutions for wound dressing that induce favorable wound healing environments. More work – and funding – is needed."

Dr. Friedman disclosed that he is a consultant and/or a member of the scientific advisory board for SanovaWorks, Prodigy, Oakstone Institute, Liquidia Technologies, L’Oréal, Amgen, Onset, Aveeno, GSK, MicroCures, and Nano Bio-Med. He is also a speaker for Onset and Amgen.

This article was updated March 24, 2014.

[email protected]