Introducing aesthetic regenerative scaffolds: An immunological perspective

Background

Skin aging arises from immunological responses to tissue deterioration and damage. Tissue repair processes encompass the regeneration of original tissue and ‘scarless’ wound healing seen in foetuses, and the extreme fibrotic responses and scarring seen in adults. Anti-aging aesthetic medicine uses interventions like biomaterial-based fillers to influence these immunological responses and renew aged tissue structure and function. At filler injection sites, an inflammatory response occurs that causes a spectrum of outcomes, ranging from tissue regeneration to fibrosis and filler encapsulation. Importantly, the resulting inflammatory pathway can be predetermined by the biomaterial injected.

Aims

By understanding this immunological process, we can develop Aesthetic Regenerative Scaffolds (ARS) - aesthetic injectable biomaterials - to direct inflammatory wound healing away from chronic, fibrotic responses, and towards physiological tissue regeneration.

Materials and Methods

We identified and reviewed literature on the immunological and cellular responses to injected dermal fillers, whereby the wound healing response to the injection was moderated under the influence of an injected biomaterial.

Results

We described the mechanisms of dermal wound healing and the use of ARS to direct healing towards tissue regeneration instead of scarring. We also summarised studies on extracellular matrix remodeling by calcium hydroxylapatite. We found that Calcium hydroxylapatite fillers produce collagen as they gradually degrade and their spherical structures serve as a scaffold for tissue regeneration. Furthermore, CaHA improved fibroblast contractility, collagen type III and elastin production, proliferation and angiogenesis with less inflammation than hyaluronic acid fillers.

Discussion

Regneration pathways can be influenced at specific points between a facial filler biomaterial and the wound healingmechanisms at its site of implantaion.

Conclusion

Physicians can select scaffolds that direct the immune response away from a fibrotic chronic inflammatory pathway and towards regeneration to enable true repair of the aging skin.     

Neocollagenesis in human tissue injected with a polycaprolactone-based dermal filler

A novel dermal filler containing polycaprolactone (PCL) has been introduced into the aesthetic market. A recently published study has shown that the PCL-based dermal filler induces neocollagenesis, a process associated with improvement in appearance of the skin, in rabbit tissue. In this pilot study, we investigated whether the PCL-based dermal filler induces neocollagenesis in human tissue by histological analysis. Two patients who were enrolled in the study, and were willing to undergo temple lifting surgery, were injected intra-dermally with the PCL-based dermal filler. Thirteen months post-injection, biopsies were obtained for subsequent histological analysis. Histological analysis of tissue obtained from the biopsies (13 months post-injection) revealed that the PCL-based dermal filler shows collagen formation around the PCL particles and, therefore, supports similar findings previously shown in rabbit tissue. In conclusion, PCL particles are maintained in their original state 13 months post-injection.     

Aesthetic dermatology: What's new,what's true?

Aesthetic dermatology (AD) is a rapidly growing subspecialty of dermatology. The acceptance of AD in scientific community and the society is associated with its competence, efficiency, and seriousness. This review highlights some recent developments toward new tools, techniques, and understanding in the field of AD. Analyzing the specific needs of patients and assessing the effect by objective measurements is important for further progress. For long time ignored, white adipose tissue has gained increasing interest in biology and rejuvenation. Characterization of dermal and subcutaneous white adipose tissue has made progress. The interaction of hyaluronic acid and calcium hydroxyl apatite (CaHA) fillers with adipocytes could be responsible for clinical efficacy. New developments of oral collagen treatment and highly diluted CaHA to contour the body outside the face will be discussed. Submental contouring using purified desoxycholic acid is another new development.     

Smads regulate collagen gel contraction by human dermal fibroblasts

BACKGROUND: Transforming growth factor (TGF)-beta induces fibroblast contraction that is implicated in efficient wound healing. The Smad family of proteins mediates signal transduction of the TGF-beta superfamily. However, its role in fibroblast contraction remains unclear. OBJECTIVES: To determine whether Smad proteins regulate fibroblast contraction. METHODS: We used an in vitro type I collagen gel contraction assay with human dermal fibroblasts infected with adenoviruses carrying Smads. RESULTS: Overexpression of Smad3, a major signal transducer in the Smad family, enhanced collagen gel contraction by fibroblasts when compared with fibroblasts overexpressing a control lacZ. Addition of a very low concentration of TGF-beta1 that did not affect the collagen gel contraction by itself enhanced the contraction by fibroblasts overexpressing Smad3. In contrast, TGF-beta1-mediated collagen gel contraction was suppressed by overexpression of Smad7, a major inhibitory regulator in the Smad family, in fibroblasts. In addition, inhibitors of the Erk and p38 pathways, PD98059 and SB203580, did not affect TGF-beta1-mediated collagen gel contraction by dermal fibroblasts. CONCLUSIONS: Modulation of Smad3 or Smad7 expression in dermal fibroblasts affected their contraction of collagen gels possibly by regulating TGF-beta signalling in fibroblasts.     

Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation

Background

Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose–response, safety, efficacy, and the ability to combine exosome treatment as a “skin primer”—for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA.

Methods

Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a “homing inflammatory environment” for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide—generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment.

Results

Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen.

Conclusions

Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome “priming of the skin” yielded enhanced skin quality faster than exosomes or CaHA alone.     

Calcium hydroxylapatite microspheres activate fibroblasts through direct contact to stimulate neocollagenesis

Background

Calcium hydroxylapatite (CaHA; Radiesse, Merz North America) restores volume and stimulates collagen production. The aim of this research was to explore the role of dilution and diffusion in microsphere distribution and the effect of CaHA concentration on activation of fibroblasts to produce collagen.

Methods

Ex vivo: Tissue dispersion of CaHA was assessed in abdominal tissue segments obtained from patients which were subsequently injected with CaHA diluted to 1:1 and hyperdiluted to 1:2. In vitro: Collagen type III (COLIII) and type I (COLI) expression of fibroblasts was evaluated after 24 and 72 h of incubation with CaHA concentrations of 1.5 (high dilution), 3.0, and 4.5 mg/ml (low dilution).

Results

Ex vivo: The 1:2 CaHA hyperdilution increased dispersion and decreased concentration of CaHA microspheres compared with the 1:1 dilution. In vitro: CaHA incubation resulted in an increased mean COLIII expression of 123% at 24 h. COLI synthesis did not change after 24 h but increased up to 124% at 72 h. Only fibroblasts in direct contact with CaHA increased COLIII expression. COLIII high-expressing cells were fully activated by CaHA and resulted in the same level of COLIII expression per cell independent of the CaHA dilution.

Conclusions

A 1:2 hyperdilution of CaHA increased tissue dispersion of CaHA microspheres. Direct contact of CaHA with fibroblasts was a key factor for inducing neocollagenesis. COLIII high-expressing cells were fully activated by CaHA and resulted in the same expression level of COLIII per cell independent of the CaHA amount in each dilution. This indicates that increased collagen expression was due to the activation of more fibroblasts.     

Adverse reactions to dermal fillers: a review of European experiences.

BACKGROUND: In Europe, numerous dermal fillers have been utilized for the past decade. A lot of drawbacks have been reported and sometimes, severe complications occurred. OBJECTIVE: Our purpose is to report the clinical aspects of the adverse reactions following injections of some of the dermal fillers. Histological aspects of complications are also described. RESULTS: Adverse reactions secondary to biodegradable products are usually time limited, but with the non-biodegradable products, we have observed severe, persistent, and recurrent complications. Histological examinations, in cases of non-biodegradable products, may show the presence and persistence of the filler. CONCLUSION: For the moment, there is no ideal dermal filler. All fillers can lead to adverse events and we need to inform patients fully before injecting. Clinical studies with long-term follow-up before launching a new product on the market are recommended. We believe that in Europe, at present, the CE mark is not a guarantee of safety of dermal fillers.     

Increased risk of late‐onset,immune‐mediated,adverse reactions related to dermal fillers in patients bearing HLA‐B*08 and DRB1*03 haplotypes

Even though manufacturers claim that the dermal fillers are nontoxic and nonimmunogenic, adverse events may occur. Clinically and histologically, most of the late onset adverse events present as an inflammatory response. To assess whether HLA polymorphisms are associated with late‐onset inflammatory adverse events related to dermal fillers. A total of 211 patients were included, of whom 129 experienced late‐onset inflammatory adverse events to different fillers (Inflammation group) and 82 who did not (Reference group). Patients completed a standardized questionnaire and provided a blood sample or oral swap for HLA testing. The study population consisted of 188 (89%) women and 23 (11%) men. The two study groups were similar in the distributions of filler type, location of injecting, allergy, autoimmune disease, gender, age, ethnicity, and smoking status. Of the 211 patients in the sample, 25 had the combination of HLA subtype‐B*08 and HLA subtype‐DRB1*03. This was 16.3% of the inflammatory group and 4.9% of the reference group. This combination of HLA subtypes was associated with an almost 4‐fold increase in the odds of developing immune mediated adverse events (odds ratio = 3.79, 95% CI 1.25‐11.48). Genetic polymorphisms such as HLA combinations may identify patients at risk of developing late onset immune mediated adverse events to dermal fillers.     

Adipose-derived stem cells as a new therapeutic modality for ageing skin

Stem cells are undifferentiated cells, which have the important properties of self-renewal and differentiation. Adipose-derived stem cells (ADSC) have relative advantages in accessibility and abundance compared to other kinds of stem cells. Regeneration therapy using ADSC has received attention in the treatment of various dermatologic diseases. In previous studies, ADSC were shown to have antioxidant, whitening and wound-healing effects in the skin through secretion of growth factors and by activating fibroblasts. In this study, we investigated whether ADSC could be used as an anti-ageing therapy, especially by dermal collagen synthesis and angiogenesis. Subcutaneous injection of ADSC significantly increased collagen synthesis in hairless mice, and dermal thickness, collagen density and fibroblast number also increased. In addition, procollagen type I protein and mRNA expression increased, which accounts for the increased dermal collagen density. Angiogenesis, which was visualized by CD31 and NG2 immunofluorescence stains, also increased in ADSC-treated skin. Our results suggest that ADSC therapy may be useful in ageing skin. Its effects are mainly mediated by stimulating collagen synthesis in dermal fibroblasts and increasing angiogenesis.     

Adverse reactions to dermal fillers: A review of European experiences

Background. In Europe, numerous dermal fillers have been utilized for the past decade. A lot of drawbacks have been reported and sometimes, severe complications occurred.

Objective. Our purpose is to report the clinical aspects of the adverse reactions following injections of some of the dermal fillers. Histological aspects of complications are also described.

Results. Adverse reactions secondary to biodegradable products are usually time limited, but with the non‐biodegradable products, we have observed severe, persistent, and recurrent complications. Histological examinations, in cases of non‐biodegradable products, may show the presence and persistence of the filler.

Conclusion. For the moment, there is no ideal dermal filler. All fillers can lead to adverse events and we need to inform patients fully before injecting. Clinical studies with long‐term follow‐up before launching a new product on the market are recommended. We believe that in Europe, at present, the CE mark is not a guarantee of safety of dermal fillers.     

The role of ascorbic acid on collagen structure and levels of serum interleukin-6 and tumour necrosis factor-alpha in experimental lathyrism

Lathyrism is characterized by defective collagen synthesis due to inhibition of lysyl oxidase, an enzyme essential for interfibrillar cross-linking. The lathyritic agent beta-aminoproprionitrile (beta-APN) is considered an appropriate agent for studying connective tissue metabolism. We investigated the effects of ascorbic acid on collagen structure and serum cytokine levels in experimentally induced lathyrism. Forty Wistar rats weighing 200-300 g were used in the study: three test groups of 10 rats each (groups 2, 3 and 4) and 10 rats used as a control group (group 1). Experimental lathyrism was induced with daily subcutaneous injections of beta-APN in the test groups for 40 days. On the 40th day, skin biopsies were taken from the control group (group 1) and group 2, to evaluate the effect of beta-APN on dermal collagen. After the 40th day, 10 rats received ascorbic acid 100 mg/kg intraperitoneally daily for 15 days (group 3) and 10 rats (group 4) received no medication and served as a control for group 3. On the 55th day, skin biopsies were taken from groups 3 and 4. Serum concentrations of interleukin-6 and tumour necrosis factor-alpha were assessed in each group by enzyme-linked immunosorbent assay. Ultrastructural examination of the skin biopsies in group 1 revealed normal-appearing epidermal and dermal structures. Group 2 showed disorganization of the epidermis and collagen structure, and vacuolization of the endoplasmic reticulum in fibroblasts. In group 3, ultrastructural examination revealed significant improvement in the structure of dermal collagen after administration of ascorbic acid, whereas the changes in group 4 were unremarkable. Ascorbic acid administration significantly decreased the concentrations of serum cytokines in group 3 compared with group 2 (P < 0.001). Ascorbic acid administration significantly improved dermal collagen structure and serum cytokine levels in experimental lathyrism.     

Histological evaluation of dermal tissue remodeling with the 1444‐nm neodymium:yttrium–aluminum–garnet laser in in vivo model

Laser lipolysis has a skin tightening effect by heating the deep dermis, in addition to the removal of fat tissues. The 1444‐nm neodymium:yttrium–aluminum–garnet (Nd:YAG) laser has been expected to be more effective and safe for laser lipolysis, due to higher affinity to fat and water, than 1064‐nm and 1320‐nm wavelengths. The purpose of this study was to evaluate the skin tightening effect of the 1444‐nm Nd:YAG laser through in vivo guinea pig models. The 1444‐nm Nd:YAG laser was used to irradiate shaved dorsal skin of the guinea pigs and compared with controls (no power, only tunneling). Immediately, 1 week, 1 month and 3 months after laser administration, full‐thickness skins were harvested and to evaluate dermal thickness, collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, using hematoxylin–eosin, Masson‐trichrome, Verhoeff's stain and Alcian blue stain. Dermal thickness showed an increase with time in all groups. In collagen organization, fibroblast proliferation, and intensity of elastic fibers and mucopolysaccharides, the treatment groups were higher than those of the control group, overall. Our study showed that the 1444‐nm Nd:YAG laser appeared to be effective for the skin tightening effect in in vivo guinea pig models. The 1444‐nm Nd:YAG laser can be used for skin tightening, as well as reduction of fat tissues.     

Anti-ageing effects of a new synthetic sphingolipid (K6EAA-L12) on aged murine skin

Recently, we reported on the anti-ageing effects of K6PC-5. This compound induced keratinocyte differentiation and fibroblast proliferation by increasing sphingosine-1 phosphate synthesis. We performed this study to confirm the anti-ageing effects of new synthetic products (the K6EAA series) derived from K6PC-5 through an amino group induction. Cellular responses such as differentiation, proliferation and calcium mobilization were investigated using cultured human keratinocytes and fibroblasts. Also, we measured the expressions of collagen mRNA and protein using real time RT-PCR and ELISA, respectively. The K6EAA-L12 product, selected by in vitro screening, was evaluated for anti-ageing effects on intrinsically and extrinsically (photo) aged models of hairless mice. In the intrinsically aged murine skin, K6EAA-L12 showed anti-ageing effects by activating collagen synthesis, eventually causing dermal thickening. Also, in the photo-aged skin, the dermal collagen density and dermal thickness were increased. In photo-aged murine skin, K6EAA-L12 increased stratum corneum integrity by increasing corneodesmosome density and improved the barrier recovery rate. However, there were no changes in the expressions of epidermal differentiation maker proteins. In conclusion, topical K6EAA-L12, a new synthetic K6PC-5 derivative, improves intrinsically and extrinsically (photo) aged skin by increasing the collagen density and improving the skin barrier function.     

SB-431542 inhibits TGF-beta-induced contraction of collagen gel by normal and keloid fibroblasts

BACKGROUND: Transforming growth factor (TGF)-beta induces fibroblast contraction, which is implicated in wound healing and keloid formation. SB-431542 is a novel specific inhibitor of TGF-beta type I receptor kinase activity. OBJECTIVE: We sought to determine whether SB-431542 inhibited TGF-beta-induced fibroblast contraction. METHODS: We used an in vitro type I collagen gel contraction assay with normal or keloid dermal fibroblasts incorporated. RESULTS: TGF-beta induced contraction of collagen gels with normal dermal fibroblasts incorporated, which was efficiently suppressed by SB-431542. Keloid fibroblasts showed higher basal contraction of collagen gels in the absence of TGF-beta than normal fibroblasts, which was enhanced by addition of TGF-beta. SB-431542 suppressed both the basal and TGF-beta-enhanced contraction of collagen gels by keloid fibroblasts. These inhibitory effects of SB-431542 were associated with suppression of TGF-beta-induced alpha-smooth muscle actin (alpha-SMA) expression and phosphorylation of Smad2 in normal and keloid fibroblasts. CONCLUSION: SB-431542 can suppress TGF-beta-induced contraction of collagen gel by normal and keloid dermal fibroblasts. Importantly, SB-431542 can inhibit basal contraction of collagen gel by keloid fibroblasts. These results suggest that an inhibitor of TGF-beta type I receptor kinase activity may have therapeutic potential for excessive skin contraction as observed in keloid.     

European evaluation of a new hyaluronic acid filler incorporating lidocaine

Background A new dermal filler has been developed with preincorporated lidocaine for the treatment of moderate/severe wrinkles. Aims Injector and patient evaluation of comfort and aesthetic results obtained with a new hyaluronic acid filler incorporating lidocaine (HAL) following treatment of nasolabial folds. Patients/Methods Three thousand five hundred and sixty‐six patients were recruited by 485 injectors across 16 countries. All patients had previously received facial fillers but now required further treatment. All patients received the new hyaluronic acid filler incorporating lidocaine. Results Injector assessment of HAL was that it was very easy to inject in > 75% of patients, and postinjection sculpting/massaging was very easy in most patients (> 70%). Both injectors and patients reported low patient pain levels, with patients experiencing less pain during all stages of the HAL injection procedure compared to previous dermal fillers. Over 95% of injectors rated the aesthetic effect of HAL as “excellent” or “good,” with 99.1% stating they would recommend treatment to a colleague and 99.4% recommending treatment to other patients. More than 90% of patients were happy with the treatment, and 99% would recommend HAL to friends. Conclusions The new hyaluronic acid filler incorporating lidocaine provides a more comfortable injection experience and improved aesthetic result for most patients compared with other dermal fillers used previously.     

Dermatofiller

The demand for minimally invasive cosmetic procedures is increasing rapidly every year. In addition to botulinum toxin and laser treatments, the injection of dermal fillers is one of the most relevant methods. Dermal fillers can be used for a multitude of indications: wrinkles (fine to deep), lip augmentation, facial deformities, sunken scars, and HIV-related lipoatrophy in hands, neck and décolleté. There are currently 160 dermal fillers on the market. They differ greatly in terms of origin (own or cadaveric-derived, animal, bacterial fermentation or synthesis), duration of the effect and breakdown properties (temporary, semi-permanent, permanent), injection depth (dermal, subcutaneous, supraperiosteal), and risk profile. Physicians who administer dermal fillers should have a thorough knowledge of their characteristics and of the anatomy of the area to be treated. This is essential for correct administration and optimal aesthetic results. Prior to any treatment, details of the procedure, the desired effects, durability, and potential risks of the filler to be injected should be discussed with the patient. The choice of dermal filler, the injection technique, and the volume to be administered are determined according to the anatomic site, the type of defect, the desired effect, and physician experience.     

In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin

OBJECTIVE: To determine whether endogenous synthesis of new extracellular matrix may contribute to the degree and duration of clinical benefits derived from cross-linked hyaluronic acid dermal filler injections. DESIGN: In vivo biochemical analyses after filler injections. SETTING: Academic referral center. PARTICIPANTS: Eleven healthy volunteers (mean age, 74 years) with photodamaged forearm skin. Interventions Filler and vehicle (isotonic sodium chloride) injected into forearm skin and skin biopsy specimens taken 4 and 13 weeks later. MAIN OUTCOME MEASURES: De novo synthesis of collagen, the major structural protein of dermal extracellular matrix, was assessed using immunohistochemical analysis, quantitative polymerase chain reaction, and electron microscopy. RESULTS: Compared with controls, immunostaining in skin receiving cross-linked hyaluronic acid injections revealed increased collagen deposition around the filler. Staining for prolyl-4-hydroxylase and the C-terminal and N-terminal epitopes of type I procollagen was enhanced at 4 and 13 weeks after treatment (P<.05). Gene expression for types I and III procollagen as well as several profibrotic growth factors was also up-regulated at 4 and 13 weeks compared with controls (P<.05). Fibroblasts in filler-injected skin demonstrated a mechanically stretched appearance and a biosynthetic phenotype. In vitro, fibroblasts did not bind the filler, suggesting that cross-linked hyaluronic acid is not directly stimulatory. CONCLUSIONS: Injection of cross-linked hyaluronic acid stimulates collagen synthesis, partially restoring dermal matrix components that are lost in photodamaged skin. We hypothesize that this stimulatory effect may be induced by mechanical stretching of the dermis, which in turn leads to stretching and activation of dermal fibroblasts. These findings imply that cross-linked hyaluronic acid may be useful for stimulating collagen production therapeutically, particularly in the setting of atrophic skin conditions.     

Extensive necrosis after injection of hyaluronic acid filler: case report and review of the literature

Background Use of dermal fillers for soft tissue augmentation has become an integral part of aesthetic practices. Dermal fillers temporarily remove the appearance of rhytids and reduce the depth of skin folds. Even with the most experienced of injectors, adverse effects can and do occur ranging from mild bruising to severe injection necrosis. Aims Physicians should be able to treat the severe complication of vascular necrosis and detect impending necrosis after injection of a dermal filler, especially with hyaluronic acid fillers. Materials and Methods Case report of a patient who was followed for 6 months from time of injection of hyaluronic acid filler to complete healing of wound. Results Complete wound healing was achieved with early recognition and institution of treatment. Discussion We review a case report of injection necrosis and methods used to prevent and treat this complication. Conclusion Early recognition of vascular necrosis with specific protocol for treatment after injection necrosis with hyaluronic acid fillers improves the outcome of wound healing.     

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.