Comparison of polycaprolactone and calcium hydroxylapatite dermal fillers in a rat model

Polycaprolactone (PCL) and calcium hydroxylapatite (CaHA) are semipermanent dermal fillers that are frequently preferred in the last decade. This study aims to compare the effects of these two fillers in the rat skin. A total of 30 female rats were divided into; control, PCL, and CaHA group. Tissue samples taken at the second and fourth month were stained with hematoxylin‐eosin, Masson trichrome, collagen type 1, and 3 immunohistochemical antibodies. Collagen density was quantitatively compared using the Image J computer program. At 2 and 4 months, the density of collagen increased in both filler groups compared to the control group. There was no significant difference between collagen density or type 1 and type 3 collagen H scores in the filler groups. The number of fibroblast nuclei was significantly higher in the PCL group at 4 months compared to the other two groups. Dermis thickness was found to be superior in both filler groups compared to the control group at the fourth month, there was no significant difference between the filler groups. We compared the effect of CaHA and PCL filler on collagenization histologically and immunohistochemically. We found that PCL and CaHA fillers are effective in increasing dermal collagen density, type 1 and type 3 collagen amount, and preventing dermis atrophy and showed that they have no advantage over each other in this respect. We have shown that PCL filler provides more fibroblast increase compared to CaHA filler and the effect of stimulating fibroblast proliferation takes longer.     

Polycaprolactone facial volume restoration of a 46‐year‐old Asian women: A case report

A 46‐year‐old Asian women was treated with a next‐generation bioresorbable biostimulatory polycaprolactone (PCL)‐based dermal filler to restore facial volume loss. Before‐ and after (12 weeks of follow‐up)‐treatment photographs were analyzed and compared. In addition, before‐ and after‐treatment contour images were recorded using the Vectra^®XT 3D imaging system (Canfield Scientific, Inc.). Improvement of facial volume in multiple tissue layers was observed at 4 and 12 weeks of follow‐up. Total facial rejuvenation to correct descending soft tissue with a PCL‐based dermal filler was achieved through volume restoration in multiple tissue layers of the face.     

Tumescent anesthesia for reducing pain,swelling, and ecchymosis during polycaprolactone filler injections in the face

PCL filler can be injected in two major ways to control pain. One such method involves mixing 0.3cc of PCL filler with lidocaine, and the other is the method introduced in this report, which involves pre-injection with a tumescent solution. It is hard to reduce pain effectively with pre-mixing PCL filler with lidocaine because there may be not enough time to act lidocaine solution effect immediately for pain control. The pre-mixing method changes the properties of the original filler, especially the property of the CMC portion. Therefore, in my simple and novel technique, tumescent solution is injected, followed by PCL filler which preserves the original CMC property. This is done after sedation of the tissue by the tumescent solution and dissection of soft tissue to create a space for the ensuing PCL injection. After pre-injection with tumescent solution, histological analysis indicated that the tissue did not become irritated in response to the foreign body material (PCL filler) or the mechanical trauma caused by the needle. That is the key mechanism of the tumescent injection method for reducing tissue reaction and that may reduce pain and swelling during and after PCL filler injections.     

Granuloma as a complication of polycaprolactone-based dermal filler injection: ultrasound and histopathology studies

In aesthetic medicine, there has been an ongoing search for an ideal dermal filler to offer zero complication rate. Polycaprolactone-based dermal filler (PCL) has been available since 2009.

The purpose of the paper was to present a case of granuloma as a complication of PCL injection, which has not been reported so far by other researchers. A 68-year-old female was injected with PCL. One year later, nodules accompanied by bluish skin discoloration developed within the injection site. Ultrasound and histopathology studies were performed. The examinations confirmed the presence of foreign body granuloma after PCL, which makes it the first reported case worldwide. The published data analyses showed general lack of studies and case reports to address this issue. The PCL, like an injection of any soft tissue filler, may lead to serious complications, such as granuloma formation. This makes further research legitimate and necessary.     

Hand recontouring with calcium hydroxylapatite (Radiesse)®

The aging hand is a common area of concern for many patients. Until recently, adequate treatment options have been hampered by pain of injecting into the dorsum and, post-injection, by the absence of longevity of treatment. In this article, we describe the off-label use of the soft tissue filler calcium hydroxylapatite (CaHA; Radiesse) for hand rejuvenation. The product is inherently biocompatible and, when placed in soft tissue, induces neocollagenesis.
An alternative injection mixture of CaHA combined with lidocaine is described, as well as the novel "bolus" injection technique. The CaHA-lidocaine emulsion reduces the pain of injection to nearly none at all, improves the rheology of the procedure, and allows for deposition of the product into the correct plane of tissue. The volume of CaHA injected as well as the amount of lidocaine used for the mixture vary according to physician preference. In our practice, 1.3 mL of CaHA combined with 0.5 mL lidocaine per hand usually appears to be sufficient to improve the appearance of the atrophic dorsum of the hand.
Side-effects of CaHA (Radiesse), particularly in this off-label application, are minimal and of short duration. The aesthetic result is immediate and generally persists for longer than 6 months. As a treatment option, hand rejuvenation with CaHA (Radiesse) is a very gratifying procedure both to the patient and to the physician.     

Comparative clinical study for the efficacy and safety of two different hyaluronic acid-based fillers with Tri-Hyal versus Vycross technology: A long-term prospective randomized clinical trial

Background

Hyaluronic acid-based fillers have an immediate volumizing effect for the treatment of dermal contour deformities and to smooth dermal depressions formed by the loss of volume. A previous study on 2016–2018 has shown the efficacy and safety of the HA-based filler ART FILLER® Volume on the midface only, but not in a comparative manner.

Methods

In this context, an 18 months prospective randomized single-blind study of the non-inferiority of ART FILLER® Volume versus the reference product Juvéderm Voluma® was performed on the midface, temple, and jawline, and non-comparative study on the chin. The efficacy and the longevity were evaluated for the selected face areas via dedicated clinical scoring systems after a single filler injection without any re-touch or re-injection. The short- and long-term adverse effects were also recorded.

Results

The observations confirmed the non-inferiority of ART FILLER® Volume versus the reference product on the different injected areas. For both fillers, the beneficial effects on volumes restoration were maintained 18 months post-injection; however, these effects were diminished among the time. Furthermore, injections of Art Filler® Volume were well tolerated by the subjects and showed less acute side effects compared with the reference product that may be explained by a lower induction of inflammation.     

The effect of combined hyaluronic acid filler injection and radiofrequency treatment: A clinic histological analysis

Background

Hyaluronic acid (HA) filler injections have increased in popularity. They are usually performed in combination with other treatment modalities, including lasers and energy-based devices, to enhance cosmetic results. Theoretically, HA and other filler injections should be performed after laser- or energy-based device treatments. In some instances, however, practitioners are asked to administer laser- or energy-based device treatment after HA dermal filler injection. There is a concerning possibility of HA filler degradation as a result of bulk heating generated by lasers or energy-based devices, especially radiofrequency (RF).

Aim

To evaluate the effect of RF treatment at different time points on HA degradation in vivo, using clinicohistological analysis.

Patients/methods

Fourteen volunteers were recruited and received intradermal HA filler injections in four sites on the abdomen. One site served as the control, and the other three sites were treated with monopolar RF on the same day after injection, at 14 and 28 days post-injection. Skin biopsies were performed at baseline and 56 days after HA injection. Histopathological sections were reviewed for residual filler in the tissue.

Results

The results showed that HA grading scores decreased in five (35.71%), one (7.14%), and one (7.14%) participants when RF was performed immediately, 14 and 28 days after injection, respectively.

Conclusion

In conclusion, RF treatment after HA filler injection may affect the integrity of the HA filler in the tissue, especially if RF treatment was performed on the same day after HA injection.     

Histological spectrum of cutaneous reactions to aspirin in chronic idiopathic urticaria

BACKGROUND: During a clinical trial, we obtained 16 biopsies of skin eruptions induced by aspirin in patients with chronic idiopathic urticaria (CIU). In this setting, aspirin triggers skin eruptions through a well-established non-immunological mechanism involving the inhibition of cyclooxygenase type I. This presented the rare opportunity to evaluate histological features of a series of skin eruptions induced by a drug acting through a defined mechanism in a controlled experimental setting. OBJECTIVE: Histological analysis of 16 biopsies of skin eruptions induced by oral aspirin challenge in patients with CIU. DESIGN: Microscopic analysis of tissue sections. PATIENTS: 16 patients with CIU. RESULTS: Aspirin (up to 500 mg) induced a restricted range of histological responses with a classic pattern of urticarial tissue reaction occurring in the majority of (12 of 16) cases. Two biopsies showed an interstitial fibrohistiocytic (granuloma annulare-like) reaction pattern. One case showed only a sparse perivascular lymphocytic infiltrate, and paucicellular dermal mucinosis was observed in one case. CONCLUSIONS: Polymorphism of histological patterns induced by aspirin suggests that in addition to the drug-specific mechanisms triggering drug eruptions, individual factors also play a role in determining the ultimate histological phenotype of a drug response.     

Improved method for rhesus monkey or rat skin preparation and cryosectioning for topical or transdermal skin distribution studies

Abstract A method for preparing skin biopsies for cryosectioning was developed to accurately obtain samples from specific areas of the dermis, while minimizing contamination with epidermal tissue. Routine preparation of 6 mm punch biopsies from freshly excised, full-thickness skin produced contraction and folding of the edges of the biopsy prior to mounting for snap-freezing and cryosectioning. Sample orientation was ruined, and cryosections were heterogeneous with respect to dermal structures and/or to dermal and epidermal layers. Biopsy artifacts were prevented by prefreezing skin over dry ice prior to taking biopsies. The biopsies were held frozen on dry ice until they were mounted on cryostat pegs with flattened, frozen OCT surfaces; then they were snap-frozen in chilled OCT in an isopentane bath cooled with liquid nitrogen. The method for determining skin level homogeneity of cryosections consisted of taking 10 μm cryosections for histology between sections sampled for drug level analysis. The histological sections were fixed in 5% acetic acid in methanol and stained with hematoxylin and eosin to define the skin layers and structures associated with each sample for analysis. Histological sections from prefrozen skin had fewer processing artifacts, and dermal cryosections free of epidermal contamination were dramatically increased compared to the routine procedure.     

Association between collagen production and mechanical stretching in dermal extracellular matrix: In vivo effect of cross-linked hyaluronic acid filler. A randomised,placebo-controlled study

BackgroundThe effects of hyaluronic acid (HA) injection on tissue collagen anabolism are suggested to be related to the induction of mechanical stress, causing biochemical changes in skin physiology.ObjectivesTo ascertain the association between dermal mechanics modulated by a hyaluronic acid-based filler effect and metabolism.MethodsSixty females were randomised to receive a 0.5 mL injection of HA gel or isotonic sodium chloride (control) in the arm. Skin biopsies were taken at baseline and after 1, 3 and 6 months. Protein and gene expression of procollagen, matrix metalloproteinases (MMP) and MMP tissue inhibitors (TIMP1) were measured blind by ELISA and qPCR, respectively. Injected volumes were measured by high-frequency ultrasound and radiofrequency analysis. Skin layer effects of injections were analysed by finite element digital modelling.ResultsOne month after injection, the filler induced an increase in procollagen (p = 0.0016) and TIMP-1 (p = 0.0485) levels and relative gene expression of procollagen III and I isoforms compared with the controls. After 3 months, procollagen levels remained greater than in the controls (p = 0.0005), whereas procollagen expression and TIMP-1 and MMP content were no longer different. Forty-three percent of the injected filler volume was found at 1 month, 26% after 3 months and 20% after 6 months.LimitationsThe ultrasound imaging technique limited the scope of the investigation and precluded an evaluation of the action of the filler at the hypodermic level.ConclusionsIntegrating both mechanical and biological aspects, our results suggest that mechanical stress generated by cross-linked HA plays a role in dermal cell biochemical response.     

Clinical, histologic and electron microscopic findings after injection of a calcium hydroxylapatite filler.

BACKGROUND: Calcium hydroxylapatite (CaHa) is one of many newly available soft tissue fillers. OBJECTIVE: We have, in this pilot study, evaluated the clinical, histologic and electron microscopic ultrastructural changes seen with CaHa at 1 and 6 months after skin injection. METHODS: Each of the three subjects was injected in the postauricular area with 0.1 cc of CaHa gel. A 3-mm punch tissue biopsy was taken at 1 and 6 months post-injection. Biopsies were analyzed by histopathology and electron microscopy. Clinical results after injection of the nasolabial folds were also evaluated. RESULTS: CaHa particles were found to persist at 6 months with evidence of new collagen formation being seen. Patients still showed clinical improvement at this time. CONCLUSION: This study is the first in vivo ultrastructural analysis of the biologic response to CaHa in human skin. CaHa shows clinical, histologic and electron microscopic evidence of persistence at 6 months.     

Localized granulomatous reaction to a semi-permanent hyaluronic acid and acrylic hydrogel cosmetic filler

Dermalive, an injectable skin filler composed of a combination of synthetic hyaluronic acid and acrylic hydrogel particles was recently developed for soft tissue augmentation. Dermalive produces longer term results than temporary injectable fillers and is associated with a reportedly low incidence of adverse reactions. We describe a marked local reaction to the injection of Dermalive in the nasolabial fold developing within 4 months with histological confirmation of a granulomatous response. To our knowledge there has been only one previous report of a local granulomatous reaction to Dermalive.     

A prospective multicenter clinical trial evaluating the efficacy and safety of a hyaluronic acid-based filler with Tri-Hyal technology in the treatment of lips and the perioral area

Background

Age-related changes of facial soft tissue cause clinical signs of facial aging such as lip atrophy, marionette lines, and an accentuated nasolabial fold. These changes can be modified using dermal fillers.

Aims

To evaluate efficacy, longevity, and safety of a cross-linked hyaluronic acid-based filler with Tri-Hyal technology in the treatment of lips, nasolabial folds, and marionette lines.

Materials and Methods

This prospective, multi-center trial evaluated injections of three different areas (lips, nasolabial fold alone, or with marionette wrinkles) with a soft tissue filler containing 25 mg/ml cross-linked hyaluronic acid and 0.3% lidocaine. Primary endpoint was the aesthetic correction 3 weeks after one injection session without touch-up. Follow-up was 18 months. Assessments were performed using the Global Aesthetic Score (GAS), clinical scoring based on photographic scales, high-frequency ultrasound imaging, and the Global Aesthetic Improvement Scale (GAIS).

Results

In total, 100 subjects were injected. GAS improved significantly for all treatment indications at 3 weeks (p < 0.0001). Success rates were highest for nasolabial folds (98.4%), followed by marionette lines (94.4%) and lips (73.5%). After 18 months post-injection, success was observed in 91%, 88%, and 33% of subjects injected into nasolabial folds, marionette lines, and lips, respectively. GAIS scored highest for nasolabial folds (SGAIS: 71%; IGAIS: 40%), followed by marionette lines (SGAIS: 56%; IGAIS: 33%) and lips (SGAIS: 30%; IGAIS: 22%) at 18 months follow-up.

Conclusions

The filler demonstrated high efficacy and safety in all indications. Regional differences in longevity were evident. Thus, the necessity of regional retreatments should be discussed with patients before injection.     

Generalized livedo reticularis induced by silicone implants for soft tissue augmentation

Silicone is one of the most widely used filler for facial cosmetic correction and soft tissue augmentation. Although initially it was considered to be a biologically inert material, many local and generalized adverse effects have been reported after silicone usage for cosmetic purposes. We present a previously healthy woman who developed progressive and persistent generalized livedo reticularis after cosmetic surgery for volume augmentation of buttocks. Histopathologic study demonstrated dermal presence of interstitial vacuoles and cystic spaces of different sizes between the collagen bundles, which corresponded to the silicone particles implanted years ago. These vacuoles were clustered around vascular spaces and surrounded by a few foamy macrophages. General examination and laboratory investigations failed to show any evidence of connective tissue disease or other systemic disorder. Therefore, we believe that the silicone implanted may have induced some kind of blood dermal perturbation resulting in the characteristic violet reticular discoloration of livedo reticularis.     

Quantitative analysis of epithelial papillae in patients with oral lichen planus

Background  The oral mucosa is relatively vulnerable to pathological processes, and is often affected by autoimmune and malignant diseases. The oral epithelium is normally non-homogeneous, and joins to the connective tissue through interlocking of its downward projections in the form of papillae.
Objective  This study aims to conduct a histomorphometric study of the epithelial papillae in patients with oral lichen planus (OLP).
Material and method  This study was based on 100 cheek mucosa biopsies from patients with OLP (66 white reticular and 34 atrophic-erosive) (13 males and 87 females, with a mean age of 54.95 ± 13.64 years). A histological and morphometric evaluation was made, based on imaging analysis with MIP software 4.5 for studying the papillary structure in the patients with OLP.
Results  The mean epithelial thickness was 227.5 ± 78.5 µm. The different papillary measures – BLS (distance from basal layer to epithelial surface), DPS (distance from dermal papilla top to epithelial surface), DPW (dermal papilla width), and DPD (interdermal papilla distance between two papillae) – yielded no statistically significant differences with respect to age, sex, smoking and clinical form. However, a significant correlation was observed in relation to papilla width and inflammatory infiltrate ( P  = 0.031).
Conclusions  The application of this imaging system is useful for measuring variations in epithelial papillary architecture.

Conflicts of interest

None declared.     

No association found between late-onset inflammatory adverse events after soft tissue filler injections and the adaptive immune system

Background

To date, it is unknown why some individuals develop late-onset inflammatory adverse events after treatment with fillers. These events may result from various factors, including an immunological response of the adaptive immune system.

Objective

In a pilot study, we looked for evidence that is there a relation between late-onset inflammatory adverse events and the presence of immune cells surrounding the injected filler.

Methods and Materials

We included 47 patients, of whom 20 experienced late-onset inflammatory adverse events to different fillers (inflammatory group) and 27 who did not (reference group). A biopsy was taken from the area of the adverse event. Hematoxylin–eosin staining and immunohistochemistry analysis with CD3 (T-cells) and CD68 (macrophages) on paraffin tissue sections was used to assess the biopsies.

Results

Immune cells were found in biopsies obtained from 18 of 47 patients: Nine biopsies from the inflammation group and nine from the reference group. All these 18 cases showed CD68-positive immune cells. Virtually no CD3-positive immune cells were found.

Conclusion

Our results indicate that there is no T-cell activity in biopsies from areas with late-onset adverse events after filler injections. The macrophages found in the biopsies are probably not responsible for the inflammatory response.     

Reticular variant of mid-dermal elastolysis

A 49-year-old man presented with a 20-year history of an asymptomatic reticular eruption on his upper trunk. On examination, there were well-demarcated orange-red patches with reticular margins and irregular central atrophy on the lateral chest and proximal upper limbs. Skin biopsies showed histological evidence of elastophagocytosis with scant lymphocytic inflammation. Elastin stains demonstrated focal loss of elastic fibers in the reticular dermis, consistent with mid-dermal elastolysis. Mid-dermal elastolysis is a rare disorder characterized by focal loss of elastic tissue in the mid-dermis. The etiology remains obscure. Reticular presentations of mid-dermal elastolysis have rarely been described and extend the clinical spectrum of dermal elastolytic disorders.     

Sulfur revisited

Sulfur is a time-honored therapeutic agent useful in a variety of dermatologic disorders. Its keratolytic action is due to formation of hydrogen sulfide through a reaction that depends upon direct interaction between sulfur particles and keratinocytes. The smaller the particle size, the greater the degree of such interaction and the greater the therapeutic efficacy. When applied topically, sulfur induces various histologic changes, including hyperkeratosis, acanthosis, and dilatation of dermal vasculature. One study showed that sulfur was comedogenic when applied onto human and rabbit skin, findings that were not reproduced in other studies. About 1% of topically applied sulfur is systemically absorbed. Adverse effects from topically applied sulfur are uncommon and are mainly limited to the skin. In infants, however, fatal outcome after extensive application has been reported.     

Oral acitretin in psoriasis: drug and vitamin A concentrations in plasma, skin and adipose tissue.

The purpose of the present study was to determine the concentrations of acitretin and its main metabolite, 13-cis acitretin, in epidermis, subcutis and plasma in twelve psoriatic patients treated with 30 mg acitretin orally daily for 6 months. In addition, endogenous concentrations of vitamin A were monitored. Blood samples and biopsies from normal appearing skin were obtained prior to therapy, after 1 and 6 months of treatment and finally 1 month after cessation of therapy. Using a highly sensitive liquid chromatography method concentrations of synthetic retinoids and endogenous retinoid (retinol, 3,4-didehydroretinol) were analysed in hydrolyzed tissue samples and plasma. Steady-state concentration of acitretin in epidermis (17 +/- 9 ng/g) was reached within 1 month of therapy. There was a significant correlation between the individual plasma trough value and the epidermal concentration of acitretin after 1 month of therapy. The acitretin concentrations in subcutis varied from 15 to 1437 ng/g, but the mean values at 1 and 6 months of therapy were similar (177 and 227 ng/g, respectively). After stopping therapy the acitretin level was below the detection limit in both epidermis and serum within 1 month in 9 out of 12 patients. In contrast, only 3 of the patients were negative for acitretin in subcutis biopsies obtained 1 month after stopping therapy. The occurrence of a presumed tissue contaminator with characteristics similar to 13-cis acitretin prevented quantitation of this metabolite in many subcutis samples. The epidermal, subcutis and serum composition of retinol and 3,4-didehydroretinol remained unchanged during therapy, indicating no or only minimal interaction between acitretin and endogenous vitamin A metabolism.