Accelerating cutaneous healing utilizing non-invasive focused ultrasound
The present approaches are generally directed to facilitating healing of wounds, including chronic wounds typically associated with slow heal times or which are persistent. In one embodiment, a method of promoting wound healing comprises positioning an ultrasound transducer at a stimulation site on a subject having a wound. Pulsed focused ultrasound (pFUS) is non-invasively applies using the transducer to cause modulation of a target anatomic site containing resident or circulating immune cells. Modulation of the target anatomic site of the subject causes migration of one or more of monocytes, macrophages, or neutrophils to a wound bed of the wound.
1 . A method of promoting cutaneous wound healing, comprising:
positioning an ultrasound transducer at a stimulation site on a subject having a cutaneous wound;
non-invasively applying pulsed focused ultrasound (pFUS) using the transducer to cause modulation of a target anatomic site that is on or within an internal organ, wherein the target anatomic site contains or regulates resident or circulating immune cells; and
wherein modulation of the target anatomic site of the subject causes migration of one or more of monocytes, macrophages, or neutrophils to a wound bed of the cutaneous wound.
2 . The method of claim 1 , wherein the stimulation site is distal from the wound.
3 . The method of claim 1 , wherein the target anatomic site is a spleen of the subject and wherein the non-invasively applied pulsed focused ultrasound stimulates nerve pathways within the spleen.
4 . The method of claim 1 , wherein modulation of the target anatomic site alters concentrations of systemic circulating pro-inflammatory molecules.
5 . The method of claim 4 , wherein the pro-inflammatory molecules comprise TNFα and IL-6.
6 . The method of claim 1 , wherein applying pulsed focused ultrasound to the target anatomic site of the subject comprises applying pulsed focused ultrasound to the spleen of the subject at least once a day over a treatment interval.
7 . The method of claim 1 , wherein the pulsed focused ultrasound (pFUS) applied to the target anatomic site has parameters of a pulse center frequency of 1.1 MHz, a pulse repetition period of 0.5 msec, a 150 cycle burst, a burst period of 200 msec, and an aggregate duration of 3 or more minutes.
8 . The method of claim 1 , wherein applying pulsed focused ultrasound (pFUS) to the spleen of the subject accelerates wound closure by 3 to 5 days relative to no treatment.
9 . The method of claim 1 , wherein the target anatomic site is the spleen and wherein IL-6 levels are reduced in the spleen in response to applying the pulsed focused ultrasound (pFUS) to the spleen.
10 . The method of claim 1 , wherein L-selectin levels are higher in the wound bed of the wound in response to applying the pulsed focused ultrasound (pFUS) to the target anatomic site.
11 . The method of claim 1 , wherein one or both of anti-inflammatory cytokines or proteins associated with wound healing increase in one or both of the spleen of the subject or the wound bed.
12 . The method of claim 1 , wherein modulation of the target anatomic site of the subject modulates invasiveness of one or more types of circulating immune cells.
13 . The method of claim 1 , wherein a first pulsed focused ultrasound (pFUS) is applied to the target anatomic site of the subject within 24 hours of the wound forming.
14 . A system for promoting cutaneous wound healing, comprising:
a function generator configured to produce a pulsed sinusoidal waveform;
an RF power amplifier configured to amplify the pulsed sinusoidal waveform;
a matching network configured to receive the amplified pulsed sinusoidal waveform; and
a transducer connected to the matching network and configured to generate focused ultrasound pulses based upon the amplified pulsed sinusoidal waveform;
wherein the system is configured to, upon placement of the transducer at an external stimulation site of a subject, direct focused ultrasound pulses toward a target anatomic site that is on or within an internal organ, wherein the target anatomic site contains or regulates resident or circulating immune cells; and
wherein modulation of the target anatomic site of the subject causes migration of one or more of monocytes, macrophages, or neutrophils to a wound bed of a cutaneous wound.
15 . The system of claim 14 , wherein the focused ultrasound pulses have a pulse center frequency of 1.1 MHZ, a pulse repetition period of 0.5 msec, a 150 cycle burst, a burst period of 200 msec, and an aggregate duration of 3 or more minutes.
16 . The system of claim 14 , wherein the target anatomic site is a spleen of the subject and wherein non-invasively applied pulsed focused ultrasound stimulates nerve pathways within the spleen.
17 . The system of claim 14 , wherein modulation of the target anatomic site alters concentrations of systemic circulating pro-inflammatory molecules.
18 . The system of claim 14 , wherein one or both of anti-inflammatory cytokines or proteins associated with wound healing increase in one or both of the spleen or wound bed.
19 . The system of claim 14 , wherein modulation of the target anatomic site of the subject modulates invasiveness of one or more types of circulating immune cells.
20 . A method of promoting cutaneous wound healing, comprising:
positioning an ultrasound transducer at a stimulation site on a subject having a cutaneous wound;
non-invasively applying pulsed focused ultrasound (pFUS) using the transducer to cause modulation of a target anatomic site that is on or within an internal organ, wherein the target anatomic site contains or regulates resident or circulating immune cells; and
wherein modulation of neurons within the target anatomic site causes a phenotype change of one or more of leukocytes, monocytes, macrophages, or neutrophils that alter healing of a distal wound bed of the cutaneous wound.