Photothermal Biostimulation of Platelet-Rich Plasma Improves Hand Rejuvenation Clinical Outcome: A Pilot Study

Abstract

Objective:

This study aimed to evaluate physical skin changes and patients’ subjective perception of treatment with photothermal bioactivated platelet-rich plasma (MCT Plasma) for hand rejuvenation.

Background:

Age-related changes in the dorsum of the hand include volume loss, dyschromia, and soft-tissue atrophy, which result in wrinkles and prominent deep structures.

Methods:

We conducted a prospective, single-center, randomized pilot study on 10 healthy female volunteers from 30 to 65 years with hand aging signs. Patients received two sessions of MCT Plasma on the treated hand and two sessions of standard platelet-rich plasma (PRP) on the control hand. Results were assessed through high-frequency ultrasonography, photographs, a patient satisfaction survey, patient perception of skin aspect, and patient perception of amelioration survey.

Results:

Ten women with a mean age of 57.5 years (standard deviation 10.5, range 31 − 67) were included, and seven (70%) completed the study. The treated hands’ skin subepidermal low-echogenic band (SLEB) decreased from 20% to 60%, and 57.1% (n = 4) had better results than control. Twenty percent of patients were very satisfied with the results, 40% were satisfied, 40% were neutral, and none were unsatisfied or very unsatisfied. Patients perceived the skin of the treated hand (MCT Plasma) as “much better” (20%), “better” (60%), and “no changes” (20%) compared with the skin of the control hand (standard PRP). No treatment-related adverse events were reported during the study.

Conclusions:

Hands treated with MCT Plasma tended to have better outcomes in reducing SLEB compared with those treated with standard PRP. Patients were satisfied and the treatment was safe with no technical complications. However, further randomized controlled trials with larger sample sizes are mandatory to validate the extent of improvement provided by this device based on photothermal biomodulation.

Introduction

Skin aging results from an intrinsic process involving genetic background and an extrinsic process influenced by environmental factors.¹ Age-related changes on the hand dorsum are volume loss, dyschromia, and soft-tissue atrophy, resulting in wrinkles, and prominent deep structures.² Many anti-aging cosmetic products and other minimally invasive, safe, and effective treatments are used to prevent and treat it.³ Intradermal injection of platelet-rich plasma (PRP) is an example of these treatments, which have significant results,⁴ high patient satisfaction, and no serious adverse effects.⁵ A novelty related to PRP is using light and temperature to prime and stimulate platelets, producing photothermal biostimulated or biomodulated PRP, also known as MCT Plasma.^6,7

Photobiomodulation (PBM) therapy, first identified and named in the late 19th century,⁸ can produce stimulatory, inhibitory results, and no effects, depending on the dose used, resulting in the so-called biphasic dose-response curve.⁹ The principles of the biphasic response state that a shallow light dose has no effect, and a slightly higher dose produces a beneficial effect until a threshold is reached.¹⁰ If the light dose is increased beyond this point, the benefit decreases until the baseline (no effect) is reached. Further increases will harm the tissue.^9
–11

PBM has a biostimulatory effect that triggers multiple factors and contributes to several processes,^12,13 such as the increase in adenosine triphosphate and nitric oxide.¹⁴ However, these beneficial properties can only be achieved when PBM is applied smartly, considering the specific response of each tissue or cell type to adapt it to a tailored therapeutic window.¹⁰

In PBM, finding the proper parameters and application time are mandatory integration exercises to achieve clinical results and biological benefits. Wavelengths have shown an effective optical window that runs from about 600 nm to 1200 nm, restricting the use of PBM in humans to red and infrared lights almost exclusively.¹⁵ The energy applied to cells in PBM treatments can range from 0.1 J/cm² to 7.5 J∕cm², with 1 J/cm² and 5 J/cm² sweet spots.¹⁶ Power densities at the site usually range from 0, 1.67 mW∕cm² to 12.5 mW∕cm² since the energy is usually delivered in 10 min.

Like light, temperature affects organisms, tissues, and cells differently. Thermal biomodulation (TBM) is a new concept,⁷ easily understandable, that can modulate cell biological activity through heat or cold. TBM contributes to several biological processes, including vasodilation, alteration of rheological properties, and platelet kinetics, among many others.

PBM and TBM are stand-alone treatments, but they can also be used as ancillary procedures to enhance the effectiveness of other therapeutic procedures, such as PRP. It has already been established that TBM enhances the efficacy of PRP, and several studies have aimed at optimizing PRP protocols through different optimizing strategies.⁶ These studies set the basis for MCT Plasma at 4°C. They reached essential conclusions, including that, though PRP is usually processed at 37°C or room temperature (20°C–25°C), lower temperatures enhance platelet performance.⁶ The release of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF) has also been reported when PRP is obtained at 4°C.⁶ Few studies have addressed the TBM issue but reported consistent results and achieved statistically significantly higher EGF, bFGF, and VEGF concentrations after TBM protocols.⁷ Other groups have concluded that TBM is a novel and convenient method for preparing and activating PRP without additives.¹⁷

This study aimed to evaluate physical skin changes and patients’ subjective perception of treatment with MCT Plasma (photothermal biostimulated PRP) and compared it with standard PRP for hand rejuvenation.

Methods

Study design

We conducted a prospective, single-center, randomized pilot study on 10 healthy female volunteers of age 30 to 65 with hand aging signs. The study was carried out at TClinic Toledo from October 2022 to November 2023. Patients received two mesotherapy MCT Plasma sessions in one hand with different stimulation procedures, and the control hand received two treatment sessions with standard PRP.

Exclusion criteria included pregnancy or breastfeeding, malignancy, viral infection (Hepatitis B, Hepatitis C, AIDS, and syphilis serology, discarded through a blood analysis), systemic autoimmune or blood diseases, treatment for hand rejuvenation in the 2 months prior to the study, and treatment with immunosuppressants or anticoagulants.

Study design and procedures

Patientś hands were assigned by simple randomization. The first and second MCT Plasma sessions were administered 195 ± 15 days apart. Results were assessed through high-frequency ultrasonography (HF-USG), photographs, patient satisfaction survey, patient perception of skin aspect, and patient perception of amelioration against control survey, assessed 30 days after each session (Fig. 1).

FIG. 1.

Study flowchart.

PRP preparation and photothermal biostimulation

A 10-mL sample of peripheral blood was obtained from each patient. Samples were centrifuged with a Nahita 2610 (Beriain, Spain) at 1500 rpm for 10 min and concentrated according to PRP preparation standards. For both sessions, one and a half of the PRP was converted to MCT Plasma with the MCT System (Metacell Technology^®, Sant Cugat, Spain), and the other half was not (standard PRP), serving as control (Fig. 2). MCT Plasma was carried out according to the protocol provided by the manufacturer. Samples were poured into sterile, single-use MCT Kits^® (Metacell Technology^®, Sant Cugat, Spain) and then inserted in the MCT Unit^® (Metacell Technology^®, Sant Cugat, Spain). For the first session, treatment samples (MCT Plasma−I) were submitted to 0.2 J/cm² at 623 nm for 10 min and at 4°C for 15 min through a light emitting diode (LED) with a focal distance of 1 cm and forced air cooling (Fig. 2). For the second session, treatment samples (MCT Plasma−II) were submitted to 1 J/cm² at 623 nm for 10 min and at 4°C for 15 min (Fig. 2). The absolute maximum ratings and the typical electrical and optical characteristics of the LED as the light source employed for the PRP biostimulation are in Table 1 and Table 2.

FIG. 2.

Setup to obtain photothermal biomodulated platelet-rich plasma with the MCT System. MCT, photothermal biomodulated paltelet-rich plasma.

Table 1.

The Absolute Maximum Ratings of the Light Emitting Diode (LED) as Light Source Employed for the Platelet-Rich Plasma Biostimulation

Parameter	Symbol	Absolute maximum rating of LED			Unit
Parameter	Symbol	Red	Green	Blue	Unit
Forward current	I_F	25	20	20	mA
Pulse forward current^a	I_FP	80	80	80	mA
Reverse voltage	VR	5	5	5	V
Operating temperature	T_OPR	−30∼85			°C
Storage temperature	T_stg	−40∼100			°C
Power dissipation	P_D	60	72	72	mW
Electrostatic discharge (HBM)	ESD	1000 V

Pulse width ≦0.1 msec, duty ≦1/10. °C, degree Celsius; LED, light emitting diode; mA, milliampere; mW, milliwatt; V, volts.

Table 2.

The Typical Electrical and Optical Characteristics (Ts = 25°C) of the Light-Emitting Diode (LED) as the Light Source for the Platelet-Rich Plasma Biostimulation

Parameter	Symbol	Condition	Electrical and optical characteristics values			Unit
Parameter	Symbol	Condition	Red	Green	Blue	Unit
Reverse Current (max)	I_R	V_R = 5 V	6	6	6	μΑ
Forward voltage	V_F(min)	I_F = 20 mA	1.7	2.7	2.7	V
Forward voltage	V_F(max)	I_F = 20 mA	2.4	3.4	3.4	V
Dominant wavelength	λ_D	I_F = 20 mA	618∼628	518∼528	464∼474	nm
Spectrum radiation bandwidth	Δλ	I_F = 20 mA	24	38	30	nm
Luminous intensity	IV (min)	I_F = 20 mA	500	1200	280	mcd
Luminous intensity	IV (avg)	I_F = 20 mA	650	1500	380	mcd
50% power angle	2θ½	I_F = 20 mA	110			deg

Tolerance of measurement of luminous intensity: ±10%.

Tolerance of measurement of dominant wavelength: ±1 nm.

Tolerance of measurement of forward voltage: ± 0.05 V.

deg, degree; IF, forward current; μΑ, microampere; mA, milliampere; mcd, millicandela; nm, nanometers; V, volts.

Injection technique

In all treatment sessions the skin of both hands was cleaned with saline solution and chlorhexidine, and a topical anesthetic lidocaine-prilocaine cream (EMLA Cream) was applied for 20 min. All samples (MCT Plasma and standard PRP) were administered using a mesotherapy technique (0.05 ml per prick, 30G½ needle, 2.0-mm depth). After treatment, a soothing cream was applied to the treated area. The complete intervention lasted from 10 to 15 min.

Outcome measures

At baseline and 30 days after each treatment session, the skin subepidermal low-echogenic band (SLEB) width was measured using an HF-USG with an Alpinion E-cube i7 and a 3 − 12-Mhz linear transducer (Alpinion Medical System; Seoul, Korea). SLEB thickness and echogenicity are correlated with photoaging and inflammatory processes at the skin level and with the accumulation of water molecules (edema).¹⁸ Photographs were taken with a Sony ILCE-5100 camera.

Thirty days after each treatment session, patients were asked about their satisfaction with treatment through a 5-point Likert scale, with the following possible answers: “very satisfied,” “satisfied,” “neutral,” “unsatisfied,” or “very unsatisfied.” Patients were also asked, after treatment, about their subjective perception of the treated hand (MCT Plasma) skin aspect and amelioration compared with the control hand (standard PRP) through a 5-point Likert scale, with the following possible answers: “much better,” “better,” “no changes perceived,” “worse,” or “much worse.”

Safety measures

All information regarding possible complications and adverse events (AEs) during the intervention was collected.

Statistical analysis

Quantitative variables were described as the mean and standard deviation (SD), whereas categorical variables were described as frequencies or percentages. Efficacy outcomes were assessed as the percentage of change of the corresponding variable from baseline to 30 days after the last treatment session. The statistical significance of changes after treatment was calculated using the comparison of proportions calculator by MedCalc Software Ltd. Only patients who completed all treatment sessions were considered for statistical analysis.

Results

Ten women with a mean age of 57.5 years (SD 10.5, range 31 − 67) were enrolled, and seven (70%) completed the study with a mean age of 57.0 years (SD 12.1, range 31 − 67). Patient dropouts were due to lack of follow-up, not due to AEs or disagreement with the procedures. All hands in the treatment group showed a reduction in SLEB, with an average reduction of 44.76% and a maximum reduction of 60%; in the control group, the average reduction was 34.1% with a maximum decrease of 62% (p = 0. 6345). In two hands of the control group (28.6%), no change occurred after treatment, and in 2 (28.6%) hands, the SLEB decrease was lower. SLEB measurements at baseline and 30 days after the first and second treatment sessions are detailed in Table 3. Photographs and echography images of a representative patient, taken at baseline and after the two treatment sessions, are shown in Figure 3. No treatment-related AEs occurred during the study. Fourteen percent of patients “were very satisfied” with the treatment after the first session and 29% after the second (Fig. 4). Fifty-seven percent of patients had subjective skin amelioration of better after the first session, and 71% had this perception after the second session (Fig. 4). However, these variations were not statistically significant.

Table 3.

Echography Assessment. Session I: MCT Plasma−I (PRP Photothermal Biostimulation of 0.2 J/cm2 at 623 nm for 10 Min and at 4°C for 15 Min). Session II: MCT Plasma−II (PRP Photothermal Biostimulation of 1 J/cm2 at 623 nm for 10 Min and at 4°C for 15 Min). Control Sessions I and II: standard PRP

Treated hand (MCT plasma)					Control hand (standard PRP)
Patient	BAS (mm)	Session I (mm)	Session II (mm)	Diff ^a(%)	BAS (mm)	Session I (mm)	Session II (mm)	Diff ^a(%)
1	0.06	0.06	0.03	−50.00	0.08	0.05	0.03	−62.50
3	0.06	0.04	0.03	−50.00	0.04	0.04	0.04	0.00
6	0.05	0.05	0.04	−20.00	0.07	0.06	0.04	−42.86
7	0.06	0.05	0.03	−50.00	0.06	0.06	0.04	−33.33
8	0.05	0.03	0.02	−60.00	0.04	0.04	0.02	−50.00
9	0.03	0.03	0.02	−33.33	0.03	0.03	0.03	0.00
10	0.04	0.04	0.02	−50.00	0.06	0.04	0.03	−50.00
Mean	0.05	0.04	0.03	−44.76	0.05	0.05	0.03	−34.10
SD	0.01	0.01	0.01	13.45	0.02	0.01	0.01	24.88

From baseline to follow-up Session II.

BAS, baseline; mm, millimeters; %, percentage; SD, standard deviation.

FIG. 3.

Patient three photographs and images of high-frequency ultrasonography of hands at baseline and after 30 days of the treatment session II.

FIG. 4.

Percentage of patients by perception about treatment and skin aspect and amelioration.

Discussion

All hands treated with MCT Plasma showed decreases in the SLEB assessed through HF-USG with a 57.1% of better results than the control group. Only 71.4% of hands treated with standard PRP had measurable decreases. Patients were satisfied with the treatment results and visually appreciated changes in the surface of the hand. The treatment was safe without AEs.

In recent years, interest in hand rejuvenation has increased, specifically in the case of patients who underwent facial and neck aesthetic treatments since untreated hands may show a discrepancy with the appearance of the face.² Therapeutic options to improve the appearance of aging hands include chemical peels,¹⁹ laser therapy,²⁰ sclerotherapy, dermal fillers,²¹ and autologous fat transfer.²² PRP has also been used to treat skin aging of hands. In 2017, Cabrera-Ramírez et al. conducted a study to treat hand photodamage using PRP.²³ They made before and after histological comparisons applying PRP to the dorsum of the hands. Their results showed an increase in the number of fibroblasts, vessels, and collagen density with statistical significance.

In this study, we observed that the hands treated with MCT Plasma showed a higher decrease in SLEB width than in control hands (standard PRP). In addition, patients visually appreciated changes in their skin were satisfied and found that the amelioration of the dorsal hand skin was between “better” and “much better” than the control hand.

Witnessing the superior results that we have obtained in this small study, considering the outcome of other studies with standard PRP, and understanding the proven benefits of PBM make it obvious and necessary to face new and powerful protocols that can quantify this therapeutic improvement.

Study limitations include the low number of patients and the non-randomized design, which does not provide statistical robustness to our results. Other limitations include the difficulty of visually appreciating the skin changes, which made patients less satisfied with the results. This weakness is important because it makes us aware that the structural changes these treatments produce in the tissues must be clearly explained to patients before starting treatment. Further, throughout the treatment, we must be shown their effectiveness so that they understand that it is not an immediate aesthetic effect but rather that the treatment is acting at a molecular level, which may take time, and that the results will not be striking or immediate. Also, subjective tools for measuring the changes, such as some satisfaction survey questions, did not give us strong results. However, using objective instruments such as HF-USG to measure the SLEB enhanced our data’s reliability.

Potential future approaches to this technology might be addressed to cell priming and subcellular optimization to improve the regenerative power of orthobiologics. In this context, photothermal biomodulation has been proven to deliver remarkable clinical results and is moving forward as a safe and effective option. However, further research should be undertaken to provide and fine-tune new protocols to broaden its use, identifying new wavelengths, intensities, and modalities to increase photothermal biomodulation popularity and success.

Conclusion

Hands treated with MCT Plasma tended to have better outcomes in reducing SLEB compared to those treated with standard PRP. Patients were satisfied and the treatment was safe with no technical complications. However, further randomized controlled trials with larger sample sizes are mandatory to validate the extent of improvement provided by this device based on photothermal biomodulation.

Footnotes

Acknowledgments

The authors thank all study collaborators, especially the i2e3 Procomms medical writing team.

Authors’ Contributions

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work, and have given their approval for this version to be published. P.T.G., S.M.A., M.O.Z, R.L.M.S, and H.P. conceptualization, methodology, data acquisition, and analysis. P.T.G., and H.P. writing—original draft preparation, and writing—review and editing.

Author Disclosure Statement

P.T.G., S.M.A., M.O.Z., and R.L.M.S. have no conflicts of interest or financial ties to disclose. H.P. is a scientific consultant for MCT but has not received any fees for this study.

Ethics statement

The study was part of the post-marketing clinical monitoring plan of the medical device classified as IIa but was not evaluated by an ethics committee. However, the study was conducted according to the principles outlined in the revised Declaration of Helsinki and the Good Clinical Practice guidelines. The data collection and management process adhered to the laws protecting personal data and the free movement of such data.

Funding Information

The study did not receive any funding.

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