A Composite Dermal Filler Comprising Cross-Linked Hyaluronic Acid and Human Collagen for Tissue Reconstructions

( Z Hun Kim ),( Yong Jun Lee ),( Sun Mi Kim ),( Ho Jin Kim ),( Chang Koo Yun ),( Yong Soo Choi ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.3

In this study, we developed a composite filler comprising cross-linked hyaluronic acid (HA) and human collagen (COL) derived from the human umbilical cord with the aim of improving its biocompatibility and longevity compared with commercially available fillers. After HA/ COL composite fillers were made in two different ratios (10:1 and 5:1), the physical properties of the fillers were evaluated. The interior morphologies and in vivo weight change of these hydrogels were also characterized at 1-16 weeks after injection into mice. To evaluate their biocompatibility and durability in vivo, we injected the composite fillers into nude mice subcutaneously. The variations of injected gel weight were measured and compared with the commercial dermal fillers (Restylane and TheraFill). The composites showed improved or similar physical properties (complex viscosity of 19-22 × 105 cP, and injection force of 10- 12 N) over the commercial dermal fillers. Sixteen weeks following the injection, the ratio of remaining composite filler weight to initial weight (75.5 ± 16.9%; 10:1) was shown to be greater than that of the commercial fillers (43.2 ± 8.1%, Restylane; 12.3 ± 5.3%, TheraFill). In addition, immunohistochemical analysis with angiogenesis-related markers such as isolectin and vWF revealed newly formed blood vessels and cellular influx into the composite filler, which were not observed in the other fillers. These results clearly suggest that the HA/COL composite filler is a superior candidate for soft tissue reconstruction. The filler we developed may be a suitable candidate as an injectable dermal filler for tissue augmentation in humans.

세포외기질(ECM) 생체소재 기반 필러 개발 연구

김나현,박상혁 대한의용생체공학회 2019 의공학회지 Vol.40 No.4

Numerous efforts are being made to develop an ideal dermal filler that should be bio-compatibility, nonimmunogenicity, long-lasting and biodegradable without a toxic secretion. Biomaterials of dermal fillers are hyaluronic acid filler, calcium filler, PMMA filler and collagen filler depending on the ingredient. Although hyaluronic acid (HA) is most widely used, it has shortages such as short shelf life and low mechanical strength compare to extracellular matrix (ECM). The cartilage ECM composed of collagen type II, proteoglycans, glycosaminoglycans (GAGs) and in a minor part with glycoproteins. In this study, we developed a cartilage ECM injectable filler capable of improving biocompatibility and longevity compared with hyaluronic acid (HA) fillers. The ECM hydrogel was cross-linked by the reaction of N- (3-Dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) for mechanical enhancement. Prepared ECM filler was compared with cross-linked HA by butanediol diglycidyle ether (BDDE), which is the most widely used natural polymers for dermal filler. In the results, the articular cartilage ECM hydrogel has great potential as a dermal filler to improve the biophysical and biological performance.

Polydioxanone(PDO) dermal filler and its collagen regenerating effect in skin layer

이청천,( Lia Priscilla ),곽민석,전효선,심용호,권한진 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1

As rapid growth of interest in beauty, market of cosmetic dermal filler is emerging in the world. Since the first cross-linked hyaluronic acid (HA) dermal filler was approved in FDA, it occupied major part of this market up to this day. However, the HA filler has a limit because of its toxicity due to 1,4-Butanediol diglycidyl ether (BDDE) cross linker. So, the FDA strictly regulated the amount of BDDE usage. This concern leads to interest in biodegradable polymer as the dermal filler. We processed biodegradable PDO micro particle and confirmed its effect as dermal filler application. In order to confirm the in-vivo volume enhancing effect of the PDO filler, it was injected into back skin layer of mouse, and its retention time of enhanced volume was detected. Furthermore, we confirmed collagen regeneration around the injected PDO particle in skin layer. Our PDO filler is currently ongoing clinical trial to confirm its safety and is expected to be approved in KFDA next year.

New classification of late and delayed complications after dermal filler: localized or generalized?

( Hwa Jung Ryu ),( Bo Young Kim ),( Sook In Ryu ),( Song Chang Hwa ),( Joo Yeon Ko ),( Young Suck Ro ),( Il-hwan Kim ),( Jeong Eun Kim ) 대한피부과학회 2020 대한피부과학회 학술발표대회집 Vol.72 No.1

Background: As filler injections have become very common procedures worldwide, the number of complications has increased. However, there is a lack of systematized studies and precise classification of late and delayed complications. Objectives: This study aimed to suggest new and reliable classifications and to characterize the clinical manifestations of late and delayed complications after filler injections. Methods: This retrospective study analyzed patients and suggested a new classification of delayed adverse effects related to filler injection. Several demographic and clinical findings were analyzed. Patients were classified into two types according to their clinical presentation: Type I (Localized) or Type II (Generalized). Results: Twenty-five patients were evaluated during a clinically active adverse event suspected to be related to fillers. The most common injected filler substance was hyaluronic acid (HA, 68.8%). 76% of the patients were classified with Localized complications. In the Generalized complications group, systemic symptoms were more common (p=0.002), the treatment response was poor (p=0.010), and fewer patients showed complete remission (p=0.007) than in the Localized complications group. Conclusion: We propose a simple new classification method for late and delayed complications after dermal filler: Localized and Generalized. We expect that this new classification could help provide appropriate treatment and predict patient prognosis.

Effect of molecular weight of hyaluronic acid (HA) on viscoelasticity and particle texturing feel of HA dermal biphasic fillers

전철병,이득용,Jin-Tae Kim,Mi-Kyung Kwon,Young-Zu Kim,Seok-Soon Kim 한국생체재료학회 2016 생체재료학회지 Vol.20 No.4

Background: Hyaluronic acid (HA) dermal biphasic fillers are synthesized for their efficacy in correcting aesthetic defects such as wrinkles, scars and facial contouring defects. The fillers consist of crosslinked HA microspheres suspended in a noncrosslinked HA. To extend the duration of HAs within the dermis and obtain the particle texturing feel, HAs are crosslinked to obtain the suitable mechanical properties. Results: Hyaluronic acid (HA) dermal biphasic fillers are prepared by mixing the crosslinked HA microspheres and the noncrosslinked HAs. The elastic modulus of the fillers increased with raising the volume fraction of the microspheres. The mechanical properties and the particle texturing feel of the fillers made from crosslinked HA (1058 kDa) microspheres suspended in noncrosslinked HA (1368 kDa) are successfully achieved, which are adequate for the fillers. Conclusions: Dermal biphasic HA fillers made from 1058 kDa exhibit suitable elastic moduli (211 to 420 Pa) and particle texturing feel (scale 7 ~ 9).

Long-Term Side Effects of Soft Tissue Filler Injection

( Sang-min Choi ),( Ki-hun Kim ),( Min-jeong Kang ),( Soon-hyo Kwon ),( Woo-young Sim ),( Bark-lynn Lew ) 대한피부과학회 2023 대한피부과학회지 Vol.61 No.4

Background: Injectable soft tissue fillers are important elements in facial rejuvenation as they provide volume restoration without significant inconvenience to the patient or substantial associated recovery time. Complications can be classified into immediate, delayed, or late adverse reactions. Most complications are temporary and common throughout the filler classes. Objective: To describe the long-term side effects of fillers. Methods: A retrospective study of 10 patients who experienced long-term side effects of soft tissue filler injections between 2007 and 2018 was conducted. A long-term reaction was defined as a complication that occurred 1 year after soft tissue filler injection at any facial site. Results: Ten patients were included in the study. All the patients visited our department because of a palpable subcutaneous nodular lesion on their face. The mean duration from receiving the filler injection to the appearance of side effects was 4.3 years (range, 1∼12 years). Based on their clinicopathological features, complications were roughly classified into granulomatous inflammation (60.0%), non-inflammatory palpable nodule formation (20.0%), abscess (10.0%), and dermal fibrosis with inflammation (10.0%). Conclusion: Regardless of the filler type, side effects can appear up to 12 years after injection. The most common type is a granulomatous lesion; however, it can appear as a non-granulomatous lesion. Therefore, when a patient visits with a nodule or an edematous lesion without any recall reason, careful history taking is needed to find any associated clues. With close follow-up and appropriate treatment, complications associated with injectable soft tissue fillers can be limited and competently managed. (Korean J Dermatol 2023;61(4):233∼238)

미간에 Filler 주입 후 발생한 시력 소실

강유석 ( Yoo Seok Kang ),김지웅 ( Jee Woong Kim ),최우석 ( Woo Seok Choi ),박현수 ( Hyun Su Park ),장상재 ( Sang Jai Jang ),최정철 ( Jung Chul Chio ) 대한피부과학회 2007 대한피부과학회지 Vol.45 No.4

Dermal fillers have been used with increasing frequency over the past three decades in the management of facial lines and atrophic scars and in the correction of facial contours. Injectable soft tissue fillers are ideal for office procedures because of their associated ease, cost, and minimal discomfort. Although complications are rare, they can occur with any dermal filler. However, although most complications are mild and transient, severe, persistent, or recurrent adverse effects can occur. Serious complications include complete or partial visual loss caused by occlusion of a retinal artery. We report a case of a 65-year-old female who experienced sudden visual loss and local necrosis of the glabellar area, secondary to retinal branch artery occlusion, following injection of a filler. Prompt consultation with an ophthalmologist is recommended when there is evidence of visual problem arising after facial injection with dermal fillers. (Korean J Dermatol 2007;45(4):381~383)

Effect of cross-linker chain length on biophysical property of hyaluronic acid hydrogel dermal filler

김문구,Ranjit De,조동철,김선진,최승인,한세광 한국고분자학회 2023 Macromolecular Research Vol.31 No.9

Hyaluronic acid (HA) hydrogels have been widely harnessed for tissue augmentation in plastic surgery, lubrication in knee joint, ocular surgery, and other biomedical applications. The biophysical features of the HA hydrogels are highly depending on the cross-linking agents, which is especially important for the applications to dermal fillers. Here, we investigated the effect of cross-linking chain length of divinyl sulfone (DVS) and 1,4-butanediol diglycidyl ether (BDDE) on the viscoelasticity and retention time of HA hydrogel dermal fillers. After subcutaneous injection of HA-DVS hydrogel dermal filler to rabbits, the safety and stability assessment for a period of 12 weeks revealed that the statistically significant amount of HA-DVS hydrogels remained without any observable change and toxicity. Furthermore, the clinical evaluation demonstrated the equivalence of HA-DVS hydrogels comparable to HA-BDDE hydrogels. There were no clinical abnormal reaction and safety issues. Taken together, we could confirm the clinical feasibility of HA-DVS hydrogel dermal filler with high stability and safety for further clinical applications.

더말 필러(Dermal Filler) 브랜드 패키지디자인의 시각적 요소에 관한 연구

김두한 한국상품문화디자인학회 2019 상품문화디자인학연구 Vol.56 No.-

It is estimated the scale of the domestic market for fillers has grown up to 100 billion won in 2014 from 18.9 billion won in 2009, which is an increase at average 40% every year. The market has shown an outstanding growth for the past five years. The particular causes and structural characteristics that the Korean cosmetic market has may be summarized as follows; first, the highest number of Korean plastic surgeons per capita in the world, and secondly, the direct advertising strategy featuring famous Korean celebrities. This aesthetic trend in pursuit of beauty and youth has last and will last more, and the demand for a facial cosmetic surgery known as the “petit” surgery has kept surging explosively on the basis of increasing concerns on the appearance and the growing “anti-aging” market. First, In this study, we analyze package design of "Dermal Filler" brand by comparing visual factors. Second, we present the direction of package design by understanding the preference of visual elements and flow of purchasing influence through in-depth package interview and focus group interview(FGI). As a result, it was found that each company in this study didn’t show great differentiation in designs for its packaging, but the preference of its brand-logo emphasizing layout to complicated or luxurious graphic designs. The package-designing of “Dermal Filler” must be directed constantly in accordance with its brand imaging and be continuously developed by its brand color to convey the brand and each product’s characteristics. As this study was conducted in order to analyze the graphic facts in brand-packaging, it is to be available as basic data for further development in “Dermal Filler” package-designing to encourage potential purchases. 국내 필러 시장은 2009년 189억 원에서 2014년 1,000억 원으로 연평균 약40% 성장한 것으로 예상된다. 최근 5년간 국내 필러 시장은 압도적인 성장세를 보여주고 있다. 구조적 성장 요인 이외에도 국내 시장의 고유한 특징이 있기 때문이다. 첫 째 세계에서 가장 높은 인구당 피부 및 성형외과 의사 수, 둘째 유명 배우들을 통한 직접적인광고 전략으로 요약된다. 젊음 과 아름다운 외모를 추구하는 트렌드가 지속되고 ‘쁘띠 성형’이라고 알려진 안면미용 시술에 대한 수요는 외모에 대한 관심 증가 및 안티에이징 시장 성장을 기반으로 폭발적으로 증가하고 있다. 본 연구에서는 첫째 더말 필러 브랜드 패키지디자인의 시각적 요소를 비교 분석하고 둘째 FGI와 심층인터뷰를 통해서 시 각적 요소를 통한 선호도와 구매 영향 흐름을 파악하여 패키지디자인의 방향성을 제시한다. 그 결과 각 기업들의 패키지디 자인에서의 차별성이 크지 않다는 것을 알 수 있었고 복잡하고 화려한 그래픽디자인 보다는 제품의 브랜드 로고 중심의 레 이아웃을 선호하는 것을 알 수 있었다. 더말 필러 패키지디자인은 브랜드 이미지와 부합되는 디자인으로 지속적으로 나아 가야하며 브랜드 컬러를 통한 브랜드, 제품별 특징을 더해주고 꾸준히 개발되어야 한다. 본 연구를 통해 도출한 브랜드 패 키지디자인의 시각적 요소를 고려하여 추후 더말 필러 패키지디자인 개발 시 자사 브랜드 제품에 대한 구매를 유도할 수 있는 기초적 자료로 활용이 가능할 것이다.

The Intrinsic Relation between the Hydrogel Structure and In Vivo Performance of Hyaluronic Acid Dermal Fillers: A Comparative Study of Four Typical Dermal Fillers

Zhou Weiwei,Hou Shuai,Deng Shu,Peng Yang,Fu Wei,Zhou Yang,Yang Jie,Peng Cheng 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.3

BACKGROUND: Hyaluronic acid dermal fillers are composed of cross-linked viscoelastic particles with high biocompatibility. The performance of the fillers is determined by the viscoelastic properties of particles and the connecting force between particles. However, the relationships among the properties of fillers, the interaction of the gels and the surrounding tissue are not clear enough. METHOD: Four kinds of typical dermal filler were selected in this research to reveal the interaction between the gels and cells. A series of analytical tools was applied to characterize the structure and physicochemical properties of the gel, as well as observing their interaction with the surrounding tissues in vivo and discussing their internal mechanism. RESULT: The large particles internal the gel and the high rheological properties endow the Restylane2 with excellent support. However, these large-size particles have a significant impact on the metabolism of the local tissue surrounding the gel. Juve´derm3 present gel integrity with the high cohesiveness and superior support. The rational matching of large and small particles provides the Juve´derm3 with supporting capacity and excellent biological performance. Ifresh is characterized by small-size particles, moderate cohesiveness, good integrity, lower viscoelasticity and the superior cellular activity located the surrounding tissues. Cryohyaluron has high cohesion and medium particle size and it is prominent in cell behaviors involving localized tissues. Specific macroporous structure in the gel may facilitate the nutrients delivering and removing the waste. CONCLUSION: It’s necessary to make the filler both sufficient support and biocompatibility through the rational matching of particle sizes and rheological properties. Gels with macroporous structured particle showed an advantage in this area by providing a space inside the particle.