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1.
BACKGROUND: Acne scar correction remains a challenge to the dermatologic surgeon. With nonablative laser resurfacing, this correction is imputed to dermal collagen remodeling and acne scar reorganization. Although atrophic acne scars tend to respond to laser treatment, the deeper ice pick and boxcar scars tend to be laser resistant. OBJECTIVE: To investigate the treatment of atrophic and a mixed pattern of facial acne scars, we evaluated a 1320-nm Nd:YAG laser. Twelve subjects with atrophic facial acne scars (N=6) or a combination of atrophic and pitted, sclerotic, or boxcar scars (N=6) received three laser treatments. Physician and patient acne scar ratings were performed at baseline and at 6 months after the last treatment. Acne scars were rated with a 10-point severity scale. RESULTS: Mean acne scar improvement was 1.5 points on physician assessments (P=0.002) and 2.2 points on patient assessments (P=0.01). Acne scars were rated more severely by patients than by the physician at all intervals. There were no noted complications at 6 months. CONCLUSION: The 1320-nm Nd:YAG laser is a safe and effective nonablative modality for the improvement of atrophic and a mixed pattern of facial acne scars.  相似文献   

2.
Autologous cultured fibroblasts: a protein repair system   总被引:13,自引:0,他引:13  
Cultured autologous fibroblasts create a living injectable system that has been utilized effectively to treat rhytids, depressed scars, subcutaneous atrophy, acne irregularities, and laser wounds. Autologous cultured fibroblasts (Isolagen) as a protein repair system is produced from a 3-mm cutaneous punch biopsy. Skin biopsies are initiated in an in vitro tissue culture system. The cells are expanded to produce large quantities of fibroblasts and extracellular matrix totaling 1.0 to 1.5 ml. This cellular system is injected into the patient after 8 weeks of cellular expansion. Each area of treatment is injected once every 2 weeks for three injections. A total of 1,450 patients in the United States and Europe have been treated at designated centers. A total of 4,800 injections were given. At the University of Medicine and Dentistry of New Jersey and Hackensack University Medical Center, 94 patients were treated from 1995 through 1999. Long-term follow-up ranged from 36 to 48 months. A subjective patient satisfaction survey showed 92% of the patients were satisfied with the grade of correction. A long-term follow-up survey revealed continuing improvement beyond the initial correction in 70% of patients. Results from other designated centers correlated with the authors' findings. Cultured autologous fibroblasts (Isolagen) appears to be a living, cellular, dynamic filler system capable of immediate correction and continued repair of dermal and superficial subcutaneous deficiencies.  相似文献   

3.
目的:探讨自体脂肪移植修复面部凹陷性及萎缩性瘢痕的方法和临床疗效。方法:对10例面部凹陷性及萎缩性瘢痕患者采用自体脂肪移植进行治疗。脂肪获取、提纯及注射采用3M3L移植技术。每例自体脂肪移植1~3次,每次间隔3~6个月,综合评价患者术后面部轮廓畸形、瘢痕皮肤质地改善情况。结果:患者均获随访3个月~1年,无感染、囊肿、钙化、血管和神经损伤等并发症发生,也未产生新畸形及新瘢痕。轮廓凹陷畸形得到矫正,瘢痕皮肤质地及色泽有所改善,患者均对治疗效果满意。结论:自体脂肪移植是一种治疗面部凹陷性及萎缩性瘢痕可行的微创方法。  相似文献   

4.
OBJECTIVES: To develop a canine model of vocal fold scar and to evaluate its treatment with lamina propria replacement therapy using autologous cultured fibroblasts. MATERIALS AND METHODS: Full thickness of the lamina propria layer in canine vocal folds was injured with a laser. Fibroblasts were cultured and expanded in the laboratory from a buccal mucosal biopsy. The scarred vocal folds were treated with 3 weekly injections of fourth, fifth, and sixth passage autologous fibroblasts. Mucosal waves and acoustic parameters were measured at baseline, after scarification, and several months after injection therapy. Histologic evaluation of the vocal folds for fibroblasts, collagen, elastin, reticulin, and hyaluronic acid was performed. RESULTS: Nine beagle dogs were used, and 1 animal served as control. Vocal fold scarring resulted in absent or severely limited mucosal waves and significantly worse acoustic parameters. Significant improvements in mucosal waves and acoustic parameters were obtained after lamina propria replacement therapy. After therapy, mucosal waves became normal in 4 animals and near normal in the other 4. No statistical difference was found in mucosal waves between baseline and post-therapy. All animals tolerated therapy without complications. The treated vocal folds demonstrated an increased density of fibroblasts, collagen, and reticulin, a decreased density of elastin, and no change in hyaluronic acid. CONCLUSIONS AND SIGNIFICANCE: Therapeutic options for vocal fold scars are limited. Lamina propria replacement therapy in the form of autologous cultured fibroblasts improves mucosal pliability and returns normal or near normal mucosal waves in experimentally scarred vocal folds. This novel therapeutic modality may hold new promise for treating vocal fold scars.  相似文献   

5.
Autologous cultured fibroblasts as cellular therapy in plastic surgery   总被引:8,自引:0,他引:8  
Autologous cultured fibroblasts serve as injectable protein repair systems for correction of acne scars, rhytids, and other facial scars. The system uses the patient's own cultured fibroblasts to correct contour deformities over time.  相似文献   

6.
YONG-KWANG TAY  MD    COLIN KWOK  MD 《Dermatologic surgery》2008,34(5):681-685
BACKGROUND Atrophic scars are dermal depressions caused by collagen damage most commonly occurring after inflammatory acne vulgaris. There are little published data regarding the effectiveness and safety of minimally invasive lasers in the treatment of atrophic acne scars in darker skin types.
OBJECTIVE The purpose was to evaluate the efficacy and safety of a low-fluence 2,940-nm erbium:YAG laser in the treatment of atrophic acne scars in Asian patients.
MATERIALS AND METHODS Nine patients aged 19 to 45 years with mild to moderate atrophic facial scars and Skin Types IV and V were treated with topical anesthesia and one to two passes with an erbium:YAG laser two times at 1-month intervals. Treatment parameters were 6-mm spot size, fluence of 400 mJ, pulse duration of 300 μs, and repetition rate of 2 Hz.
RESULTS At 2 months after the last treatment, mild to moderate clinical improvement was noted in all patients compared to baseline. Treatment was well tolerated. Side effects consisted of posttreatment erythema, peeling, and crusting, which resolved within 1 to 2 weeks. There was no postinflammatory hyper- or hypopigmentation, blistering, or hypertrophic scarring.
CONCLUSION Low-fluence erbium:YAG facial resurfacing was effective and safe in patients with mild to moderately severe atrophic acne scarring.  相似文献   

7.
BACKGROUND: The recent development of high-energy pulsed CO2 lasers that minimize thermal injury to uninvolved adjacent structures has revolutionized the manner in which atrophic facial scars are recontoured. Significant improvement of atrophic scars with laser resurfacing has clearly been demonstrated; however, the exact timing for assessment of skin for further treatment has varied due to the unknown amount of time needed after laser scar resurfacing to effect maximal collagen formation and remodeling. OBJECTIVE: The aim of this study was to determine the immediate and long-term (12-18 months) histologic and clinical effects of atrophic acne scars after CO2 laser resurfacing in order to provide physician guidelines for postoperative clinical assessment for retreatment. METHODS: Sixty patients (50 women, 10 men, mean age 38 years, skin types I-V) with moderate to severe atrophic facial scars were evaluated. Nineteen patients received regional cheek treatment and 41 patients received full-face resurfacing with a high-energy pulsed CO2 laser. Independent clinical assessments of treated scars were performed at 1, 6, 12, and 18 months and blinded histologic analyses were made of skin biopsies immediately prior to and after laser resurfacing, and at 1, 6, 12, and 18 months postoperatively in six patients. RESULTS: Significant immediate and prolonged clinical improvement in skin tone, texture, and appearance of CO2 laser-irradiated scars was seen in all patients. Average clinical improvement scores were 2.22 (69%) at 1 month, 2.1 (67%) at 6 months, 2.37 (73%) at 12 months, and 2.5 (75%) at 18 months. Continued collagenesis and subsequent dermal remodeling were observed on histologic examination of biopsied tissue up to 18 months after surgery. CONCLUSION: Continued clinical improvement was observed as long as 18 months after CO2 laser resurfacing of atrophic scars, with an 11% increase in improvement observed between 6 and 18 months postoperatively. We propose that a longer postoperative interval (12-18 months) prior to assessment for re-treatment be advocated in order to permit optimal tissue recovery and an opportunity for collagen remodeling.  相似文献   

8.
PURPOSE: We evaluated the effectiveness of periurethral autologous fat injection as treatment for female stress urinary incontinence. MATERIALS AND METHODS: Women with stress incontinence were randomized in a double-blind fashion to receive periurethral injections of autologous fat (treatment group) or saline (placebo group). After injection patients were evaluated monthly for 3 months by a validated standardized incontinence questionnaire, 1-hour pad test and cough test. Patients who remained incontinent were offered repeat injection using the same initial agent to a maximum of 3 injections. Every 3 months after injection patients were assessed by a standardized questionnaire, pad test, cough test and urodynamics. Those who did not qualify for repeat injection at 3 months were then followed 6, 9, 12, 18 and 24 months or until failure. RESULTS: Of the 68 women enrolled 35 received fat and 33 received saline injections. The groups were comparable in terms of baseline parameters. A total of 56 patients completed the study, including 27 in the fat and 29 in the placebo group, for a total of 189 injections (91 fat and 98 saline). At 3 months 6 of 27 (22.2%) and 6 of 29 (20.7%) women were cured or improved in the fat and saline groups, respectively. Complications included cystitis in 9 of 189 injections, urinary retention in 6 in the fat injection group, urge incontinence in 9 of 68 patients and pulmonary fat embolism resulting in death in 1 of 189 procedures. CONCLUSIONS: In this study periurethral fat injection did not appear to be more efficacious than placebo for treating stress incontinence.  相似文献   

9.
目的注射移植自体成纤维细胞为面部微小凹陷和皱纹的治疗提供了一种新方法。探讨在对细胞存活性研究的基础上,成纤维细胞在体外环境传代下的遗传性状的安全问题。方法采用核型分析和流式细胞仪计数,对5例女性、3例男性的第5代和第10代细胞的遗传性状进行了研究。结果第5代和第10代成纤维细胞均呈正常的二倍体核型,无异常核型的改变;细胞周期分析,均呈良好的同步性,未出现细胞凋亡现象。结论人皮肤成纤维细胞体外传代在10代以内,无遗传性状的改变,作为移植的种子细胞是安全的。  相似文献   

10.
Mechanisms for keloid formation include drastic changes in growth factor actions, collagen turnover, mechanical forces applied over the skin, and genetic and immunologic contributions. The use of corticosteroids to manage keloids increases basic fibroblast growth factor production while decreasing transforming growth factor-beta1 production by human dermal fibroblasts, endogenous vascular endothelial growth factor, and insulin-like growth factor-1. The use of corticosteroid injections is, to date, the core treatment available for the management of excessive tissue production in scars. Currently, the most effective and safe regimen for keloid management appears to be the use of corticotherapy-injection of intradermal steroids after a surgical excision.  相似文献   

11.
Acne vulgaris affects up to 80% of people 11 to 30 years of age, and scarring can occur for up to 95% of these patients. Scarring may be pitted or hypertrophic in nature, although in most cases it is atrophic. Atrophic acne scarring follows dermal collagen and fat loss after moderate to severe acne infection. Injectable poly-L-acid (PLLA) is a biocompatible, biodegradable, synthetic polymer device that is hypothesized to enhance dermal volume via the endogenous production of fibroblasts and, subsequently, collagen. The gradual improvements in cutaneous volume observed after treatment with injectable PLLA have been noted to last up to 2 years. The case studies presented describe the use of injectable PLLA to correct dermal fat loss in macular atrophic acne scarring of the cheeks. Two female patients underwent three treatment sessions with injectable PLLA over a 12-week period. At each treatment session, the reconstituted product was injected into the deep dermis under the depressed portion of the scar. Both patients were extremely pleased with their results at, respectively, 1- and 4-year follow-up evaluations. Patients experienced minimal swelling and redness after injection and no product-related adverse events such as papule and/or nodule formation. The author believes these data suggest that injectable PLLA is a good treatment option for the correction of macular atropic scarring with thin dermis (off-label use), particularly compared with other injectable fillers currently used for this indication that have shorter durations of effect.  相似文献   

12.
BACKGROUND: Atrophic scars of the forehead can result from various pathologic processes including morphea en coup de sabre as well as trauma. A variety of surgical techniques can be used to correct these atrophic scars. OBJECTIVE: Soft tissue augmentation for correction of atrophic scars of the forehead using en bloc autologous dermal fat graft. METHODS: Use of en bloc autologous dermal fat graft harvested from the hip and inserted into a pocket created under the atrophic scar in two patients with depressed scars of the forehead. RESULTS: Overcorrection of the scars with en bloc autologous dermal fat grafts resulted in the treated areas becoming level with the adjacent skin within 3 months. Follow-up for a period of 12 months showed a perfectly level and stable graft with no further resorption. CONCLUSION: En bloc autologous dermal fat grafting appears to be a safe technique that provides excellent cosmetic results for the correction of small to medium depressed scars of the forehead.  相似文献   

13.
Although the conventional, short-pulsed erbium: yttrium-aluminum-garnet (Er:YAG) laser provides substantial clinical improvement for pitted, facial acne scars, it shows less effective hemostasis and limited residual thermal effect in the dermis. Recently, dual-mode Er:YAG laser systems with both ablation and coagulation modes have been developed. The purpose of this study was to evaluate the clinical and histologic effects of resurfacing pitted, facial acne scars with a dual-mode Er:YAG laser. Twenty patients with pitted facial acne scars underwent laser resurfacing using a computerized-scanning, dual-mode Er:YAG laser. All patients had Fitzpatrick skin types ranging III–V. Initially, the epidermis was removed in two passes using the ablative settings. This step was followed by two passes in a mixed ablation and coagulation mode, to produce further ablation and controlled, residual thermal damage. A final pass in a ablation mode was used to remove necrotic tissue. Laser overlapping was approximately 30%. The results of laser treatment were evaluated for the degree of clinical improvement, duration of erythema, pigmentary change, and any adverse events at two weeks, one month, and three months. In two patients, skin biopsies were obtained at the following intervals: immediately and two weeks postoperatively for histologic examination. There was a 75% average clinical improvement observed in pitted, facial acne scars after laser treatment. Complete wound healing occurred between six and eight days. On histologic examination, complete re-epithelialization was observed at two weeks. Erythema occurred in all patients after laser treatment and lasted longer than three months in 10 patients (50%). Post-inflammatory hyperpigmentation occurred in 12 patients (60%) two to four weeks after laser treatment and lasted longer than three months in one patient (5%). One patient (5%) experienced mild hypopigmention. Mild to moderate, postoperative acne flare-up occurred in seven patients (35%). No other adverse effects were observed. In conclusion, resurfacing with a dual-mode Er:YAG laser is a safe and effective treatment modality for pitted, facial acne scars.  相似文献   

14.
For the elimination of facial wrinkles and skin contour defects, injectable filler substances composed of commercially prepared nonanimal stabilized hyaluronic acid (Restylane) are now widely used. Although this method of suspension has been shown to be relatively safe and convenient, varying degrees of resorption have required repeated percutaneous injections. This study was undertaken to evaluate the feasibility of Restylane, which is a modified hyaluronic acid, combined with cultured human dermal fibroblasts, to enhance the longevity of injected implants. The histologic changes of the injected implants were also evaluated. For the test group, fibroblasts from the dermis of healthy adults were isolated and cultivated. The cultured fibroblasts were measured with a hemocytometer. Five x 105 fibroblasts suspended in 200 microl of Dulbecco phosphate-buffered saline (DPBS) were then dispersed in 200 microl of Restylane to form a 400-microl human fibroblast-Restylane mix. For the control group, 200 microl of DPBS without fibroblasts were mixed with 200 microl of Restylane. These implants were subcutaneously injected into the back of an athymic nude mouse at 6 sites, the 3 left sites composing the control group and the 3 right sites composing the test group. Twelve nude mice were injected for a total of 36 injections per group. The nodular swellings that resulted from the injections were excised to include skin beyond the swelling points down to the panniculus carnosus layer using 5-mm punches, and the weights were measured at 1, 2, 4, 8, 12, and 16 weeks after the injections. Histologic comparisons were also performed to confirm the presence of human collagen in the fibroblast-mixed Restylane group using immunohistochemical study with antihuman collagen type I polyclonal antibody. The mean weight of the control group nodules decreased throughout the examination period. The mean weight at the 16th week was 60% of the weight at the first week. On the other hand, the mean weight of the test-group nodules decreased only over the first 2 weeks. Beyond 2 weeks, there was no further significant weight change. The mean weight at the 16th week was 91% of the weight measured at the first week. Histologic examinations of the control group exhibited negative immunohistochemical staining for human collagen at each examination period. The test group exhibited positive staining after 2 weeks, indicating the presence of human collagen. These results indicate that Restylane mixed with cultured human dermal fibroblasts may be successfully injected as living grafts for long-term retention of implants.  相似文献   

15.
SUNG BIN CHO  MD    CHANG OOK PARK  MD    WOO GIL CHUNG  MD    KWANG HOON LEE  MD  PHD    JUNG BOCK LEE  MD  PHD    KEE YANG CHUNG  MD  PHD 《Dermatologic surgery》2006,32(10):1231-1236
BACKGROUND: Atrophic scars can be induced by various causes, including severely inflamed acne, chicken pox, and trauma. Many treatment modalities are used for reconstructing and improving the appearance of scars with various treatment results. OBJECTIVE: A recent report shows the clinical efficacy of the chemical reconstruction of skin scars (CROSS) method, which consists of the focal application of trichloroacetic acid (TCA) in a higher concentration. Histometric analysis of the CROSS method, however, has not yet been established. METHODS: In this study, five hairless mice were used to evaluate the effect of the CROSS method and to analyze the difference between the CROSS method and simple TCA application. RESULTS: Similar histologic changes were observed in the two methods, including epidermal and dermal rejuvenation with new collagen deposition. These changes, however, were more prominent in the CROSS method-treated areas, particularly when 100% TCA was used. CONCLUSION: The results of this study suggest that treatment of atrophic scars using the CROSS method is more effective than simple application of TCA in activating fibroblasts in the dermis and increasing the amount of collagen.  相似文献   

16.
Nita Patel  MD    Marc Clement  PhD 《Dermatologic surgery》2002,28(10):942-945
BACKGROUND: Selective nonablative wrinkle reduction with low-fluence pulsed dye laser has been shown to provide cosmetic benefits by stimulating the production of dermal collagen. The clinical efficacy for improving the appearance of acne scarring using selective nonablative laser treatments has yet to be established. OBJECTIVE: To evaluate the improvement in the appearance and topography of acne scarring following application of a 585 nm pulsed dye laser with a temporal profile and pulse duration designed specifically to target healthy microvasculature in the dermis. METHODS: Ten patients (mean age 34.8 years) with Fitzpatrick skin types I-IV and shallow to moderately deep, saucerized facial acne scars were enrolled in a prospective trial to receive a single laser treatment of both cheeks. Patients were evaluated at 30, 60, 90, and 120 days to assess the degree of clinical improvement. The evaluation process included assessment of pre- and posttreatment photography by two independent observers, patient assessment surveys, and surface profilometry using silicone imprints in order to quantify the degree of clinical improvement. RESULTS: All 10 patients reported visible cosmetic improvement in the treated areas while surface profilometry showed that, on average, the depth of the acne scars was reduced by 47.8%. No adverse effects of this treatment were reported. CONCLUSION: The treatment of acne scars utilizing a 585 nm pulsed dye laser with a temporal profile and pulse duration designed specifically to target healthy microvasculature in the dermis may be a safe and effective noninvasive alternative for a natural result.  相似文献   

17.
BACKGROUND: Effective treatment of facial acne scarring presents a major challenge. Nonablative lasers and radiofrequency devices work by thermally stimulating dermal collagen remodeling, thereby softening acne scars in a minimally invasive fashion. One such laser, a 1,064-nm short-pulsed Nd:YAG, uses rapidly scanned low-energy infrared pulses to heat the dermis selectively through the normal dermal microvasculature. OBJECTIVE: In this pilot study, the safety and efficacy of a novel short-pulsed Nd:YAG laser were investigated for the treatment of moderate to severe facial acne scarring. MATERIALS AND METHODS: Nine of 10 enrolled patients with moderate to severe facial acne scarring received eight sequential 1,064-nm Nd:YAG treatments (laser parameters 14 J/cm2, 0.3 milliseconds, 5-mm spot size, 7-Hz pulse rate, 2,000 pulses per side of face). Patients were graded for the presence and severity of three scar morphologies: superficial (rolling), medium-depth (boxcar), and deep (ice pick). Outcome measures included blinded evaluation of before and after photographs by three physician observers (scar severity score) and patient self-assessment. RESULTS: Acne scarring improved in 100% of the nine patients completing the study. Scar severity scores improved by a mean of 29.36% (95% confidence interval, 16.93%-41.79%; p = .006); 89% of patients noted greater than 10% scar improvement. No treatment-related adverse events were seen. CONCLUSION: Our findings support the use of a short-pulsed, low-fluence 1,064-nm Nd:YAG laser as a safe, effective treatment for facial acne scarring. Scar improvement was noted in all treated subjects with minimal discomfort and no downtime. This protocol appears to be most effective at reducing scar depth and softening scar contours. A laser upgrade needed for the study was provided to the authors at a reduced price.  相似文献   

18.
Bio-Alcamid (Polymekon, Italy) is a relatively new, injectable soft tissue endoprosthesis that is recommended for correcting soft tissue defects and contour deformities. It consists of 96% water and 4% synthetic polymeric polyalkylimide, and once injected becomes enclosed within a thin collagen capsule. MATERIALS AND METHOD: We have treated a selected series -- 34 patients, 57 anatomical sites treated in 64 treatment sessions, with a range of 2.5 ml to 110 ml injected per site per injection. The indications have been as diverse as anti-retrovirus treatment associated facial lipoatrophy, pectus excavatum and post-breast reconstruction contour deformities. The patients were followed up in clinics and through a postal questionnaire survey. RESULTS: The longest follow up we have now is over eighteen months. The results have been uniformly good and satisfactory to both patients and the surgeon. The patients tolerated the treatment very well under local anaesthesia. The questionnaire survey showed universally high degrees of satisfaction. The biggest advantages of Bio-Alcamid over other filler injections have been permanency of volume correction and a very natural soft feel of the treated areas. Many patients required a single treatment only to correct significant volume defects. CONCLUSION: In our experience, Bio-Alcamid is safe and fulfils most of the criteria of an ideal injectable filler material.  相似文献   

19.
In the last years preclinical studies have paved the way for the use of adult muscle derived stem cells for reconstruction of the lower urinary tract. Between September 2002 and October 2004, 42 women and 21 men suffering from urinary stress incontinence (age 36–84 years) were recruited and subsequently treated with transurethral ultrasonography-guided injections of autologous myoblasts and fibroblasts obtained from skeletal muscle biopsies. The fibroblasts were injected into the urethral submucosa, while the myoblasts were implanted into the rhabdosphincter. In parallel, 7 men and 21 women (age 39–83 years) also diagnosed with urinary stress incontinence were treated with standard transurethral endoscopic injections of collagen. Patients were randomly assigned to both groups. After a follow-up of 12 months incontinence was cured in 39 women and 11 men after injection of autologous myoblasts and fibroblasts. Mean quality of life score (51.38 preoperatively, 104.06 postoperatively), thickness of urethra and rhabdosphincter (2.103 mm preoperatively, 3.303 mm postoperatively) as well as contractility of the rhabdosphincter (0.56 mm preoperatively, 1.462 mm postoperatively) were improved postoperatively. Only in two patients treated with injections of collagen incontinence was cured. The present clinical results demonstrate that, in contrast to injections of collagen, urinary incontinence can be treated effectively with ultrasonography-guided injections of autologous myo- and fibroblasts.  相似文献   

20.
Background. This article addresses the use of liquid injectable silicone as both an immediate and long-lasting treatment for broad-based, depressed acne scars. The only filler substance that maintains precision and permanence in improving and/or correcting these types of acne scar defects is medical-grade liquid silicone.
Objective. We describe five patients with a history of acne scarring who showed improvements from injections of liquid silicone at the initial treatment session and lasting over a 10-, 15-, and 30-year follow-up period.
Methods. Monthly liquid silicone injections using a technique known as the microdroplet, multiple-injection approach.
Results. This article documents the safety, effectiveness, and precision of silicone in addition to highlighting the fact that its permanence is what distinguishes it from other filler materials.
Conclusion. As a precise and permanent filling substance used for soft tissue augmentation, liquid injectable silicone can improve and/or eliminate depressed, broad-based acne scars through a technique known as the microdroplet, multiple-injection approach.  相似文献   

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