Combined dasatinib and quercetin treatment contributes to skin rejuvenation through selective elimination of senescent cells in vitro and in vivo.

The skin's protective functions are compromised over time by both endogenous and exogenous aging. Senescence is well-documented in skin phenotypes, such as wrinkling and sagging, a consequence of the senescence-associated secretory phenotype (SASP) that involves the accumulation of senescent fibroblasts, chronic inflammation, and collagen remodeling. Although therapeutic approaches for eliminating senescent cells from the skin are available, their efficacy remains unclear. Accordingly, we aimed to examine the effects of dasatinib in combination with quercetin (D + Q) on senescent human skin fibroblasts and aging human skin. Senescence was induced in human dermal fibroblasts (HDFs) using approaches such as long-term passaging, ionizing radiation, and doxorubicin treatment. The generated senescent cells were treated with D + Q or vehicle. Additionally, a mouse-human chimera model was generated by subcutaneously transplanting whole-skin grafts of aged individuals onto nude mice. Mouse models were administered D + Q or vehicle by oral gavage for 30 days. Subsequently, skin samples were harvested and stained for senescence-associated beta-galactosidase. Senescence-associated markers were assessed by western blotting, reverse transcription-quantitative PCR and histological analyses. Herein, D + Q selectively eliminated senescent HDFs in all cellular models of induced senescence. Additionally, D + Q-treated aged human skin grafts exhibited increased collagen density and suppression of the SASP compared with control grafts. No adverse events were observed during the study period. Collectively, D + Q could ameliorate skin aging through selective elimination of senescent dermal fibroblasts and suppression of the SASP. Our findings suggest that D + Q could be developed as an effective therapeutic approach for combating skin aging.

Regulation of ENPP5, a senescence-associated secretory phenotype factor, prevents skin aging.

Aging negatively affects the appearance and texture of the skin owing to the accumulation of senescent fibroblasts within the dermis. Senescent cells undergo abnormal remodeling of collagen and the extracellular matrix through an inflammatory histolytic senescence-associated secretory phenotype (SASP). Therefore, suppression of SASP in senescent cells is essential for the development of effective skin anti-aging therapies. Ectonucleotide pyrophosphatase/phosphodiesterase family member 5 (ENPP5), an extracellular signaling molecule, has been implicated in vascular aging and apoptosis; however, its role in SASP remains unclear. Therefore, this study aimed to investigate the role of ENPP5 in SASP and skin aging using molecular techniques. We investigated the effects of siRNA-mediated ENPP5 knockdown, human recombinant ENPP5 (rENPP5) treatment, and lentiviral overexpression of ENPP5 on SASP and aging in human skin fibroblasts. Additionally, we investigated the effect of siRNA-mediated ENPP5 knockdown on the skin of C57BL/6 mice. We found that ENPP5 was significantly expressed in replication-aged and otherwise DNA-damaged human skin fibroblasts and that treatment with human rENPP5 and lentiviral overexpression of ENPP5 promoted SASP and senescence. By contrast, siRNA-mediated knockdown of ENPP5 suppressed SASP and the expression of skin aging-related factors. Additionally, ENPP5 knockdown in mouse skin ameliorated the age-related reduction of subcutaneous adipose tissue, the panniculus carnosus muscle layer, and thinning of collagen fibers. Conclusively, these findings suggest that age-related changes may be prevented through the regulation of ENPP5 expression to suppress SASP in aging cells, contributing to the development of anti-aging treatments for the skin.

Fisetin, a potential skin rejuvenation drug that eliminates senescent cells in the dermis.

Accumulation of senescent fibroblasts, chronic inflammation, and collagen remodeling due to aging-related secretory phenotypes have been hypothesized to cause age-related skin aging, which results in wrinkles and loss of skin elasticity, thus compromising appearance attractiveness. However, the rejuvenating effects of removing senescent cells from the human skin and the efficacy of related therapeutic agents remain unclear. Here, we investigated the effects of fisetin, a potential anti-aging component found in various edible fruits and vegetables, on senescent human dermal fibroblasts (HDFs) and aging human skin. Senescence was induced in primary HDFs using long-term passaging and treatment with ionizing radiation, and cell viability was assessed after treatment with fisetin and a control component. A mouse/human chimeric model was established by subcutaneously transplanting whole skin grafts from aged individuals into nude mice, which were treated intraperitoneally with fisetin or control a component for 30 d. Skin samples were obtained and subjected to senescence-associated-beta-galactosidase staining; the extent of aging was evaluated using western blotting, reverse transcription-quantitative PCR, and histological analysis. Fisetin selectively eliminated senescent dermal fibroblasts in both senescence-induced cellular models; this effect is attributable to cell death induction by caspases 3, 8, and 9-mediated endogenous and exogenous apoptosis. Fisetin-treated senescent human skin grafts showed increased collagen density and decreased senescence-associated secretory phenotypes (SASP), including matrix metalloproteinases and interleukins. No apparent adverse events were observed. Thus, fisetin could improve skin aging through selective removal of senescent dermal fibroblasts and SASP inhibition, indicating its potential as an effective novel therapeutic agent for combating skin aging.

Preoperative photoacoustic versus indocyanine green lymphography in lymphaticovenular anastomosis outcomes for lower extremity lymphedema: A pilot study.

BACKGROUND: Identification of the proper lymphatics is important for successful lymphaticovenular anastomosis (LVA) for lymphedema; however, visualization of lymphatic vessels is challenging. Photoacoustic lymphangiography (PAL) can help visualize lymphatics more clearly than other modalities. Therefore, we investigated the usefulness of PAL and determined whether the clear and three-dimensional image of PAL affects LVA outcomes. METHODS: We recruited 22 female patients with lower extremity lymphedema. The operative time, number of incisions, number of anastomoses, lymphatic vessel detection rate (number of functional lymphatics identified during the operation/number of incisions), and limb volume changes preoperatively and 3 months postoperatively were compared retrospectively. The patients were divided according to whether PAL was performed or not, and results were compared between those undergoing PAL (PAL group; n = 10) and those who did not (near-infrared fluorescence [NIRF] group, n = 12). RESULTS: The mean age of the patients was 55.9 ± 15.1 years in the PAL group and 50.7 ± 14.9 years in the NIRF group. One patient in the PAL group and three in the NIRF group had primary lymphedema. Eighteen patients (PAL group, nine; and NIRF group, nine) had secondary lymphedema. Based on preoperative evaluation using the International Society of Lymphology (ISL) classification, eight patients were determined to be in stage 2 and two patients in late stage 2 in the PAL group. In contrast, in the NIRF group, one patient was determined to be in stage 0, three patients each in stage 1 and stage 2, and five patients in late stage 2. Lymphatic vessel detection rates were 93% (42 LVAs and 45 incisions) and 83% (50 LVAs and 60 incisions) in the groups with and without PAL, respectively (p = 0.42). Limb volume change was evaluated in five limbs of four patients and in seven limbs of five patients in the PAL and NIRF groups as 336.6 ± 203.6 mL (5.90% ± 3.27%) and 52.9 ± 260.7 mL (0.71% ± 4.27%), respectively. The PAL group showed a significant volume reduction. (p = .038). CONCLUSIONS: Detection of functional lymphatic vessels on PAL is useful for treating LVA.

Hemostatic Efficacy of Oxidized Regenerated Cellulose Powder in Le Fort 1 Osteotomy.

A challenging aspect of Le Fort I osteotomy is bleeding control. Osteotomy techniques, devices, drugs, and anesthetic management have been reported to reduce bleeding; however, there are no reports on the use of hemostatic agents. We aimed to evaluate the hemostatic efficacy of a new topical absorbent hemostatic agent, Surgicel Powder, consisting of oxidized regenerated cellulose (ORC). We reviewed the records of 40 patients who underwent Le Fort I surgery for jaw deformities, with or without cleft lip and palate. Twenty of the 40 patients did not have cleft lips or cleft palates (CLCP); the remaining 20 had CLCP. In each group, an absorbent hemostatic agent was used in 10 patients but not in the other 10. Total blood loss and operative time for each group were evaluated. In the jaw deformity without CLCP group, the amount of bleeding with or without ORC was 112.0±33.8 and 158.6±75.3 mL, respectively, with a significant difference between groups ( P <0.05). Operative time with or without ORC was 206.4±31.3 and 238.3±42.5 minutes, respectively, with a significant difference observed between groups ( P <0.05). In the jaw deformity with CLCP group, the amount of bleeding with or without ORC was 199.7±64.6 and 476.8±104.8 mL, respectively, with a significant difference between groups ( P <0.05). Operative time with or without ORC was 213.7±27.6 and 220.8±41.5 minutes, respectively, with no significant difference between groups ( P =0.329). In conclusion, oxidized regenerated cellulose powder may be a beneficial hemostatic agent for reducing blood loss during Le Fort I osteotomy.

Three-dimensional adipofascial and dermal structures involved in forehead crease formation.

Deeply etched forehead creases indicate aging. Various treatments such as filler injections, fat grafting, and facelift surgery are used to remove them. However, knowledge of the anatomical structures associated with subcutaneous tissue changes and the superficial musculoaponeurotic system is lacking, and there is no consensus about the appropriate treatment. We have investigated the subcutaneous structures involved in forehead creases; this will help to establish selection criteria for improved treatment. The forehead sections of five unfixed adult Asian cadavers were obtained. Tissues containing forehead creases were removed from the periosteum and were examined using gross observation, radiography, histology, and nano-computed tomography. All methods revealed that the dermis in the skin crease area, namely the fold visible from the body surface, was bound to the frontalis muscle by a three-dimensional fibrous structure between the fatty septa. This structure was dense near the skin folds and sparse and thin in other areas. In particular, it was tightly bound to the dermis immediately below the crease, with collagen fibers traversing toward the epidermis. In addition, there were fewer skin appendages near the crease than in the normal area, or they were absent altogether; the epidermis was thicker, and the dermal papillae were more developed. It is thought that the density and firmness of the fibrous fatty septal structures between the dermis-frontalis muscle and the specific structures of the epidermis and dermis immediately below the crease account for the characteristic plastic forehead creases.

Identification of resibufogenin, a component of toad venom, as a novel senolytic compound in vitro and for potential skin rejuvenation in male mice.

Senescent cells that accumulate with age have been shown to contribute to age-related diseases and organ dysfunction and have attracted attention as a target for anti-aging therapy. In particular, the use of senescent cell-depleting agents, or senolytics, has been shown to improve the aging phenotype in animal models. Since senescence has been implicated in the skin, particularly in fibroblasts, this study used aged human skin fibroblasts to investigate the effects of resibufogenin. A component of the traditional Chinese medicine toad venom, resibufogenin was investigated for senolytic and/or senomorphic activity. We found that the compound selectively caused senescent cell death without affecting proliferating cells, with a marked effect on the suppression of the senescence-associated secretory phenotype. We also found that resibufogenin causes senescent cell death by inducing a caspase-3-mediated apoptotic program. Administration of resibufogenin to aging mice resulted in an increase in dermal collagen density and subcutaneous fat, improving the phenotype of aging skin. In other words, resibufogenin ameliorates skin aging through selective induction of senescent cell apoptosis without affecting non-aged cells. This traditional compound may have potential therapeutic benefits in skin aging characterized by senescent cell accumulation.

Measurement of lymphatic vessel depth using photoacoustic imaging.

OBJECTIVES: Information regarding the depth of lymphatic vessel is important for lymphatic surgeons because rapid identification of functional lymphatic vessels and veins is necessary to perform good lymphaticovenular anastomosis, which is a surgical procedure for lymphedema cases. Photoacoustic lymphangiography (PAL) may be useful for such identification because it allows the assessment of the depth of lymphatic vessels. Thus, we aimed to measure the lymphatic vessel depth using images obtained by PAL. METHODS: This study included healthy individuals and patients with lymphedema. In all participants, indocyanine green dissolved in dextrose was injected subcutaneously into the first and fourth webs of the foot and the lateral malleolus, and PAL was performed on the medial side of the lower leg. The lymphatic vessel depth was measured from the ankle joint, 10 cm above the medial malleolus, and 20 cm above the medial malleolus on PAL in the cross-sectional view and was compared between the participant groups. RESULTS: The healthy group (mean age, 43.3 ± 12.9 years) included 21 limbs of 4 male and 16 female healthy individuals (bilateral limbs of 1 patient were considered). The lymphedema group (mean age, 62.0 ± 11.7 years) included 17 limbs of 3 male and 14 female patients with lymphedema. The average lymphatic vessel depths from the ankle joint, 10 cm above the medial malleolus, and 20 cm above the medial malleolus were 2.6, 4.7, and 5.6 mm in the healthy group and 3.6, 7.3, and 7.4 mm in the lymphedema group, respectively. Lymphatic vessels were significantly deeper in the lymphedema group than in the healthy group at all measurement locations. CONCLUSIONS: Using PAL, we determined the lymphatic vessel depth in living bodies. By searching for the lymphatic vessels based on our findings, even surgeons who are relatively inexperienced with lymphatic surgery may be able to identify functional lymphatic vessels more efficiently.

A Patient With Cryptotia Corrected With Intraoperative Tissue Expansion and Superior Auricular Muscle Transfer Through a Small Hairline Incision.

Cryptotia is a relatively common auricular congenital anomaly in Asia. Nonsurgical molding is easy in infancy. However, surgical correction is often necessary after infancy. The authors report a case of cryptotia in which intraoperative tissue expansion and superior auricular muscle transfer were performed through a small incision at the hairline with good results. The patient is a 7-year-old girl. Three years after the operation, successful results were obtained. This method is advantageous as the procedure is simple, risk of relapse can be reduced by also treating the auricular muscle, and scarring is relatively inconspicuous. In addition, it is possible to switch to another technique when the improvement is poor.

Maxillary Reconstruction With a Rib-attached Free Latissimus Dorsi Muscle Flap.

In defect reconstruction after maxillary tumor resection, filling the dead space created by resection and reconstruction of surrounding areas are crucial for good cosmetic outcomes. Although various procedures have been described in the literature, most are complex and require advanced surgical skills. Therefore, in this study, the authors aimed to identify a simple procedure for successful reconstruction with minimal bone fixation. Three patients who underwent total maxillectomy and reconstruction using the rib-attached free latissimus dorsi flap at Keio University Hospital between 2012 and 2014 were included and followed up with for a minimum of 5 years. After total maxillectomy, the authors used a free latissimus dorsi flap with a portion of the rib to fill the dead space and reconstructed the orbit, nasal cavity, and oral cavity.The authors performed a rigid reconstruction of the zygomatic ridge using only 2-point plate fixations of the ribs at the outer orbit and anterior nasal spine. Patients were followed up for ≥5 years, and the flap successfully survived in all cases. There was an issue with rib fixation in 1 case; however, all patients were highly satisfied with the procedure's cosmetic results.

Influence of the Number of Revision Surgeries and Nasal Symmetry After Final Rhinoplasty for Patients With Cleft Lip.

The effects of operative intervention on vertical nasal growth in patients with unilateral cleft lips (CLs) are well described. However, the factors influencing nasal symmetry have not been sufficiently evaluated. Therefore, this study aimed to study the factors that cause difficulties in obtaining nasal symmetry postoperatively in patients with CLs. We conducted a retrospective analysis using data from patients with CLs who underwent a series of treatments at Keio University Hospital from 1990 to 2000. We collected data on the patients' sex, cleft type, number and time of revision surgery, palatal fistula incidence, and history of the pharyngeal flap and orthognathic surgery. Nasal symmetry was analyzed as the symmetrical ratio after the final touch-up surgery, and multivariate analysis was conducted using binary logistic regression to determine the factors affecting nasal symmetry. This study included 89 patients with unilateral CL. Multivariate analysis revealed that complete cleft lip and palate ( P < 0.05, odds ratio = 4.37) and repeated revision surgery ( P < 0.05, odds ratio = 9.28) were significant predictors of the final nasal symmetry. Our study showed that cleft type and the number of revision surgeries were identified as important factors for obtaining nasal symmetry after final touch-up rhinoplasty. Revision surgery may be necessary to relieve patients' psychological stress due to nasal deformity, suggesting that this dilemma needs to be overcome.

Incidence of Otalgia After Orthognathic Surgery.

BACKGROUND: In orthognathic surgery, it is well known that maxillary osteotomies and displacements sometimes affect auditory function. Thus, this study examined the relationship between the direction of maxillary displacement and postoperative otalgia. METHODS: Twenty consecutive patients underwent Le Fort I maxillary osteotomy using advancement, impaction, setback, or a combination of these procedures. The direction of movement and incidence of otalgia were investigated. Patients provided informed consent preoperatively, and postoperative reassurance was prudent. RESULTS: Pure-tone average evaluation based on horizontal or vertical movements did not show significant differences, although vertical movements resulted in fewer changes in the hearing threshold. Specifically, no significant changes were observed in the hearing thresholds of patients after surgery. No significant difference was also observed between horizontal and vertical movements in the tympanometry results. Negative changes were found in the results of the Eustachian tube dysfunction test in vertical movements, which returned to preoperative values in the final test. CONCLUSIONS: The risk of minor changes in hearing function is probable during the first week after orthognathic surgery; however, these negative changes either completely disappear or remain negligible.

Influence of Lip Revision Surgery on Facial Growth in Patients With A Cleft Lip.

Although patients with cleft lip and palate often present with poor maxillary growth because of intrinsic and iatrogenic factors, the surgical influence of lip revision surgery, palatal fistula repair, and pharyngeal flap procedures remains uncertain in contrast to that of primary cleft lip repair and palatoplasty. Therefore, this study aimed to reveal factors inhibiting maxillary growth and inducing later orthognathic surgery. A retrospective analysis was conducted on the data of patients with cleft lip and palate who underwent a series of treatments at Keio University Hospital from 1990 to 2000. We collected data on patient sex, cleft type, number and timing of lip revision surgery, the incidence of palatal fistulae, history of pharyngeal flap procedures, and timing of a repeat bone graft, and reviewed whether these patients underwent orthognathic surgery later in life. Multivariate analysis was conducted using binary logistic regression to extract factors affecting later orthognathic surgery. A total of 52 patients were included in this study. Results showed that revision surgery conducted more than twice was the highest statistically significant predictor of later orthognathic surgery in patients with a cleft lip and palate ( P <0.05, odds ratio=43.3), followed by palatal fistula occurrence after cleft palate repair ( P <0.05, odds ratio=22.3). Therefore, primary surgical procedure is most important for these patients.

New Senolysis Approach via Antibody-Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin Rejuvenation.

Senescent cells accumulate in aging skin, causing age-related changes and a decline in functional efficiency. Therefore, senolysis, a treatment that specifically removes senescent cells and rejuvenates the skin, should be explored. We targeted apolipoprotein D (ApoD), a previously identified marker expressed on senescent dermal fibroblasts, and investigated a novel senolysis approach using a monoclonal antibody against this antigen and a secondary antibody conjugated with the cytotoxic drug pyrrolobenzodiazepine. Observations using fluorescently labeled antibodies revealed that ApoD functions as a surface marker of senescent cells and that the antibody is taken up and internalized only by such cells. The concurrent administration of the antibody with the PBD-conjugated secondary antibody specifically eliminated only senescent cells without harming young cells. The antibody-drug conjugate treatment of aging mice combined with the administration of antibodies reduced the number of senescent cells in the dermis of mice and improved the senescent skin phenotype. These results provide a proof-of-principle evaluation of a novel approach to specifically eliminate senescent cells using antibody-drug conjugates against senescent cell marker proteins. This approach is a potential candidate for clinical applications to treat pathological skin aging and related diseases via the removal of senescent cells.

Cistanche deserticola Polysaccharide Reduces Inflammation and Aging Phenotypes in the Dermal Fibroblasts through the Activation of the NRF2/HO-1 Pathway.

Dermal fibroblasts maintain the skin homeostasis by interacting with the epidermis and extracellular matrix. Their senescence contributes to functional defects in the skin related to aging. Therefore, there is an urgent need for novel therapeutic agents that could inhibit fibroblast senescence. In this study, we investigated the effects of Cistanche deserticola polysaccharide (CDP), a natural anti-inflammatory component, on the progression of senescence in human dermal fibroblasts. Normal human dermal fibroblasts (NHDFs) were cultured in passages, and highly senescent cells were selected as senescent cells. CDP treatment increased the cell proliferation in senescent NHDFs and decreased the proportion of senescence-associated-ß-galactosidase-positive cells. The treatment suppressed the senescence-related secretory phenotype, and reactive oxygen species (ROS) production was reduced, alleviating H2O2-induced oxidative stress. CDP mitigated ROS formation via the nuclear factor erythroid 2-related factor/heme oxygenase-1 pathway in senescent cells and was involved in the suppression of upstream p-extracellular signal-regulated kinase. These results indicate that CDP is an antioxidant that can alleviate age-related inflammation and may be a useful compound for skin anti-aging.

Iatrogenic Cushing syndrome due to topical corticosteroids after skin graft surgery for giant nevus: A case report.

Iatrogenic Cushing syndrome (ICS) may be caused by exposure to corticosteroid therapy. We report a case of ICS caused by topical corticosteroids applied to the skin after skin graft surgery. We presume that the development of ICS, in this case, was attributed to a combination of skin barrier disruption, usage of high-potency corticosteroids, broad application area/ large quantity of the corticosteroid, and the extended treatment period. Patients may be at risk for ICS after extensive skin graft surgery if large amounts of very potent topical corticosteroids are applied for an extended period to prevent scar formation or relieve itching.

In Vivo Label-Free Observation of Tumor-Related Blood Vessels in Small Animals Using a Newly Designed Photoacoustic 3D Imaging System.

Photoacoustic (PA) technology can be used for non-invasive imaging of blood vessels. In this paper, we report on our prototype PA imaging system with a newly designed ultrasound sensor and its visualization performance of microvascular in animal. We fabricated an experimental system for animals using a high-frequency sensor. The system has two modes: still image mode by wide scanning and moving image mode by small rotation of sensor array. Optical test target, euthanized mice and rats, and live mice were used as objects. The results of optical test target showed that the spatial resolution was about two times higher than that of our conventional prototype. The image performance in vivo was evaluated in euthanized healthy mice and rats, allowing visualization of detailed blood vessels in the liver and kidneys. In tumor-bearing mice, different results of vascular induction were shown depending on the type of tumor and the method of transplantation. By utilizing the video imaging function, we were able to observe the movement of blood vessels around the tumor. We have demonstrated the feasibility of the system as a less invasive animal experimental device, as it can acquire vascular images in animals in a non-contrast and non-invasive manner.

An Elderly Patient With Crouzon Syndrome Treated With Monobloc Distraction.

Monobloc advancement by distraction osteogenesis is the treatment of choice in patients with syndromic craniosynostosis. This procedure is usually performed at 18 to 24 months/5 to 10 years of age. Herein, we present the case of a male patient with Crouzon syndrome who underwent monobloc advancement at the age of 62 years. Although the patient lived a normal life (employed, married, and being a father of a daughter), he visited our hospital for surgical improvement in facial esthetics. The patient underwent monobloc advancement by distraction osteogenesis. He was satisfied with the postoperative esthetic improvement and did not experience any major complications. This case highlights the fact that patients with syndromic craniosynostosis desire esthetic improvement and suggests that multidisciplinary treatment involving both the neuro and plastic surgeons is important in such cases.

Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3.

The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. Thus, senolysis, a therapy aimed at rejuvenation by removing senescent cells from the body, is being developed. However, this therapy requires the identification of membrane surface antigens that are specifically expressed on senescent cells for their selective elimination. We showed that atypical chemokine receptor 3 (ACKR3), a receptor of the CXC motif chemokine 12 (CXCL12) implicated in cancer, inflammation, and cardiovascular disorders, is selectively expressed on the surface of senescent human fibroblasts but not on proliferating cells. Importantly, the differential presence of ACKR3 enabled the isolation of senescent cells by flow cytometry using anti-ACKR3 antibodies. Furthermore, antibody-dependent cellular cytotoxicity assays revealed that cell surface ACKR3 preferentially sensitizes senescent but not dividing fibroblasts to cell injury by natural killer cells. Conclusively, the selective expression of ACKR3 on the surface of senescent cells allows the preferential elimination of senescent cells. These results might contribute to the future development of novel senolysis approaches.

Fibroblast Growth Factor 7 Suppresses Fibrosis and Promotes Epithelialization during Wound Healing in Mouse Fetuses.

Adult mammalian wounds leave visible scars, whereas skin wounds in developing mouse fetuses are scarless until a certain point in development when complete regeneration occurs, including the structure of the dermis and skin appendages. Analysis of the molecular mechanisms at this transition will provide clues for achieving scarless wound healing. The fibroblast growth factor (FGF) family is a key regulator of inflammation and fibrosis during wound healing. We aimed to determine the expression and role of FGF family members in fetal wound healing. ICR mouse fetuses were surgically wounded at embryonic day 13 (E13), E15, and E17. Expression of FGF family members and FGF receptor (FGFR) in tissue samples from these fetuses was evaluated using in situ hybridization and reverse transcription-quantitative polymerase chain reaction. Fgfr1 was downregulated in E15 and E17 wounds, and its ligand Fgf7 was upregulated in E13 and downregulated in E15 and E17. Recombinant FGF7 administration in E15 wounds suppressed fibrosis and promoted epithelialization at the wound site. Therefore, the expression level of Fgf7 may correlate with scar formation in late mouse embryos, and external administration of FGF7 may represent a therapeutic option to suppress fibrosis and reduce scarring.