Mechanism of action

MECHANISM OF ACTION

PolyHeal® Micro

MECHANISM OF ACTION

PolyHeal® Micro

Main effects following the application of PolyHeal® Micro

PolyHeal® Micro is based on Negatively-Charged Microsphere (NCM) Technology. This technology shows an innovative mechanism of action which is unique among currently available wound-healing products.

The application of PolyHeal® triggers a synchronized series of events that switches the wound from the inflammatory phase to the proliferative phase, stimulating the patient’s own cells and leading to the reactivation of the wound-healing process1, 2

1. Cytokine modulation

One mechanism that fails in wound healing is a persistent activation of the inflammatory phase which fails to progress properly, leading to stagnation.

Cytokines participate in both the inflammatory and the proliferative phase. Controlling the local cytokine balance is essential for promoting wound healing. In this regard, the NCM promote an anti-inflammatory response by influencing selective cytokine production by adherent monocytes and macrophages.3, 4

Following a characterisation of cytokine gene expression in human monocytes treated with NCM, TNFα and IL1ß concentrations were lower in wound fluid treated with NCM than in the control group.4

2. Additional surface area for cell attachment

NCM mimic the functions of the extracellular matrix, providing an additional surface for cell attachment. The attachment of the cells involved in the healing cascade to NCM results in cell activation, proliferation and migration.5, 6

These cells are mainly endothelial cells, fibroblasts and keratinocytes.

Main results of the activation, proliferation and migration of these cells are:

  • Endothelial cells: Their main function is to favor angiogenesis (the formation of new blood vessels in the wound). The treatment of chronic wounds with NCM has shown positive results in the formation of new blood vessels.7
  • Fibroblasts: Their main function is collagen synthesis. An increase in collagen has been observed, both in vivo and in vitro.7
  • Keratinocytes: their main function is wound epithelialization. Treatment with NCM increases the mass of keratinocytes (human, in vitro).4

3. Metalloproteinases sequestration

PolyHeal® Micro decreases the concentration of metalloproteinases (MMP) in the wound bed. MMP are enzymes involved in the remodelling of the connective tissue during wound healing. An increased concentration of MMP destroys the components of the extracellular matrix, impairing tissue regeneration.

When the metalloproteinases come into contact with the NCM they can be adsorbed onto their surface. This neutralizes their action because of a decrease in their concentration, reducing the degradation of the extracellular matrix and favouring tissue regeneration.2, 9

The application of PolyHeal® triggers a synchronized series of events that switches the wound from the inflammatory phase to the proliferative phase, stimulating the patient’s own cells and leading to the reactivation of the wound-healing process1, 2

1. Cytokine modulation

One mechanism that fails in wound healing is a persistent activation of the inflammatory phase which fails to progress properly, leading to stagnation.

Cytokines participate in both the inflammatory and the proliferative phase. Controlling the local cytokine balance is essential for promoting wound healing. In this regard, the NCM promote an anti-inflammatory response by influencing selective cytokine production by adherent monocytes and macrophages.3, 4

Following a characterisation of cytokine gene expression in human monocytes treated with NCM, TNFα and IL1ß concentrations were lower in wound fluid treated with NCM than in the control group.4

2. Additional surface area for cell attachment

NCM mimic the functions of the extracellular matrix, providing an additional surface for cell attachment. The attachment of the cells involved in the healing cascade to NCM results in cell activation, proliferation and migration.5, 6

These cells are mainly endothelial cells, fibroblasts and keratinocytes.

Main results of the activation, proliferation and migration of these cells are:

  • Endothelial cells: Their main function is to favor angiogenesis (the formation of new blood vessels in the wound). The treatment of chronic wounds with NCM has shown positive results in the formation of new blood vessels.7
  • Fibroblasts: Their main function is collagen synthesis. An increase in collagen has been observed, both in vivo and in vitro.7
  • Keratinocytes: their main function is wound epithelialization. Treatment with NCM increases the mass of keratinocytes (human, in vitro).4

3. Metalloproteinases sequestration

PolyHeal® Micro decreases the concentration of metalloproteinases (MMP) in the wound bed. MMP are enzymes involved in the remodelling of the connective tissue during wound healing. An increased concentration of MMP destroys the components of the extracellular matrix, impairing tissue regeneration.

When the metalloproteinases come into contact with the NCM they can be adsorbed onto their surface. This neutralizes their action because of a decrease in their concentration, reducing the degradation of the extracellular matrix and favouring tissue regeneration.2, 9

PolyHeal® Micro reactivates the healing process and accelerates the production of
granulation tissue, favouring wound closure.1

BEFORE

THE APPLICATION OF POLYHEAL® MICRO

AFTER

THE APPLICATION OF POLYHEAL® MICRO
Chronic wound without
extracellular matrix

In a chronic wound situation there is an overall decrease in
all components of the extracellular matrix, cells lose their ability
to proliferate and, as a consequence, end up in apoptosis.

Re-establishment of
the extracellular matrix

The NCM provide an additional surface for cell attachment and activation.
This increases the number of cells in the wound bed, re-establishing
the extracellular matrix and therefore reactivating the healing process.

BEFORE

THE APPLICATION OF POLYHEAL® MICRO
Chronic wound without
extracellular matrix

In a chronic wound situation there is an overall decrease in all components of the extracellular matrix, cells lose their ability to proliferate and, as a consequence, end up in apoptosis.

AFTER

THE APPLICATION OF POLYHEAL® MICRO
Re-establishment of
the extracellular matrix

The NCM provide an additional surface for cell attachment and activation. This increases the number of cells in the wound bed, re-establishing the extracellular matrix and therefore reactivating the healing process.

Continue reading to learn more about how PolyHeal® Micro reactivates cells in the wound bed.

The NCM mimic the functions of the extracellular matrix

Negatively-charged Microspheres provide an additional surface to which a variety of cells and macromolecules involved in the healing process can attach and interact. This promotes the reactivation of the stagnant healing process.5, 6

Cell attachment

Cell attachment to NCM in the wound bed results in morphological and functional cell changes that reactivate healing.7, 8

Electron microscopy image of a myofibroblast attached to a NCM

Biomolecular recreation of cell attachment

References

  1. Shoham Y, et al. Wound ‘dechronification’ with negatively-charged polystyrene microspheres: a double-blind RCT. J Wound Care. 2013 Mar; 22(3):144-55.
  2. Govrin J, et al. New method for treating hard-to-heal wounds: clinical experience with charged polystyrene microspheres. Wounds UK. 2010; 6(4); 52-61.
  3. Brodbeck W, et al. Biomaterial surface chemistry dictates adherent monocyte/macrophage cytokine expression in vitro. Cytokine vol.18, issue 6, June 2002, page. 311-319.
  4. Correa L, Mediavilla E, Ritter V. NCM reestablishes local cytokine milieu to promote an anti-inflammatory type of response. Poster ID 490. Presented in GNEAUPP 2018. Valencia Nov 28th-30th 2018.
  5. Saltzman W.M, et al. Cell interaction with polymers. Principles of tissue engineering (3rd edition), 2007, page. 279-296.
  6. Carré A, et al. How Substrate Properties Control Cell Adhesion. A Physical–Chemical Approach. Journal of Adhesion Science and Technology. 2010; 24:5, 815-830.
  7. Kaufman H, et al. Reawakening the most hard-to-heal chronic wounds: long term outcomes of a RCT with active negatively charged microsphere (NCM) technology. Proceedings of a satellite symposium. The 27th European Wound Management Association Conference. May 4th, 2017, Amsterdam.
  8. Correa L, Peter R, Clerici G, Ritter V. Negatively charged microspheres provide an additional surface for cell attachment leading to proliferation, tissue regeneration and wound healing. EP 216. Presented in EWMA 2017. Amsterdam May 3rd-5th 2017.
  9. Renò F, et al. Adsorption of matrix metalloproteinases onto biomedical polymers: a new aspect in biological acceptance. J Biomater Sci Polym Ed. 2008;19(1):19-29.