Clinical efficacy of intradermal type I collagen injections in treating skin photoaging in patients from high-altitude areas

Abstract

BACKGROUND

Photoaging, a result of chronic sun exposure, leads to skin damage and pigmentation changes. Traditional treatments may have limitations in high-altitude areas like Yunnan Province. Intradermal Col Ι injections stimulate collagen production, potentially improving skin quality. This study aims to assess the efficacy and safety of this treatment for photoaging.

AIM

To evaluate the efficacy and safety of intradermal type Ι collagen (Col Ι) injection for treating photoaging.

METHODS

This prospective, self-controlled study investigated the impact of intradermal injections of Col Ι on skin photodamage in 20 patients from the Yunnan Province. Total six treatment sessions were conducted every 4 wk ± 3 d. Before and after each treatment, facial skin characteristics were quantified using a VISIA skin detector. Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector. The Face-Q scale was used for subjective evaluation of the treatment effect by the patients.

RESULTS

The skin thickness of the right cheek consistently increased after each treatment session compared with baseline. The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline. The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions, whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions. The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline (P < 0.05). These findings were also supported by skin ultrasound images. The feature count for the red areas and wrinkle feature count decreased following the treatment (P < 0.05). VISIA assessments also revealed a decrease in the red areas after treatment. The Face-Q-Satisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session. The overall appearance of the patients improved after treatment.

CONCLUSION

Intradermal Col Ι injection improves photoaging, with higher patient satisfaction and fewer adverse reactions, and could be an effective treatment method for populations residing in high-altitude areas.

Key Words: Photoaging; Type Ι collagen; Face-Q; High-altitude area; Skin photodamage; Patient satisfaction

Core Tip: Intradermal injections of type I collagen show promise in improving skin quality and treating photoaging in high-altitude regions like Yunnan. Using a negative pressure electronic injection device, the treatment enhances skin thickness, reduces redness and wrinkles, and leads to high patient satisfaction with minimal adverse effects. This approach addresses key manifestations of photoaging in high-altitude populations and could provide an effective, minimally invasive therapeutic option.

INTRODUCTION

Skin photoaging, also known as exogenous aging, is mainly caused by ultraviolet (UV) radiation, which accounts for 80% of the skin-aging-inducing external factors[1]. UV radiations damage the structure and function of collagen (Col; I and III), the major component of the dermal layer, and accelerate skin aging through a series of complex molecular and cellular mechanisms[2-5]. Clinically, its manifestations include skin dryness and roughness, capillary dilation, increased wrinkles, reduced elasticity, and pigmentation. Notably, some patients may develop skin tumors, manifesting as thinning of all levels of the skin and changes in skin structure, accompanied by decreased synthesis and proliferation and changes in the Col I and III ratio in the extracellular matrix (ECM) of the dermis layer[6]. Currently, plant-derived anti-photoaging formulations[7-9], vitamin supplementation[10], chemical peel treatments, laser therapy[11,12], radiofrequency microneedle therapy[13], injectable treatments[14], and surgical interventions are employed as preventive and therapeutic measures for cutaneous photoaging, including sun protection. Our study introduces an innovative approach utilizing the Derma Shine Generation I negative pressure electron injection device for Sunmax Col I intradermal injections in patients with cutaneous photoaging from high-altitude regions. Further, various evaluation methods were employed to assess treatment outcomes.

MATERIALS AND METHODS

Study participants

The study has obtained ethical approval from the Ethics Committee of the First People's Hospital of Kunming City and signed informed consent forms. enrolled 20 patients who sought treatment for skin photoaging at our department between June 2021 and April 2022 and met the inclusion and exclusion criteria (Table 1). Among them, 19 were female (95%), and 1 was male (5%). The mean age was 46.4 years, ranging from 36 to 54 years.

Table 1 Inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
Age ≥ 18 yr, male or female	Pregnancy or lactation
Glogau photoaging score of II or III	Systemic diseases, such as diabetes, autoimmune diseases, and severe heart, liver, and kidney dysfunction
Residing in areas with an altitude of ≥ 1800 m for > 10 yr	Current treatment with glucocorticoids, estrogen, and other drugs that may cause facial pigmentation and affect the experimental results
Voluntarily receiving intradermal injection of Sunmax Col for facial rejuvenation and signing informed consent forms	Facial laser, freezing, and other treatments within the past 3 months
	Facial filling or botulinum toxin injection within the past 6 months
	Known allergies to Col or other ingredients in Sunmax Col
	Failure to follow up as planned or data loss affecting the evaluation of efficacy

Methods

Treatment procedure and precautions: In this study, we used a Derma Shine Generation I negative pressure electron injection device to administer a full-face Sunmax Col injection to all patients. The procedure was as follows: (1) After cleaning their skin, patients laid down in the supine position, and the operator applied topical anesthesia to their faces. After 30 min, the anesthesia was removed, and the faces of the patients were disinfected with an iodine III skin disinfectant; (2) A 2.5 mL of diluted Col mixture was prepared by the operator by mixing 1.5 mL of 0.9% normal saline (NS) with 1 mL of Sunmax Col (Furoumei) drawn using a disposable sterile syringe (2.5 mL), which was connected to a three-way tube for injection; (3) The operator wiped off the iodine from the faces of the patients using 0.9% NS; (4) The operator added a 2.5-mL Col mixture into the Derma Shine Generation I negative pressure electron injection device and set the parameters (dose per injection, 0.025 mL; injection speed, slow; negative pressure suction, 10%; and retraction force, 80%). Next, the operator injected the mixture evenly into the face of the patient in the following order: bilateral cheeks, forehead, periorbital area, and perioral area. The injection depth for the cheeks was generally 0.8-1.0 mm, and that for the forehead, periorbital area, and perioral area was generally 0.6-0.8 mm. Notably, the injection depth was adjusted according to the skin condition and pain tolerance of the patient; and (5) After the procedure, the medical cold compressed masks were applied to the faces of the patients for 20 min. The patients were instructed to keep the treatment area clean, avoid massaging the treatment area, avoid high-temperature and humid environments, such as hot springs, and saunas, avoid sun exposure, and refrain from other facial cosmetic procedures, including botulinum toxin injection, chemical peeling, phototherapy, and facial filling. The patients could start washing their faces with water after 4 h and start using a facial cleanser 24 h following treatment.

Treatment effect evaluation (VISIA facial skin imaging analyzer and Dermalab SkinLab Combo ultrasound): For objective evaluation, we used a VISIA facial skin imaging analyzer and a Dermalab SkinLab Combo ultrasound probe to collect objective data from the patients[15,16]. Each patient received six treatments, with an interval of 4 wk ± 3 d between treatments. Before treatment and 2 wk ± 3 d after each treatment, eight indicators of facial skin quality—surface spots, wrinkles, texture, pores, UV spots, brown spots, red areas, and porphyrins—were analyzed using the VISIA facial skin imaging analyzer. The Dermalab SkinLab Combo ultrasound probe indirectly reflects the density of the subcutaneous Col, enabling the measurement of the skin thickness of the bilateral cheeks, temporal regions, and malar regions.

Face-Q scale self-evaluation: For the subjective evaluation, we selected seven Face-Q subscales: Face-Q-Satisfaction with Facial Appearance Overall, Face-Q-Satisfaction with Skin, Face-Q-Satisfaction with Outcome, Face-Q-Satisfaction with Decision, Face-Q-Social Function, Face-Q-Psychological Function, and Face-Q-Adverse Effects: Skin. The patients self-evaluated Face-Q-Satisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin before treatment and 2 wk ± 3 d after each treatment. Further, the patients were followed up, and the evaluation of the Face-Q-Adverse Effects: Skin was also performed. Face-Q-Satisfaction with Outcome, Face-Q-Satisfaction with Decision, Face-Q-Social Function, and Face-Q-Psychological Function evaluations of all patients were completed after six treatments. Except for the Face-Q Adverse Effects: Skin scale, all other scales range from 0 to 100. A higher score indicates a better outcome (Table 2).

Table 2 Face-Q scale content.

Scale name	Content
Face-Q-Satisfaction with Facial Appearance Overall	Evaluates overall facial appearance
Face-Q-Satisfaction with Skin	Evaluates facial skin texture, color, and overall appearance
Face-Q-Satisfaction with Outcome	Evaluates the results of facial cosmetic treatments
Face-Q-Satisfaction with Decision	Evaluates decision-making regarding facial cosmetic treatments
Face-Q-Social Function	Evaluates the impact of facial appearance on social interactions
Face-Q-Psychological Function	Evaluates the psychological impact of facial appearance
Face-Q-Adverse Effects: Skin	Evaluates adverse reactions of the facial skin after treatment

Statistical analysis

Pairwise comparisons between the post- and pre-treatment data after six treatments were performed using paired-sample t-tests to compare the VISIA feature counts, skin thickness, and FACE-Q scales. SPSS 27.0 software was used to analyze the data. P < 0.05 was considered statistically significant.

RESULTS

Comparison of skin thickness before and after treatment

In this study, 20 patients received six treatments each. Notably, the skin thickness of the right cheek increased after each treatment compared with baseline, whereas the skin thickness of the left cheek increased after the third to sixth treatments compared with the previous treatments. The skin thickness of the right zygomatic area increased after the second to sixth treatments compared with the previous treatments, whereas the skin thickness of the left zygomatic area increased after the fourth to sixth treatments compared with the previous treatments. The skin thickness of both temporal areas increased after the fifth and sixth treatments compared with the previous treatments. All differences were statistically significant (P < 0.05). No statistically significant changes in skin thickness were observed for the rest of the treatments (P > 0.05). Skin ultrasound images showed that skin thickness increased after six treatments compared with baseline (Figure 1 and Table 3).

Figure 1 Skin ultrasound images. Dermalab SkinLab Combo ultrasound probe can be used to obtain skin cross-sectional images and skin thickness values based on different sound level signals. The brighter the color in the image, the greater the density of the area, which indirectly reflects the density of subcutaneous collagen. Skin ultrasound images showed that the skin thickness increased after six treatments compared with baseline. A: Before treatment; B: After the first treatment; C: After the second treatment; D: After the third treatment; E: After the fourth treatment; F: After the fifth treatment; G: After the sixth treatment.

Table 3 Comparison of skin thickness before and after intradermal injection of Col I (mm, mean ± SD).

	Baseline	1st	2nd	3rd	4th	5th	6th
Right cheek	1.65 ± 0.19	1.76 ± 0.22a	1.88 ± 0.19a	1.98 ± 0.16a	2.04 ± 0.15a	2.11 ± 0.17a	2.15 ± 0.20a
Left cheek	1.62 ± 0.21	1.69 ± 0.21	1.78 ± 0.19	1.90 ± 0.17a	1.99 ± 0.12a	2.06 ± 0.13a	2.12 ± 0.16a
Right zygomatic	1.57 ± 0.18	1.67 ± 0.20	1.79 ± 0.18a	1.89 ± 0.16a	1.96 ± 0.15a	2.02 ± 0.14a	2.08 ± 0.17a
Left zygomatic	1.56 ± 0.22	1.63 ± 0.24	1.75 ± 0.23	1.86 ± 0.20	1.94 ± 0.18a	2.01 ± 0.16a	2.05 ± 0.15a
Right temple	1.48 ± 0.25	1.54 ± 0.26	1.63 ± 0.24	1.75 ± 0.21	1.86 ± 0.18	1.96 ± 0.17a	2.00 ± 0.20a
Left temple	1.44 ± 0.24	1.52 ± 0.25	1.62 ± 0.26	1.73 ± 0.23	1.83 ± 0.20	1.94 ± 0.18a	1.99 ± 0.16a

^aP < 0.05, a statistically significant difference compared with before treatment.

Comparison of VISIA parameters before and after treatment

The redness feature count decreased after each of the six treatments compared with baseline (P < 0.05), and redness improved after each treatment compared with the previous treatment (Figure 2 and Table 4). The wrinkle feature count decreased after the sixth treatment compared with the previous treatment (P < 0.05), whereas the other parameter feature counts did not show any statistically significant changes (P > 0.05).

Figure 2 Facial photographs and associated redness feature maps of four participants. The images illustrate the condition of the face before treatment, after the third treatment, and after the sixth treatment. Notably, red zone counts decreased after each treatment compared with baseline. A: A 52-year-old female patient. The redness feature maps show a clear reduction in facial redness from before treatment to after the 3^rd and 6^th treatments; B: A 49-year-old female patient. Similar to patient A, the redness feature maps demonstrate a progressive decrease in facial redness following the 3^rd and 6^th treatment sessions compared to baseline; C: A 46-year-old female patient. The redness feature maps reveal a noticeable decline in facial redness after the 3rd treatment, with further improvement seen after the 6^th treatment; D: A 51-year-old male patient. Consistent with the female patients, the male patient's redness feature maps illustrate a gradual reduction in facial redness from before treatment to following the 3^rd and 6^th treatment sessions.

Table 4 Comparison of VISIA parameters before and after intradermal injection of type I collagen (feature count, mean ± SD).

	Baseline	1st	2nd	3rd	4th	5th	6th
Red area	374.55 ± 22.89	325.25 ± 22.92a	283.60 ± 23.08a	244.35 ± 25.81a	212.70 ± 28.48a	189.85 ± 28.52a	174.90 ± 27.18a
Wrinkles	118.40 ± 16.43	114.80 ± 16.26	111.60 ± 16.64	108.80 ± 16.39	106.45 ± 16.21	104.30 ± 15.48	102.20 ± 15.29a

^aP < 0.05, a statistically significant difference compared with before treatment.

Face-Q scale assessment

The scores of Face-Q-Satisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin increased after each of the six treatments compared with baseline (P < 0.01; Figures 2 and 3, Table 5). The scores of Face-Q-Satisfaction with Outcome, Face-Q-Satisfaction with Decision, Face-Q-Social Function, Face-Q-Psychological Function, and Face-Q-Adverse Effects: Skin were 67.05 ± 15.50, 83.8 ± 14.50, 76.5 ± 8.7, 78.75 ± 7.5, and 13.85 ± 3.82, respectively (Table 6). The overall appearance of the patients improved after treatments.

Figure 3 Redness feature counts and Face-Q satisfaction scores before and after treatment. A: Trend of the red area feature count before and after treatment. The graph shows the trend in the mean counts of redness features before and after treatment for the 20 subjects with a blue line, while solid dots are used to represent the mean counts at each treatment time point; B: Trends of Face-Q facial appearance satisfaction and skin satisfaction scores before and after treatment. The graph shows the trend of the Face-Q Satisfaction with Facial Appearance mean scores of 20 subjects before and after treatment in blue, and the trend of the Face-Q Satisfaction with Skin mean scores of 20 subjects before and after treatment in orange. The solid dots indicate the mean scores at each treatment time point.

Table 5 Comparison of Face-Q-Satisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores before and after intradermal injection of type I collagen (mean ± SD).

	Baseline	1st	2nd	3rd	4th	5th	6th
Face-Q-Satisfaction with Facial Appearance Overall	40.05 ± 15.03	49.50 ± 14.86a	57.50 ± 14.14a	64.50 ± 12.47a	72.50 ± 10.47a	76.50 ± 9.56a	80.40 ± 8.16a
Face-Q-Satisfaction with Skin	34.05 ± 11.98	45.5 ± 12.33a	55.25 ± 11.91a	63.5 ± 9.73a	73.6 ± 8.69a	78.35 ± 8.11a	82.40 ± 6.72a

^aP < 0.01, a statistically significant difference compared with before treatment.

Table 6 Face-Q-Satisfaction with Outcome, Face-Q-Satisfaction with Decision, Face-Q-Social Function, Face-Q-Psychological Function, and Face-Q-Adverse Effects: Skin scores after 6 intradermal injections of type I collagen (mean ± SD).

Scale	Score
Face-Q-Satisfaction with Outcome	67.05 ± 15.50
Face-Q-Satisfaction with Decision	83.8 ± 14.50
Face-Q-Social Function	76.5 ± 8.7
Face-Q-Psychological Function	78.75 ± 7.5
Face-Q-Adverse Effects: Skin	13.85 ± 3.82

DISCUSSION

In this study, we enrolled 20 patients living in high-altitude areas for a long time, with Glogau scores of II or III. All the enrolled patients received six treatments and completed all follow-ups. We employed subjective and objective assessment methods to observe the efficacy and safety of the Derma Shine Generation I negative pressure electron injection device for Col I intradermal injections for treating facial cutaneous photoaging in people living in high-altitude regions[17]. We aimed to identify an efficient and cost-effective treatment approach for facial cutaneous photoaging in people living in high-altitude areas. Dermal fillers, such as hyaluronic acid, Col, and other filling materials, can replenish the lost soft tissue volume of the skin and are increasingly used in the treatment of skin photoaging to reduce wrinkles and fine lines of facial skin[18-20]. Currently, microneedle introduction and manual injection are effective methods of Col administration[21]; however, they require operators with operational expertise and clinical experience, and the treatment effects and adverse reaction rates may vary substantially across operators. Consequently, to overcome these problems, we used the Derma Shine Generation I negative pressure electron injection device for the pharmaceutical preparation of Col in this experiment. Using this method, the injection depth, dosage, and speed can be kept consistent, facilitating a more uniform and comfortable injection, ensuring that Col is injected into the dermis, and reducing the wastage of Col reagents. Based on the currently known mechanisms of skin photoaging, we speculated that the mechanisms underlying the improvement in redness, skin thickness, and wrinkles following Col Ι intradermal injection may be as follows: Col Ι in the dermal ECM may be directly replenished, and the dermal layer exhibited a micro-filling effect, thereby increasing the mechanical interaction between fibroblasts and ECM and inhibiting further decline of fibroblasts, thus interrupting the positive feedback loop of accelerated aging of photoaged skin and inhibiting TGF-β signaling. The expression of matrix metalloproteinases decreased; therefore, the synthesis and decomposition of Col increased, ECM content increased, skin thickness increased, expression of related cell inflammatory factors decreased, chronic inflammatory response of the skin was alleviated, and red areas were reduced[22,23]. Notably, a significant effect of Col injection on improving wrinkles has also been reported by various researchers[24].

However, in our study, wrinkles improved only after the sixth treatment was completed. The reasons for this may be as follows: First, we diluted Col Ι with NS to meet the injection conditions of the negative pressure electronic injector. Second, the injection method involved a uniform injection of the entire face, and the injection was not specifically targeted at the wrinkled area. Notably, the generation of wrinkles also depends on the facial expression of the patient. Therefore, to improve wrinkles, diluting Col and using a negative pressure electronic injection device is not as effective as manual injection of Col. For patients with photoaged skin and notable wrinkles, manual injection combined with electronic injection may achieve better results. Notably, red skin areas and melanin indicators of people in high-altitude areas are higher than those in plain areas[25,26]. Intradermal injection of Col I using a negative pressure electronic injector can improve the symptoms of skin photoaging. Therefore, this treatment method is more suitable for improving skin photoaging in patients living in high-altitude areas, where skin redness and thinning are the main clinical symptoms. Nevertheless, this study has some limitations. First, the sample size was small. Second, no control group could be set up because of the unwillingness of the patients. Third, skin histological examinations could not be performed because of the equipment and unwillingness of the patients. Studies with a larger sample size, refining the sample grouping, and adding more objective evaluation indicators should be conducted in the future to better generalize the experimental results. In summary, this study innovatively used a negative pressure electronic injection device to perform Col Ι intradermal injection to treat skin photoaging and used the patient-centered, more comprehensive, and high-reliability Face-Q scale for subjective evaluation of the treatment effect by the patient and VISIA and Dermalab SkinLab Combo ultrasound probe for objective evaluation of various skin data, offering a new avenue for the treatment of skin photoaging in people living in high-altitude areas.

Intradermal type I collagen injections offer several potential advantages over other preventive and therapeutic measures for cutaneous photoaging. Compared to topical plant-derived or vitamin formulations, injectable collagen may more directly replenish lost dermal collagen. Chemical peels and laser therapy primarily affect the epidermis with less impact on dermal thickness and ectracellular matrix composition. Radiofrequency microneedling and surgical interventions are more invasive with increased risk of adverse effects and downtime. While other injectable treatments like hyaluronic acid fillers can improve wrinkles, they do not directly replace depleted collagen. Intradermal collagen injections may therefore provide a minimally invasive, targeted approach to restoring dermal collagen content and thickness. However, further studies directly comparing intradermal collagen to other treatment modalities are needed to establish its relative efficacy and advantages.

CONCLUSION

The intradermal injection of Col I improved skin photoaging in patients from high-altitude areas, showing significant enhancement in facial erythema and skin thickness. The patients exhibited high satisfaction levels and minimal adverse reactions, suggesting that this treatment could be an effective method for treating photoaging in populations residing in high-altitude areas.