In vitro and in vivo Evaluation on the Safety and Efficacy of a Brand-New Intracutaneous Filler with α1-R-Collagen

Figures & data

Figure 1 Schematic figure illustrating the injection area.

Table 1 Facial Volume Loss Scale (FVLS)

Variation % vs Baseline
T7	T30	T90
−21.2%	−24.2%	−24.2%
			Subjects %
			T7	T30	T90
Improved (at least 1 grade)			70%	80%	75%
Not changed			30%	20%	25%
Worsened			0%	0%	0%

Notes: The system identifies 5 levels of severity based on the length, width, and depth of folds and creases as well as volume loss in the different facial zones as follows. Grade 1 Mild flattening or shadowing of one or more facial regions (including the cheek, temple, preauricular and periorbital areas). No prominent bony landmarks. No visibility of underlying musculature. Grade 2 An intermediate point between grade 1 and grade 3. Grade 3 Moderate concavity of one or more facial regions (including the cheek, temple, preauricular, and periorbital areas. Prominence of bony landmarks. May have visibility of underlying musculature. Grade 4 An intermediate point between grade 3 and grade 5. Grade 5 Severe indentation of one or more facial regions (including the cheek, temple, preauricular, and periorbital areas). Severe prominence of bony landmarks. Clear visibility of underlying musculature.

Table 2 Wrinkle Severity Rating Scale (WSRS)

Variation % vs Baseline
T7	T30	T90
−18.2%	−21.2%	−21.2%
			Subjects %
			T7	T30	T90
Improved (at least 1 grade)			65%	70%	65%
Not changed			35%	30%	35%
Worsened			0%	0%	0%

Notes: Grade 1 (absent): no visible nasolabial fold; continuous skin line. Grade 2 (mild): shallow but visible nasolabial fold with a slight indentation; minor facial feature. Grade 3 (moderate): moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched. Grade 4 (severe): very long and deep nasolabial folds; prominent facial feature; <2mm visible fold when stretched. Grade 5 (very severe): extremely deep and long nasolabial fold, detrimental to facial appearance; 2–4 mm visible V-shaped fold when stretched.

Table 3 Variation of Face Volume

Volume Variation	Subjects %
	T7	T30	T90
Very marked improvement (Δ > 1 cc)	35%	40%	40%
Marked improvement (1 cc ≤ Δ > 0.5 cc)	40%	50%	45%
Light improvement (0.5 cc ≤ Δ > 0.2 cc)	20%	5%	10%
Unchanged (Δ ≤ 0.2 cc)	5%	5%	5%

Figure 2 Gene expression analyses (qRT-PCR) in the treated FT-skin model were expressed as relative quantification (RQ) with respect to control. Statistical differences between mean values were determined with Student’s t-test followed by Welch’s correction. The symbols indicate a significant difference (P < 0.05) to the control (* for COLIV, ^# for AQP3, ^$ for CD44). */ ^# /^$ (P < 0.05); **/ ^##/ ^$$ (P < 0.01); ***/ ^$$$ (P < 0.01).

Figure 3 Representative image analysis of improvement of midface volume before treatment (T0), 7 days (T7), 30 days (T30) and 90 days after injection of the brand-new intracutaneous filler. The subject’s midface was evaluated by mean of Vectra H1.

Figure 4 Representative image analysis of improvement of nasolabial folds before treatment (T0), 7 days (T7), 30 days (T30) and 90 days after injection of the brand-new intracutaneous filler. The subject’s midface was evaluated by mean of Vectra H1.

Figure 5 Representative image analysis of improvement marionette lines before treatment (T0), 7 days (T7), 30 days (T30) and 90 days after injection of the brand-new intracutaneous filler. The subject’s midface was evaluated by mean of Vectra H1.

Table 4 Profilometry of Nasolabial Folds

Nasolabial Folds	Variation (%) versus T0
	T7	T30	T90
Ra (average roughness of the analyzed profile)	−15.1% *	−27.5% *	−16.9% *
Rt (wrinkles total height)	−18.1% *	−25.5% *	−14.5% *
Rv (wrinkles maximum depth)	−21.3% *	−25.1% *	−14% *

Note: *Holm-Sidak Adjusted Wilcoxon signed rank/t-test p<0.05 vs T0.

Table 5 Profilometry of Marionette Lines

Marionette Lines	Variation (%) versus T0
	T7	T30	T90
Ra (average roughness of the analyzed profile)	−16.1% *	−25.2% *	−15.7%
Rt (wrinkles total height)	−14.9%	−21% *	−11.9%
Rv (wrinkles maximum depth)	−3.3%	−22.9%	−14.8%

Note: *Holm-Sidak Adjusted Wilcoxon signed rank/t-test p<0.05 vs T0.

Table 6 Superficial and Deep Hydration Variations

Parameter	Variation (%) versus T0
	T7	T30	T90
Superficial skin hydration	+14.8%	+ 16.6% *	+17.8% *
Deep skin hydration at 0.5 mm of depth	+15.2% *	+15.6% *	+16.1% *
Deep skin hydration at 1.5 mm of depth	+3.2%	+7%	+4.3%

Note: *Holm-Sidak Adjusted Wilcoxon signed-rank test p<0.05 vs T0.

Table 7 Investigator’s and Subjects’ Satisfaction Degree

COGA	Subjects %
	T7	T30	T90
No change	5%	5%	10%
Minimum improvement	20%	20%	20%
Moderate improvement	35%	30%	30%
Good improvement	40%	40%	35%
Excellent improvement	0%	5%	5%
PtGA	Subjects %
	T7	T30	T90
Much worse than expected	0%	0%	0%
Worse than expected	20%	35%	45%
As expected	40%	30%	10%
Better than expected	35%	25%	35%
Much better than expected	5%	10%	10%

Notes: Clinical Observer Global Assessment (COGA) on the wrinkles (nasolabial folds and marionette lines) and the skin laxity will be evaluated bilaterally at each study time by the investigator, using a five-degree scale (1 = no change, 2 = minimum improvement, 3 = moderate improvement, 4 = good improvement, 5 = excellent improvement). Patient Global Assessment (PtGA) will be evaluated after each post-baseline visit on aesthetic outcome, using 5-points Likert like scale (1 = much worse than expected, 2 = worse than expected, 3 = as expected, 4 = better than expected, 5 = much better than expected).