U.S. patent application number 16/321355 was filed with the patent office on 2019-06-13 for blue light photobiomodulation.
This patent application is currently assigned to Urgo Recherche Innovation et Developpement. The applicant listed for this patent is Blue Light Photobiomodulation GDBR, Urgo Recherche Innovation et Developpement. Invention is credited to Fabiola Arpino, Anja Becker, Marielle Bouschbacher, Norbert Gretz, Anna Klapczynski, Natalia Kuch, Julien Steinbrunn.
Application Number | 20190175936 16/321355 |
Document ID | / |
Family ID | 56557551 |
Filed Date | 2019-06-13 |
United States Patent
Application |
20190175936 |
Kind Code |
A1 |
Gretz; Norbert ; et
al. |
June 13, 2019 |
Blue Light Photobiomodulation
Abstract
The invention is directed to a light source device (10)
comprising a light emitting element (12) for emitting a blue light
having a wavelength ranging from 435 to 500 nm, the light source
device (10) being configured to provide the blue light to at least
one cell (C) at a transmitted fluence ranging from 0.01 to 18.
J/cm.sup.2 to promote or induce growth and proliferation of the
cell (C) and wherein the light emitting element (12) has a power
density ranging from 0.05 to 30 mW/cm.sup.2. The invention is also
directed to a light source assembly comprising a product adapted to
be in contact with the skin or a wound and a light source device
(10) connected to the product for providing blue light to at least
one skin cell (C), preferably of the wound.
Inventors: |
Gretz; Norbert; (Mannheim,
DE) ; Arpino; Fabiola; (Mannheim, DE) ;
Becker; Anja; (Mannheim, DE) ; Klapczynski; Anna;
(Mannheim, DE) ; Kuch; Natalia; (Mannheim, DE)
; Bouschbacher; Marielle; (Chambolle-Musigny, FR)
; Steinbrunn; Julien; (Messigny et Vantoux, FR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Urgo Recherche Innovation et Developpement
Blue Light Photobiomodulation GDBR |
Chenove
Mannheim |
|
FR
DE |
|
|
Assignee: |
Urgo Recherche Innovation et
Developpement
Chenove
FR
Blue Light Photobiomodulation GDBR
Mannheim
DE
|
Family ID: |
56557551 |
Appl. No.: |
16/321355 |
Filed: |
July 27, 2017 |
PCT Filed: |
July 27, 2017 |
PCT NO: |
PCT/EP2017/068951 |
371 Date: |
January 28, 2019 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 5/0616 20130101;
A61N 2005/0663 20130101; A61N 2005/0651 20130101; A61N 5/0624
20130101 |
International
Class: |
A61N 5/06 20060101
A61N005/06 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 28, 2016 |
EP |
16181721.8 |
Claims
1. A light source device comprising a light emitting element for
emitting a blue light having a wavelength ranging from 435 to 500
nm, the light source device being configured to provide the blue
light to at least one cell at a transmitted fluence ranging from
0.01 to 18.5 J/cm.sup.2 to promote or induce growth and
proliferation of the cell and wherein the light emitting element
has a power density ranging from 0.05 to 30 mW/cm.sup.2.
2. The light source device of claim 1, wherein the cell is selected
from a skin cell.
3. The light source device according to claim 2, wherein the skin
cells are keratinocytes or fibroblasts.
4. The light source device of claim 1, wherein the dominant
emission wavelength ranges from 450 to 490 nm.
5. The light source device according to claim 1, wherein the light
source device is configured to provide the blue light at a
transmitted fluence so that the cell receives an effective fluence
ranging from 0.01 to 10 J/cm.sup.2.
6. The light source device according to claim 1, wherein the light
emitting element has a power density ranging from 20 to 25
mW/cm.sup.2.
7. The light source device according to claim 1, wherein said light
emitting element comprises at least one LED.
8. The light source device according to claim 1, further comprising
a power source providing electrical power to said light emitting
element.
9. The light source device according to claim 8, wherein said power
source is a battery.
10. The light source device according to claim 1 further comprising
at least one among a microchip processor, a control unit, a
communication unit, an external port and a sensor.
11. A light source assembly comprising: a product adapted to be in
contact with the skin or a wound; a light source device according
to claim 1 connected to the product for providing blue light to at
least one skin cell, preferably of the wound.
12. The light source assembly according to claim 11, wherein the
product is one among a dressing, a strip, a compression means, a
band-aid, a patch, a gel, a film-forming composition and a rigid or
flexible support.
13. The light source assembly according to claim 11, wherein the
dressing comprises at least a hydrocolloid or an adhesive layer in
contact with the skin or the wound.
14. The light source assembly according to claim 11, wherein the
light source assembly is adapted to dispose the light emitting
element in a position wherein the light emitting element is facing
the skin.
Description
TECHNICAL FIELD
[0001] This invention relates to a light source device able to
promote or induce growth and proliferation of skin cells, notably
for the treatment of wounds and injuries, through a
photobiomodulation mean. The invention also relates to a light
source assembly comprising such a light source device.
BACKGROUND OF THE INVENTION
[0002] Healing of a wound is a natural physiopathological process,
the human and animal tissues being able to repair lesions by
specific processes of reparation and regeneration.
[0003] Natural healing of a wound proceeds mainly according to
three major chronological sequences. Each one of these sequences is
characterized by specific cellular activities and is controlled by
a multiplicity of signals of regulation (as well as positive and
negative) which, collectively, orchestrate and frame the
progression of the process of repair. One distinguishes as follows:
[0004] the inflammatory phase; [0005] the phase of proliferation
(which includes the phase of granulation and epithelialization; and
[0006] the phase of remodeling.
[0007] The first phase, also called the inflammatory phase, begins
since the rupture from the blood-vessels, event which starts the
formation of a clot (coagulation of blood) mainly made up of fibrin
and fibronectin, and which will constitute a provisional matrix.
This matrix fills the lesion partly and will allow the migration,
within the injured zone, of inflammatory cells recruited to ensure
the debridement of the wound. This phase is characterized by the
infiltration on the site of the lesion, of many inflammatory cells
(polynuclear, macrophages) ensuring the defense of the organization
against possible foreign micro-organisms as well as the cleaning of
the wound or debridement.
[0008] The second phase corresponds to the development of the
granulation tissue. One observes initially a colonization of the
wound by migration and proliferation of the fibroblasts. Then, the
migration of endothelial cells starting from the healthy vessels
will allow the neovascularization, or angiogenesis, of the injured
tissue. In the granulation tissue, the fibroblasts are activated
and will be differentiate into myofibroblasts that present
important contractile properties. These properties are generated by
the actin microfilaments that thus allow a contraction of the
wound. These myofibroblasts play a main function in the formation
and the contraction of granulation tissue which will lead to the
healing of the lesion. There is then migration of the keratinocytes
starting from the edges of the wound, leading to the rebuilding of
the skin.
[0009] This phase of development of the granulation tissue is
initiated following a preliminary reduction in the general
inflammatory state of the lesion, with the progressive
disappearance of polynuclear and the appearance of macrophages.
[0010] Nevertheless, certain types of wounds do not heal correctly,
the 3 key stages of the process described previously turned in an
abnormal way. Indeed the speed and the quality of the healing of a
wound depend on intrinsic and extrinsic factors. This process of
repair can thus be abnormally prolonged according to: [0011]
etiology of the wound; [0012] its state and its localization;
[0013] occurrence of an infection caused by the presence of certain
infectious agent like Staphylococcus aureus or Pseudomonas
aeruginosa; the existence of a preexistent pathology (like the
diabetes, an immunizing deficiency, a venous insufficiency, etc);
[0014] external environment; or genetic factors predisposing or not
with disorders of the wound healing.
[0015] To enhance the process of wound healing, for both wounds
which heal naturally and chronic wounds, it is known from the art
to use phototherapy. Two types of phototherapies are known, the
photodynamic therapy and the photobiomodulation.
[0016] Photodynamic therapy is a method that uses a
photosensitizer, or photosensitizing agent, which is disposed or
injected near skin or wound cells and activated by a light of a
specific wavelength. Photosensitizers have the ability to interact
with the nearby skin cells when exposed to a light with a specific
wavelength. Photodynamic therapy is thus an indirect phototherapy
because the light is provided to the photosensitizer to treat the
skin cells, not directly to the skin cells.
[0017] Photobiomodulation is a method allowing to have a biological
effect on skin or wound cells directly, which means without the
need of any provisional product or composition to transpose or
potentialize any biological effect engendered by the light source.
This method can be distinguished from the photodynamic therapy
which needs absolutely and every time the intervention of an
intermediate product (photosensitizer or a photosensitizing agent)
between the light source and the cells to potentialize the
biological effect of the light on cells. In other words, in
photobiomodulation, light has a direct effect on cells whereas, in
photodynamic therapy, light has an indirect effect on cells via the
activated photosensitizer. As mentioned in the technical field
above, the present invention is directed to photobiomodulation.
[0018] Furthermore, in phototherapy, it is well known to determine
the wavelength of the light to be provided depending on the type of
effect that is expected on the skin cells. Particularly, light
having a wavelength between 435 and 500 nm (blue light) has
antibacterial effects and also act on human cells. [Ashkenazi H.,
Malik Z., Harth Y., Nitzan Y., Eradication of Propionibacterium
acnes by its endogenic porphyrins after illumination with high
intensity blue light. FEMS Immunology and Medical Microbiology
2003, 35:17-24].
[0019] More particularly, it was shown that blue light irradiation
enables to inhibit the proliferation and migration of skin cells
[Taflinski, L, Demir, E, Kauczok, J, Fuchs, P C, Born, M, Suschek,
C V, Oplander, C: Blue light inhibits transforming growth
factor-beta1-induced myofibroblast differentiation of human dermal
fibroblasts. Experimental dermatology 2014, 23: 240-246] and
[Mamalis A., Garcha M., Jagdeo J. Light Emitting Diode-Generated
Blue Light Modulates Fibrosis Characteristics: Fibroblast
Proliferation, Migration Speed, and Reactive Oxygen Species
Generation Lasers in Surgery and Medicine 201547: 210-215]. It is
also well known that inhibiting the proliferation of skin cells can
be useful to enhance the phase of remodeling during wound
healing.
[0020] As an example of the effect of blue light, document
US-A-2014/0277293 is directed to the use of LED generated low-level
light therapy. Tests show that light emitting diode having a
dominant emission wavelength of 415 nm, wavelength comprised
between 385 and 445 nm, and providing an effective fluence
comprised between 0 and 35 J/cm.sup.2 during many defined
irradiation times which means that the irradiance of the light
source used is of 43 mW/cm.sup.2, allows to inhibit fibroblast
proliferation. This document thus supports the fact that blue light
emission is generally known as an inhibitor of the proliferation of
specific types of skin cells.
[0021] It should be noted that toxicity occurs for shorter and
dominant emission wavelengths of blue light between 410 and 420 nm
[Oplander, C, Hidding, S, Werners, F B, Born, M, Pallua, N,
Suschek, C V: Effects of blue light irradiation on human dermal
fibroblasts. Journal of photochemistry and photobiology B, Biology
2011, 103: 118-125]. Therefore, the blue light emission with a
dominant emission wavelength of 415 nm disclosed in the method of
US-A-2014/0277293 might be toxic.
SUMMARY OF THE INVENTION
[0022] It was surprisingly discovered that irradiating cells with
blue light under specific conditions can have an unexpected
technical effect consisting in promoting or inducing growth and
proliferation of irradiated cells. Indeed, this is particularly
unexpected because blue light is generally known for
anti-proliferation effect whereas these experimentations showed
that blue irradiation under specific conditions enables to have
proliferation effect, preferably at specific dominant emission
wavelength, irradiance and/or fluence.
[0023] Proliferation effect is particularly advantageous to enhance
the phase of proliferation during wound healing. Indeed, inducing a
proliferation effect during the phase of proliferation and
granulation is the key to enhance the wound healing process.
[0024] Furthermore, irradiating cells of a wound with blue light
enables to benefit from all the known effects of blue light, such
as antibacterial and anti-inflammatory effects, in addition to the
unexpected proliferation effect.
[0025] The unexpected technical effect is achieved with a light
source device comprising a light emitting element for emitting a
blue light having a wavelength ranging from 435 to 500 nm, the
light source device being configured to provide the blue light to
at least one cell (C) at a transmitted fluence ranging from 0.01 to
18.5 J/cm.sup.2 to promote or induce growth and proliferation of
the cell (C) and wherein the light emitting element (12) has a
power density ranging from 0.05 to 30 mW/cm.sup.2.
[0026] According to an embodiment of the light source device, the
cell is selected from a skin cell.
[0027] According to another embodiment, skin cells are
keratinocytes or fibroblasts.
[0028] According to another embodiment, the dominant emission
wavelength ranges from 450 to 490 nm, more particularly from 450 to
460 nm.
[0029] According to another embodiment, the light source device is
configured to provide the blue light at a transmitted fluence so
that the cell receives an effective fluence ranging from 0.01 to 10
J/cm.sup.2.
[0030] According to another embodiment, the light emitting element
has a power density ranging from 20 to 25 mW/cm.sup.2, and
preferably of 23 mW/cm.sup.2.
[0031] According to another embodiment, said light emitting element
comprises at least one LED.
[0032] According to another embodiment, the light source device
comprises a power source providing electrical power to said light
emitting element.
[0033] According to another embodiment, said power source is a
battery.
[0034] According to another embodiment, the light source device
comprises at least one among a microchip processor, a control unit,
a communication unit, an external port and a sensor.
[0035] It is another object of the invention to provide a light
source assembly comprising a product adapted to be in contact with
the skin or a wound and a light source device as described above
connected to the product for providing blue light to at least one
skin cell, preferably of the wound.
[0036] According to an embodiment of the light source assembly, the
product is one among a dressing, a strip, a compression means, a
band-aid, a patch, a gel, a film-forming composition and a rigid or
flexible support, preferably a dressing.
[0037] According to another embodiment, the dressing comprises at
least a hydrocolloid or an adhesive layer in contact with the skin
or the wound.
[0038] According to another embodiment, the light source assembly
is adapted to dispose the light emitting element in a position
wherein the light emitting element is facing the skin, preferably
facing a wound formed on the skin.
BRIEF DESCRIPTION OF THE DRAWINGS
[0039] FIG. 1 represents in a cross section view an embodiment of a
photobiomodulation device used in the treatment of various skin
conditions or for promoting or inducing growth and proliferation of
cells in vitro or in vivo.
[0040] FIG. 2 is a schematic representation showing the
keratinocyte proliferation, 24 hours after different energy
densities with blue light irradiation (transmitted fluence in
J/cm.sup.2).
[0041] FIG. 3 is a zoom of FIG. 2 in the transmitted fluence range
of 0.01 to 30 J/cm.sup.2.
[0042] FIG. 4 is a schematic representation showing the fibroblast
proliferation, 24 hours after different energy densities with blue
light irradiation (transmitted fluence in J/cm.sup.2).
DETAILED DESCRIPTION
[0043] The present invention will be described below relative to
several specific embodiments. Those skilled in the art will
appreciate that the present invention may be implemented in a
number of different applications and embodiments and is not
specifically limited in its application to the particular
embodiment depicted herein.
[0044] For the purpose of the present invention, the following
terms are defined.
[0045] The term "Wavelength" is the distance between two peaks of a
wave. The symbol for wavelength is .lamda. (lambda) and the unit of
measurement is nanometers (nm).
[0046] The term "Dominant emission wavelength" is the wavelength or
a narrow range of wavelengths the light source emits the majority
of the time. The term "power" refers to the rate at which work is
perform; the unit of power is Watt (W) and since the light output
power is low it is expressed in milliwatts (mW).
[0047] The term "power density" or "light intensity", or
"irradiance", or "exitance" is the power divided by the area of the
target being illuminated by the light and is expressed in
mW/cm.sup.2.
[0048] The term "fluence" or "energy density" or "dose" expressed
in Joules per cm.sup.2 (J/cm.sup.2) is the product of power (mW)
and time per spot size (cm.sup.2).
[0049] The term "photobiomodulation" is the ability of the light
source device to have a biological effect on cells, in particular
on skin cells, directly, which means without the need of any
provisional product or composition to transpose or potentialize any
biological effect engendered by the light source. This term can be
distinguished from the term of "photodynamic therapy" which needs
absolutely and every time the intervention of an intermediate
product between the light source and the cells to potentialize the
biological effect of the light on cells.
[0050] A first object of the invention is a light source device
comprising a light emitting element for emitting a blue light
having a wavelength ranging from 435 to 500 nm, the light source
device being configured to provide the blue light to at least one
cell (C) at a transmitted fluence ranging from 0.01 to 18.5
J/cm.sup.2 to promote or induce growth and proliferation of the
cell (C) and wherein the light emitting element (12) has a power
density ranging from 0.05 to 30 mW/cm.sup.2.
[0051] According to FIG. 1, a light source device 10 comprising a
light emitting element 12 for emitting a blue light having a
wavelength ranging from 435 to 500 nm is proposed. The light source
device 10 is able to emit light at wavelengths within the range of
435 to 500 nm, preferably within a specific dominant emission
wavelength of 450-490 nm and preferably within a specific dominant
emission wavelength of 450-460 nm. More particularly, the chosen
dominant emission wavelength may be 453 nm. It should be noted that
emitting light at wavelengths within the range of 435 to 500 nm
allows blue light emission not to be toxic, contrary to the chosen
blue light wavelength range of US-A-2014/0277293, because of most
of the emitted wavelengths are comprised in another dominant
emission wavelength.
[0052] Furthermore, the light source device 10 is configured to
provide blue light to cells C at an irradiance and a fluence (dose
or energy density) able to promote or induce growth and
proliferation of cells C. The fluence at which blue light is
provided to the cells C corresponds to the specific conditions,
particularly specific condition of irradiance and exposition with a
light source having a specific dominant emission wavelength;
allowing to obtain the unexpected technical effect with regard to
the prior art, such as US-A-2014/0277293. Indeed, it was observed
that monitoring the irradiance of the provided blue light allows to
have proliferation effect so that growth and proliferation of
irradiated cells are promoted or induced. Particularly, it was
observed that blue light irradiation have a proliferation effect on
keratinocytes and fibroblasts.
[0053] It seems that the key notions of dominant emission
wavelength and/or irradiance give a particular benefit to the
unexpected proliferative effect on keratinocytes and fibroblasts
from skin wound.
[0054] Experimentation showed that proliferation effect may be
obtained thanks to the action of blue light irradiation on cell
pathways. Indeed, it was observed that providing the cells C with
blue light induces a downregulation or an upregulation of different
pathways. Particularly, the TGF-BETA signaling pathway (KEGGID:
4350) is downregulated. This pathway leads to the differentiation
of fibroblasts. Therefore, reducing fibroblast's differentiation
explain the activation of the proliferation (because the 2
functions are opposite in cells behavior). On the contrary, ErbB
signaling pathway is activated, explaining the increase of the
fibroblast, as EGF has been linked to their proliferation. [Yu et
al. Effect of EGF and bFGF on fibroblast proliferation and
angiogenic cytokine production from cultured dermal substitutes. J
Biomater Sci Polym Ed. 2012; 23(10):1315-24].
[0055] The growth and proliferation of cells, preferably skin
cells, may be performed in vitro or in vivo. Indeed, cells may be
in culture or may be cells of a tissue, preferably a mammal
tissue.
[0056] The light source device 10 may be configured to provide
light at a specific fluence to a mammal skin tissue or to in vitro
cells to provide the proliferation effect. Thus, the light source
device 10 is particularly useful in wound healing. According to
this embodiment, the light source device transmits the blue light
onto the surface of a wound.
[0057] Depending on many interference means, as described above,
disposed between the cells and the light source, the effective
fluence of the blue light received by the skin cells may be lower
than the fluence transmitted by the light emitting element. Indeed,
it was also observed that a larger fluence has to be generally
transmitted by the light emitting element 12 to provide a
predetermined fluence of blue light to skin cells C, i.e. an
effective fluence of blue light adsorbed by cells. Indeed, during
the emission, a part of the blue light is adsorbed by other
elements than skin cells C which induces a loss of blue light.
Therefore, the light source device 10 is configured to provide blue
light at a transmitted fluence so that the skin cells C receive a
predetermined fluence or an effective fluence. Depending on the
elements that can be present between the light emitting element and
the target cells, the attenuation or absorption effect of the light
may lead to an attenuation ranging from 20% to 60% or from 30% to
50% of the energy density, particularly around 45%.
[0058] To obtain the unexpected proliferation effect with skin
cells, preferably with keratinocytes, the irradiance or power
density is in the range of about 0.05 mW/cm.sup.2 to about 30
mW/cm.sup.2, particularly 0.1 mW/cm.sup.2 to 1 mW/cm.sup.2, 1
mW/cm.sup.2 to about 2 mW/cm.sup.2, 2 mW/cm.sup.2 to 5 mW/cm.sup.2,
5 mW/cm.sup.2 to 10 mW/cm.sup.2, 15 mW/cm.sup.2 to 25 mW/cm.sup.2
or any irradiance in a range bounded by, or between, any of these
values. The power density used to treat target cells or target
tissue is of 0.05 to 30 mW/cm.sup.2, preferably of 15 to 25
mW/cm.sup.2, preferably of 20 to 25 mW/cm.sup.2 and more
particularly of 23 mW/cm.sup.2.
[0059] The effective dose or fluence received by skin cells, in
particular of a wound or a given surface of skin tissue, may be
about 0.01 J/cm.sup.2 to about 0.1 J/cm.sup.2, or about 0.1
J/cm.sup.2 to about 10 J/cm.sup.2, or about 1 J/cm.sup.2 to about 2
J/cm.sup.2, or about 2 J/cm.sup.2 to about 3 J/cm.sup.2, about 3
J/cm.sup.2 to about 4 J/cm.sup.2, or about 4 J/cm.sup.2 to about 5
J/cm.sup.2, or about 5 J/cm.sup.2 to about 6 J/cm.sup.2, or about 6
J/cm.sup.2 to about 7 J/cm.sup.2, or about 7 J/cm.sup.2 to about 8
J/cm.sup.2, or about 8 J/cm.sup.2 to about 9 J/cm.sup.2, or about 9
J/cm.sup.2 to about 10 J/cm.sup.2, or any light dose in a range
bounded by, or between, any of these values. Preferably, the
effective fluence used to treat target cells or target skin tissue
is of about 0.01 J/cm.sup.2 to about 10 J/cm.sup.2.
[0060] As indicated above, the fluence (dose or energy density)
notably depends on both irradiance (mW/cm.sup.2) and time.
Therefore, obtaining the predetermined fluence may be accomplished
by using a higher power light source, which may provide the needed
energy in a shorter period of time, or a lower power light source
may be used for a longer period of time. Thus, a longer exposure to
the light may allow a lower power light source to be used, while a
higher power light source may allow the treatment to be done in a
shorter time.
[0061] The duration of radiation or light exposure administered to
a skin tissue or a culture of skin cells, such as keratinocytes,
may also vary. In some embodiments, the exposure ranges from at
least 1 second, at least few seconds, or at least 1 minute, or at
least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,
19, 20 minutes; or up to about 1 hour or, for any amount of time in
a range bounded by, or between, any of these values.
[0062] According to a specific embodiment, the light source device
is used in the growth and proliferation of dermis cells, in
particular of fibroblasts under specific conditions. Particularly,
it was observed that proliferation effect occurs on fibroblasts
when provided with an effective fluence of about 6 J/cm.sup.2 with
a power density of about 23 mW/cm.sup.2 during about 7.5 minutes.
Similarly, it was observed that proliferation effect occurs on
keratinocytes when provided with an effective fluence of about 1 to
10 J/cm.sup.2 with a power density of about 23 mW/cm.sup.2 during
about 7.5 minutes
[0063] For thermal issues, light source device may be configured to
irradiate cells either continuously or in pulses. Indeed, pulsed
light irradiation will typically be preferred than continuous light
if there are some thermal issues; indeed, light source provides
heating. The decision whether to use constant irradiation of pulsed
light irradiation depends on the exact application and on the total
desired irradiation. When the light exposure depends on the
duration of a pulsed light, the net light time may be determined by
the sum of the duration of each pulse.
[0064] The light emitting element 12 is a device able to perform
photobiomodulation. An example of such a light emitting element 12
is a light-emitting diode (LED or OLED, preferably LED) or a lamp
which is able to emit light at wavelengths within the ranges of 435
to 500 nm and having preferably a dominant emission wavelength
comprised between 450-460 nm, as well as at a dominant emission
wavelength of 453 nm. In the embodiment shown on FIG. 1, the light
emitting element 12 comprises three light-emitting diodes.
Alternatively, the light emitting element 12 may comprise one or
more light-emitting diode (or lamp) able to emit a blue light
having a wavelength ranging from 435 to 500 nm, having preferably a
dominant emission wavelength comprised between 450 to 460 nm or
having a dominant emission wavelength of about 453 nm.
[0065] For supplying electricity to the light emitting element 12,
the light source device 10 may comprise a power source connected to
the light emitting element 12. The power source may comprise an
electric cable to connect to a power grid. Alternatively, the power
source may be a battery. The light source device 10 is compact and
able to communicate with a smartphone or a tablet thanks to a
wireless communication protocol (Bluetooth or Bluetooth smart or
Bluetooth Low Energy, preferably Bluetooth Low Energy).
[0066] For controlling the light emitting element 12, the light
source device 10 may comprise at least one among a LED Driver, a
sensor, a microchip processor, a control unit, a communication unit
and an external port, an antenna, a memory.
[0067] A sensor may allow the light source device 10 to measure
parameters of the wound healing. These parameters may be for
example the temperature and the oxygenation level of the wound.
[0068] The microchip processor or the control unit may allow the
light source device 10 to monitor the supply of electricity to the
light emitting element 12 to guarantee an optimum or desired blue
light exposure. For example, the microchip processor or the control
unit may control whether the light exposure is continuous or in
pulses as well as the frequency and the duration of the pulses
depending on predetermined parameters or live parameters such as
values measured by a sensor of the light source device 10.
[0069] Furthermore, a communication unit may allow a user to
recover data from or transmit data to the light source device 10.
For example, data may be transmitted to a smartphone or any other
external device, notably an external device comprising a screen to
display information useful to the user. The communication unit may
be configured for wireless transmission or wired communication. In
the case of a wired communication, the light source device 10 may
comprise an external port connected to the communication unit for
data transmission. Alternatively, the communication unit may be
configured for both wireless and wired communication.
[0070] Moreover, the light source device 10 may be included in a
light source assembly (not shown) which comprises a product adapted
to be in contact with the skin or a wound formed on the skin. In
this case, the light source device 10 is connected to the product
for providing blue light to at least one skin cell of the skin or
the wound.
[0071] For improving blue light effect, the light source assembly
may be adapted to dispose the light emitting element 12 in a
position wherein the light emitting element 12 is facing the skin,
preferably facing a wound formed on the skin. In other words, the
light source assembly is also adapted to place the light emitting
element on the facing page of the skin, preferably of the
wound.
[0072] Furthermore, the light source device 10 may be configured so
that blue light is irradiated to the skin cells or the wound
through the product. In doing so, the light source device 10 can
irradiate the skin cells or the wound without direct contact.
[0073] The light source assembly may be configured to allow setting
or predetermining of the distance between the light emitting
element 12 and the skin. Indeed, light intensity decreases with the
square of the distance from the source of the light. For example,
light 1 meter away from a source is four times as intense as light
2 meters from the same source. Therefore, setting the distance
between the light emitting element 12 and the skin allows to
monitor the irradiance and thus the fluence provided to the skin
cells. The distance between the light emitting element 12 and the
skin may be predetermined from 0 to 50 mm, and preferably 0 to 20
mm in the case of a wound dressing for example. The distance
between the light emitting element 12 and the skin may be of
several centimeters in the case of a lamp used alone for
example.
[0074] For setting or predetermining the distance between the light
emitting element 12 and the skin, the dimension of the product may
be chosen to predetermine or set the distance between the light
emitting element 12 and the skin cells. Alternatively or in
combination, the light source assembly may further comprise an
adjustable element for adjusting the distance between the light
emitting element 12 and the skin.
[0075] The light source device 10 may also be configured so that
the light emitting element 12 may be selectively orientated to
better target the skin cells to be irradiated. This orientation, or
homogenization of the light emitting element 12 allows the
irradiation to be more adapted to the geometry and the
characteristics of a wound. These advantages become even more
significant when the light source device 10 comprises a plurality
of light emitting elements 12. In this case, the light emitting
elements 12 may be orientated independently from each other to
widen the irradiated area.
[0076] Furthermore, the light source device 10 may comprise a lens
for focusing the light onto the target cells or tissue to make the
irradiation more precise.
[0077] The product may be one among a dressing, a strip, a
compression means, a band-aid, a patch, a gel and a rigid or
flexible support, a film-forming composition or similar.
Furthermore, in an embodiment of the light source assembly, the
product may be arranged so that the light emitting element 12 is
disposed on the interior of the product or in its inferior or
superior surface. In this embodiment, the product adapted to
contact the skin or a wound is preferably a dressing. The dressing
may comprise at least a hydrocolloid or an adhesive layer in
contact with the skin or the wound.
[0078] The light source assembly may be of any size or shape. In
one particular embodiment, the assembly may be 8.times.8 cm in
size. In another embodiment, the assembly may be 4.times.4 cm in
size. The product may comprise an interior layer comprising a mesh
material and a tissue gel. The mesh material allows exudate from a
wound to which the dressing is applied to be absorbed into the
dressing whilst allowing the tissue gel to flow through it so that
it can be absorbed by a wound being treated.
[0079] For allowing the light source assembly to be reusable while
avoiding repetitive cleanup, the product may be disposable and
interchangeable. In other words, the product may be configured to
be separated from the light source device 10 so that a same light
source device 10 can be used several times without the need of a
cleanup. It also allows to change the electronic elements included
in the light source device 10 for maintenance, for example for
recharging the battery.
[0080] Moreover, the effect of irradiation may at times be enhanced
by the addition of photosensitizer substances to the target cells
or tissue. The concentration of such substance is substantially
lower than concentrations used in photodynamic therapy. For
example, a culture of skin cells, such as fibroblasts or
keratinocytes, may be supplemented with small amounts of a
photosensitizer substance, such as hematoporphyrin derivatives
prior to light irradiation. Such substances may also be applied
topically onto the skin prior to the light therapy.
[0081] A method for inducing or promoting growth and proliferation
of cells is also proposed. The method may be performed by any light
source device but preferably by the light source device 10 and the
light source assembly described above.
[0082] Cells or tissue are irradiated with a light at wavelengths
between 435 to 500 nm, and preferably having a dominant emission
wavelength comprised between 450 and 460 nm. More particularly, the
chosen dominant emission wavelength may be of 453 nm. The method
may be performed in vivo or in vitro. Cells or tissue may be in
culture or directly from a mammal tissue.
[0083] For inducing or promoting growth and proliferation of cells,
cells or tissue may be irradiated to receive an effective fluence
comprised between 0.01 and 10 J/cm.sup.2.
[0084] For inducing or promoting growth and proliferation of cells
also, light emitting source used in this method is in the range of
about 0.05 mW/cm.sup.2 to about 30 mW/cm.sup.2, particularly 0.1
mW/cm.sup.2 to 1 mW/cm.sup.2, 1 mW/cm.sup.2 to about 2 mW/cm.sup.2,
2 mW/cm.sup.2 to 5 mW/cm.sup.2, 5 mW/cm.sup.2 to 10 mW/cm.sup.2, 15
mW/cm.sup.2 to 25 mW/cm.sup.2 or any irradiance in a range bounded
by, or between, any of these values. Preferably, the power density
used to treat target cells or target tissue is of 0.05 to 30
mW/cm.sup.2, preferably of 15 to 25 mW/cm.sup.2, preferably of 20
to 25 mW/cm.sup.2 and more particularly of 23 mW/cm.sup.2.
[0085] More generally, the irradiation of blue light performed in
this method may be set using all the different values of fluence,
power intensity and time described above for the light source
device 10 and the light source assembly.
[0086] This method allows to benefit from the same effects as
described above for the light source device 10 and the light source
assembly. Particularly, the present method allows to obtain the
unexpected technical effect of blue light consisting in inducing or
promoting growth and proliferation of cells or tissue.
[0087] In particular, the method according to the invention is very
useful for growth and proliferation of skin cells, such as cells of
epidermis and/or dermis, such as keratinocytes or fibroblasts,
preferably keratinocytes.
[0088] The present invention also describes a light source device
for use for the in vivo growth and proliferation of cells or
tissue, preferably skin cells or tissue, such as keratinocytes or
fibroblasts. Preferably, the light source device is according to
the present invention.
[0089] The present invention also describes a light source assembly
containing a light source device for use for the in vivo growth and
proliferation of cells or tissue, preferably skin cells or tissue,
such as keratinocytes or fibroblasts. Preferably, the light source
assembly is according to the present invention.
[0090] The invention will be illustrated further by the following
examples:
Example 1: Effect of the Blue Light on the Growth and Proliferation
of Keratinocytes
Cell Culture
[0091] Keratinocytes (HaCaT, Immortal Human Keratinocyte in
Dulbecco's Modified Eagle Medium, from CLS Company) were incubated
in 96 multi-well plates.
[0092] The concentration of cells was about 2.5.times.10.sup.4
cells/well. 48 hours after cell incubation, cells were washed with
a phosphate buffered saline (PBS) solution.
[0093] Then, the wells containing the keratinocyte cells are
treated by a blue light.
Light Treatment
[0094] For the light treatment Lumileds Luxeon Rebel LXML-PR01-0275
from Koninklijke Philips N.V. (Eindhoven/Netherlands) was used. The
plates were irradiated from a distance of 5 cm with a power density
of 23 mW/cm.sup.2. The beam divergence was .+-.15.degree. with a
dominant emission wavelength of 453 nm (blue light).
[0095] The keratinocyte wells were irradiated with different energy
densities.
XTT Test (Measurement of the Keratinocyte Cell Proliferation)
[0096] The XTT Cell proliferation test is a well-known method for
the skilled person. For this test the Colorimetric Cell Viability
Kit III from PromoKine (Heidelberg/Germany) was used. For the test
50 .mu.L of labeling-mixture containing labeling reagent and
electron coupling reagent was mixed with cell suspension where the
XTT
(2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide)
is metabolized to water soluble formazan dye. Only viable cells
have the ability to metabolize, hence the formazan is used to
directly quantify the proliferation measured by spectrophotometric
absorption with Infinite.RTM. 200 PRO microplate reader from Tecan
Group AG. (Mannedorf/Switzerland).
Results
[0097] The cell proliferation of keratinocytes is illustrated in
the graph of FIG. 2. The graph represents the "fold change" in
function of the transmitted fluence with blue light irradiation to
the cells.
[0098] By "fold change", it means the ratio of proliferation with
blue light on the proliferation with non-irradiated cells
[0099] In order to evaluate the attenuation or absorption of the
light that can occur if the skin tissue is irradiated with blue
light, the loss of light power has been evaluated through a lid
(which reflects the light), a plate (culture wells which absorbs
the light) and a medium culture (4 mm of height for a volume of
about 1.5 mL).
[0100] The energy density (fluence) effectively received after
passing through the different elements listed above (lid, plate and
medium culture) was measured with a Power Meter.RTM. 843-R-USB from
Newport Corporation. A loss of 45% has been observed.
[0101] The graph of FIG. 2 and the zoom of FIG. 3 shows that the
exposure of keratinocytes to blue light (453 nm) with energy
densities of less than 18.5 J/cm.sup.2, promotes or induces
proliferation of keratinocytes which well shows that an irradiation
with blue light can be used for the treatment of wounds and
injuries. On the contrary, the exposure of keratinocytes to blue
light (453 nm) with energy densities higher than 18.5 J/cm.sup.2
inhibits proliferation of keratinocytes which and would therefore
not be suitable for the closure of wounds and injuries.
Example 2: Effect of the Blue Light on the Growth and Proliferation
of Fibroblasts
[0102] The same protocol as the one used in example 1 was used by
replacing the keratinocyte cells by fibroblast cells: Normal Human
Dermal Fibroblast (NHDF) in Dulbecco's Modified Eagle Medium
(available from PromoCell Company).
[0103] The cell proliferation of fibroblasts is illustrated in the
graph of FIG. 4. The graph represents the "fold change" in function
of the transmitted fluence with blue light irradiation to the
cells.
[0104] The graph of FIG. 4 shows that the exposure of fibroblasts
to blue light (453 nm) with energy densities of less than 18.5
J/cm.sup.2 promotes or induces proliferation of fibroblasts which
well shows that an irradiation with blue light can be used for the
treatment of wounds and injuries. On the contrary, the exposure of
fibroblasts to blue light (453 nm) with energy densities higher
than 18.5 J/cm.sup.2 inhibits proliferation of fibroblasts which
and would therefore not be suitable for the closure of wounds and
injuries.
* * * * *