Ravello ® doesn’t require retouching for every 6 months but lasts over 2 years after 3 times of initial treatment.
After Ravello ® treatment, patients can able to ordinary daily life.

Ravello ® is a non-surgical treatment and recovery time is shorter than fat graft due to formation of biodegradable scaffold and generation of collagensis, do not need to worry about engraftment of autologous fat.

Fig 1. The production of collagen fibres in the dermis.
The fibroblast secretes the procollagen fibre into the extracellular matrix, where they form larger collagen bundles. Elastin is also secreted and assembled into the collagen-based macromolecular structure. (By permission of MINERVA Research Labs Ltd – London)

Fig 2. Collagen content of skin is maximal between the 2nd and 3rd decade, after which there is a slow depletion and loss of collagen (and associated ECM components such as elastin and GAGs). The loss of collagen is clearly correlated with changes to appearance attributes which are typically referred to as fines lines and wrinkles. (By permission of MINERVA Research Labs Ltd – London)

Inject diluted Ravello ® into the subcutaneous layer of the skin.

Firstly wrinkle improvement can be shown with WFl (Water for injection) and diluted Ravello ®

Within some days, after absorbing water, only Ravello ® particles left

New cells are gathered around PLLA & HA and increasing fibroblasts.

Increased fibroblasts stimulate collagen regeneration and improve skin folds.

Regenerated collagen lasts for 2 years and Ravello ® particles are biodegraded.

Hematoxylin and eosin (H&E) staining can be used to observe the local inflammatory response and determine the biocompatibility of PLA microsphere. In Fig. 6A, the results showed that no obvious histopathological damage or inflammatory reaction was detected three days after the treatment of PLLA MS, indicating excellent biocompatibility.

As comparison, the inflammatory cells in the PDLA MS group were significantly more than those in the PDLLA MS and PLLA MS group, it proved that the inflammatory response in the skin injected by PDLA MS was stronger than that in PDLLA MS and PLLA MS group.

The expression level of IL-1β, IL-6 and TNF-α were evaluated by confocal laser scanning microscope (CLSM). As shown in Fig. 6B, on Day 3, the fluorescence signal of FITC in PDLA MS group was obviously strong, which showed the level of inflammatory response in tissues surrounding of the injected site with PDLA MS was significantly stronger than the level of inflammatory response which injected with PLLA MS or PDLLA MS.

The semi-quantitative histograms in Fig. 6C showed that the expression levels of IL-1β, IL-6 and TNF-α around the injected site induced by PDLA MS were 3.2, 2.5 and 2.0 times higher than those of inflammatory factors induced by PLLA MS, and 2.3, 1.9 and 1.4 times higher than those induced by PDLLA MS, respectively.

This finding was in consistence with the results in H&E staining, confirming that PLLA MS has good biocompatibility and thus is more suitable as dermal filler (Skin Booster or Collagen Stimulator).

[Reference] Chinese Chemical Letters 32 (2021) 577-582

(Fig. 6A) H&E staining of the skin at the injection site of PDLA MS, PLLA MS, and PDLLA MS.

(Fig. 6B) Immunofluorescence determination of skin inflammatory factors on Day 3 after microsphere injection. Green fluorescence showed FITC labeled inflammatory factors and blue fluorescence showed nuclei.

[Reference] Chinese Chemical Letters 32 (2021) 577-582

The content of type I collagen in the PLLA group was still 84.7%, and type III collagen was 15.1% on 30 day.

Total of type I and type III collagen in the PLLA group were 1.4 times than the collagen in the PDLA group, and 1.1 times than the collagen in the PDLLA group (Fig. 7C). Which showed that PLLA MS has the most obvious effect on stimulating collagen regeneration, and it is indeed suitable for usage as dermal filler in comparison with the other two chiralities.

Masson staining and picrosirius red staining revealed that PLLA MS conducted the strongest stimulation toward the regeneration of collagen fibers in the skin, which is an important factor as a filler.

Therefore, compared with PDLA MS and PDLLA MS, PLLA MS is a skin filling material with lower cost, lower side reaction, better filling effect and excellent collagen stimulating effect. Furthermore,
PLLA MS can contain collagen and other substances that are beneficial to skin repair and collagen regeneration, which can be released slowly through PLLA degradation to achieve better cosmetic effect.

In brief, PLLA MS is a valuable and superior dermal filler (Skin Booster or Collagen Stimulator).

(A) Masson

staincinogll a gen is stained blue, nuclei are stained dark brown, muscle tissue is stained red, and cytoplasm is stained pink

The skin picture at the injection site of three kinds of PLA microsphere on Day 30.

(B) Picrosirius red staining

Picrosirius red (PSR) staining is a commonly used histological technique to visualize collagen in paraffin-embedded tissue sections.
PSR stained collagen appears red in light microscopy.
However it is largely unknown that PSR stained collagen also shows a red fluorescence, whereas live cells have a distinct green autofluorescence

(C) Semi-quantitative analyses of type I and type Ill collagen fibers.

Data are presented as mean A: standard deviation
(n = 3, *P < 0.05, **p < 0.01, ***p < 0.001, ns: not significant)
Type l collagen fibers are red or yellow, type lll collagen fibers are green.

Ravello ® was almost similar to company G’product, a licensed product, as a result of the control test for decomposition.