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Background: Midface reconstruction is challenging because the structures and deformities involved are complicated. In this study, we present a strategy for integrally reconstructing nasal and midfa...

Tissue ischemia usually leads to necrosis and is a threatening condition associated with reconstructive surgery. Promoting the survival of ischemic tissue is critical for improving clinical outcomes. Although various solutions based on stem cells have been reported, there are still limitations to clinical translation. The aim of this study was to develop an effective method to promote the survival of ischemic tissue. Adipose-derived CD34 + and CD34- cells were obtained by magnetic bead sorting from the stromal vascular faction (SVF). Adipose-derived stem cells (ADSCs) were collected by subculture. The angiogenic capacities of CD34 + cells, CD34- cells and ADSCs were evaluated in vitro by comparing mRNA and protein expression. Random axial flaps in nude mice were used to evaluate the efficacy of these cells in protecting tissue from necrosis. The effect of these cells in preventing inflammation was also evaluated. Our data suggest that CD34 + cells expressed higher levels of angiogenetic factors and lower levels of inflammatory factors than the other cell types. More vessel branches were formed when human umbilical vein endothelial cells (HUVECs) were treated with conditioned medium from CD34 + cells than conditioned medium from the other cell types. Compared to ADSCs, CD34 + cells showed significantly higher efficacy in promoting tissue survival. More CD31 + cells and higher levels of angiogenic factors were observed in tissues from the CD34 + group than in those from the other groups. Lower levels of the proinflammatory factors TNF-α and IL-1b and higher levels of anti-inflammatory factors were found in the CD34 + group than in the other groups. Adipose-derived CD34 + cells showed better efficacy in improving ischemic tissue survival than ADSCs by reducing tissue inflammation and promoting angiogenesis. CD34 + cells can be obtained easily and may be suitable for clinical applications.

Background: Minoxidil (MXD) is an U.S. Food and Drug Administration-approved drug for the topical treatment of androgenetic alopecia (AGA) with minor side effects, but its hair growth (HG) effect is unsatisfactory. Methods: A double-blinded within-subjects randomized clinical trial was conducted on 16 male AGA patients who showed limited improvement after MXD treatment. Eligible participants received three concentrated growth factor (CGF) injections on half of the scalp and the placebo on the other side at 4-week intervals, and MXD was applied twice daily on both sides throughout the follow-up period. The primary endpoint was the HG ratio at V4. The secondary endpoints included the HG ratios at V2, V3, and V5; hair density and T/V ratio at V2, V3, V4, and V5; Global Aesthetic Improvement Scale (GAIS) scores at V4 and V5; and participant satisfaction at V4. Results: Each group included 16 subjects; each half of the scalp was randomly assigned to the MXD+CGF or MXD group. The HG ratio at V4 was higher in the MXD+CGF group than in the MXD group. The MXD+CGF group had significant improvements in hair density, HG ratio, and T/V ratio compared with the MXD group over the follow-up period. The GAIS scores and participant satisfaction were higher in the MXD+CGF group than in the MXD group. Unexpectedly, the MXD+CGF treatment hastened HG, which was sustained for 3 months after discontinuation. No severe adverse events occurred. Conclusions: The combined treatment of MXD and CGF is safe and more efficient for AGA patients. Combining CGF can expedite the potency of MXD and provide patients with fast and lasting HG.

Background The regeneration response of the skin to mechanical stretching in vivo has been explored in reconstructive surgery to repair large-scale deformities. The ability of the skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous stromal vascular fraction (SVF) cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration. Methods This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with exhausted regeneration. Twenty eligible participants received intradermal injections of the SVF or placebo treatments. Follow-ups were conducted at 4, 8, and 12 weeks to assess efficacy and at 2 years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included skin thickness at 4 and 8 weeks, the expansion index (EI), and the skin texture score at 12 weeks. Results The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI − 1.43 to − 0.11]; p = 0.018) and 12 weeks (0.65 [95% CI − 1.30 to − 0.01]; p = 0.046). In the SVF group, the increase in skin thickness was significant at 4 weeks (0.49 [95% CI − 0.80 to − 0.06]; p = 0.010) to 8 weeks (0.45 [95% CI − 0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI − 0.07 to 0.91]; p = 0.037). The SVF group showed greater EI increases than the control group (0.50 [95% CI − 0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were greater than those in the control group at 12 weeks. Histologically, SVF-treated expanded skin showed more proliferating cells and blood vessels, and the extracellular matrix volume increased. No severe adverse events occurred. Conclusions Transplantation of SVF cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue. Trial registration This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2000039317 (registered 23 October 2020—retrospectively registered).

Background In full-thickness nasal defects, the internal lining is perhaps the most challenging aspect of the three layers to rebuild. Nasal damage is usually more concentrated on the tip, soft triangles, alar wings, and columella, but the lateral nasal arteries are often left intact and the damage to the dorsal sidewalls are normally superficial. Methods Twelve patients who required total nasal reconstruction received a forehead flap placement as external coverage and autologous rib cartilage as structural support. Residual normal/superficial scar tissue flaps on the dorsal sidewalls with lateral nasal artery pedicles were mobilized and designed for internal lining repair without creating secondary donor site damage. The flaps were then turned 180° downward and placed between the alar medial angles and the fornix. Results No total lining flap necrosis occurred in all the patients. Partial necrosis occurred on the distal edge owing to overpressure of the nostril splint to the flaps; however, the wounds eventually healed, and the nasal structural integrity was preserved. The patients were satisfied with the aesthetic results and had no complaints of airway stenosis. Conclusions Lateral nasal artery pedicle dorsal sidewall skin flaps are appropriately thick, providing enough nostril circumferential support to improve airway stenosis. It allows sufficient blood supply and creates no extra donor site damage. Blood vessels and skin flaps are often undamaged, thereby allowing maximum application in total nasal reconstruction.

Background: The regeneration response of skin to mechanical stretching in vivo has been explored in reconstructive surgery for repairing large-scale deformities. The ability of skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous adipose-derived stem cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration.Methods: This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with a presence of exhausted regeneration. Twenty eligible participants received intradermal injections with stromal vascular fraction (SVF) or placebo treatments. Follow-ups were conducted at 4, 8, and 12-weeks to assess efficacy and for 2-years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included the skin thickness at 4 and 8 weeks, the expansion index (EI) and the skin texture score at all visits. Results: The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI -1.43 to -0.11]; p = 0.018) and 12 weeks(0.65 [95% CI -1.30 to -0.01]; p = 0.046). In the SVF group, the increment of skin thickness was significant at 4 weeks (0.49 [95% CI -0.80 to -0.06]; p = 0.010) to 8 weeks (0.45 [95% CI -0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI -0.07 to 0.91]; p = 0.037). The SVF group showed higher EI increments than the control group (0.50 [95% CI -0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were higher than those in the control group at 12 weeks. Histologically, the SVF-treated expanded skin showed more proliferating cells and blood vessels, and the volume of extracellular matrix increased. No severe adverse events occurred.Conclusions: Transplantation of autologous adipose-derived stem cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue. Trial registration: This trial was registered with Chinese Clinical Trial, ChiCTR2000039317 (registered 23 Oct 2020 - retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=62738).

BACKGROUND Current rodent models of wound healing and scarring are flawed because of rapid wound contraction and inconspicuous scarring after healing, which is not closely parallel to the physiologic process in humans. This study aimed to establish a novel model of wound healing and scarring in rats. METHODS Excisional wounds were generated in rat tail or dorsal skin and histologic changes and wound contraction were assessed 2, 10, and 16 days after injury. After healing, rat tail scar was investigated for 24 consecutive weeks by histologic and immunohistochemical staining. Finally, a stretched scar model was generated in rat tail with high or low strain after reepithelialization to mimic human hypertrophic scars. The tail hypertrophic scars were analyzed by histology, immunohistochemical staining, and mRNA quantification 0, 2, 6, 12, and 24 weeks after stretching. RESULTS Compared with the dorsal wounds, a larger dermal gap percentage (p < 0.05) and more pronounced granulation were found in rat tail wounds. Tail scars remained conspicuous and underwent maturation over 24 weeks after wound healing. In addition, high mechanical strain induced significantly increased scar area (p < 0.01), scar height (p < 0.05), vessel density (p < 0.01) and hypertrophic scar-related molecule expression, and distorted collagen arrangement in rat tail scars. CONCLUSIONS The rat tail model exhibits minor wound contraction and biological features analogous to both normotrophic and hypertrophic scar in humans when generated with or without stretching, respectively. It is a promising new model for studies of both cutaneous wound healing and scarring.

Background : Soft tissue expansion is a common technique for the regeneration of extra skin to repair skin defects. However some warning signs like skin thinning and telangiectasia are often found during the expansion process, which indicates the skin flaps cannot be further expanded. These signs may result in the suspension of expansion or ultimately jeopardize the final outcome. Fat grafting is used to treat these potential complications and enable continuation of the expansion procedure in some cases. In this study, we aimed to investigate the efficiency and safety of fat grafting in this process. Methods : The study was conducted on patients from January 2012 to December 2017 with warning signs of expansion treated with fat grafting (treatment group) or pause expansion (control group). Follow-up data, such as expansion status, dermal thickness, telangiectasia, skin texture using volume assessment, B-mode ultrasound, and semiquantitative scoring were collected. Results : A total of 67 expanded skin regions with warning signs were enrolled. The expansion fold increased 2.14-fold at 12 weeks after treatment compared with 0.74-fold in control (P=0.02).The semiquantitative score was significant improved at 4 weeks (9.03 ± 0.73 vs. 7.45 ± 0.55; p=0.033). Meanwhile, the skin thickness in the experimental group did not show decreasing trend even in the continued expansion process. Conclusions : Autologous fat grafting represents an effective and safe method to rescue expanded skin from limited skin regeneration. This technique also represents a valuable tool to increase the chances for further expansion. Key Words : Autologous fat grafting;Skin expansion; Skin regeneration

Background Mechanical stretch, in term of skin expansion, can induce effective but limited in vivo skin regeneration for complex skin defect reconstruction. We propose a strategy to obtain regenerated skin by combining autologous stem cell transplantation with mechanical stretch. Methods This randomized, blinded placebo-controlled trial enrolled 38 adult patients undergoing skin expansion presenting with signs of exhausted regenerative capacity. Patients randomly received autologous bone marrow mononuclear cell (MNC) or placebo injections intradermally. Follow-up examinations were at 4, 8 weeks and 2 years. The primary endpoint was the volume achieved in relation to the designed size of the expander (expansion index, EI). Secondary endpoints were surface area, thickness and texture of expanded skin. This trial is registered with ClinicalTrial.gov, NCT01209611. Findings The MNC group had a significantly higher EI at 4 weeks (mean difference 0.59 [95% CI, 0.03–1.16]; p = 0.039) and 8 weeks (1.05 [95% CI, 0.45–1.66]; p = 0.001) versus controls. At 8 weeks, the MNC group had significantly thicker skin (epidermis: p, Highlights • This study shows that intradermally transplanted MNCs in mechanical stretched skin is a safe and feasible clinical application. • Intradermally transplantation of MNCs can overcome the regenerative limitations of skin. • The strategy of combining stem cell and microenvironment can provide significant amounts tissue for surgical reconstruction. Though stem cells are proved to participate in tissue regeneration, there is seldom clinical research combining stem cell and in vivo mechanotransduction to provoke skin regeneration. In this study, we introduce autologous bone marrow stem cells to mechanical stretch induced skin regeneration. The results showed that the potential of autologous stem cells in promoting skin regeneration. The application of stem cell assisted skin expansion can overcome the regenerative limitations of skin to provide significant amounts tissue for surgical reconstruction. The integration of stem cells and mechanical stretch stimuli will engender further advances in in vivo tissue regeneration.

Background: The face is one of the most important regions of the human body and contains complicated and delicate features that define the identity of a person. Treatment for extensive facial deformities requires resurfacing of the extensive skin defects and restoring the missing features. To date, it remains a major challenge to the reconstructive surgeons. Methods: The authors reviewed their patients of Type III and Type IV facial deformities to introduce an integrated method for total facial reconstruction. The entire management included flap prefabrication, skin over-expansion, bone marrow mononuclear cell transplantation, and multistaged revisions to reshape the face contours. The treatment details and postoperative results were presented. Aesthetic and functional status scores were independently evaluated to analyze the effectiveness of this intervention. Results: Forty-two patients with severe facial deformities were included. In 2 patients of total face reconstruction, bone marrow mononuclear cell transplantation was conducted. Each patient had facial reconstruction with a prefabricated flap (range 23 x 18-32 x 30 cm(2)) that resurfaced the entire defect. Tip necrosis occurred in 2 patients. The aesthetic and functional status scores were statistically improved. Good skin compliance, normal contours, and emotional expression were noted. Conclusions: The integrated method is a reliable and excellent option for extensive facial deformities involving both central and peripheral facial units while avoiding multiflap reconstructions. It creates a desirable coverage with minimal scars, which are both important for a "perceived normal'' face.

Background Although various salvage methods have been proposed to treat intraretinal artery hyaluronic acid embolism, their applications are still limited by various factors. The authors investigated the effectiveness of intravenous hyaluronidase with urokinase for resolving retinal artery hyaluronic acid embolism. Methods The anatomy of rabbit ophthalmic and fundus arteries (retinal and choroid artery) was studied. Approximately 0.35 ml of hyaluronic acid was injected into the ophthalmic artery to create a retinal artery embolism model. The rabbits were grouped randomly (groups A, B, C, D, E, and F) and given hyaluronidase with urokinase intravenously at different postobstruction time points (10, 20, 30, 40, 50, and 60 minutes). Saline was given to the control group. Fundus vascular (retinal and choroid artery) reperfusion status and the effectiveness of the solution on the obstruction of each group were observed for 5 days. Results The animal model closely imitated actual hyaluronic acid ophthalmic/retinal artery obstructions. Three vascular conditions were observed after hyaluronidase with urokinase injection: total, partial, and no reperfusion. Groups A, B, and C showed a significantly higher overall solution effectiveness rate (total/partial reperfusion) compared with the control group (p = 0.001, p = 0.001, and p = 0.005, respectively). Solution effectiveness in groups D, E, and F showed no difference compared with the control group (p = 0.628, p = 1.000, and p = 1.000, respectively). The effectiveness of the solution drops dramatically if given after 30 minutes of obstruction. Conclusions The authors' method can indeed help resolve retinal artery hyaluronic acid obstruction. Intravenous hyaluronidase with urokinase technique shows possible potential to become a standardized treatment protocol for intraretinal artery hyaluronic acid embolism with further clinical tests.

Cross-linked hyaluronic acids (HAs) with varying characteristics and formulations are available. Despite the popularity of HA, limited studies compared the effectiveness of monophasic monodensified hyaluronic acid (MMHA) and biphasic nonanimal stabilized hyaluronic acid (BHA) products in correcting nasolabial folds (NLFs) in the Asian population.This double-blinded, randomized research aimed at evaluating the outcomes of MMHA and BHA products in treating Asian NLFs.Subjects aged between 18 and 65 years with moderate-to-severe NLFs were randomized to receive MMHA or BHA treatment. A touch-up treatment with the same product was performed at the 4-week follow-up, if needed. The effectiveness was evaluated for 24 weeks by masked investigators. All adverse events were recorded for safety evaluation.Twenty-five subjects in the MMHA Group and twenty-four subjects in the BHA Group finished 24-week follow-up. Results showed that subjects from both groups obtained satisfactory outcome in NLF correction. A lower amount of MMHA was required to achieve a similar result as that of BHA (p.01). Both HA products maintained the effectiveness at the end of the 24-week follow-up.Both MMHA and BHA are effective for correcting NLF in Asian patients, producing satisfactory results. Monophasic monodensified hyaluronic acid provides similar satisfaction to BHA while requiring less injection volume.

Background Supraclavicular flaps had been widely used as pedicled flaps to reconstruct face and neck defects. However, the size of this traditional flap was limited even after expansion. In this study, we present a flap pedicled by the thoracic branch of supraclavicular artery (TBSA). The flap is located at the subclavicular region, and has the advantage of large dimension, matching colour and thin thickness. Methods In this series, 24 patients with ages ranging between 3 and 49 years (30 flaps with six patients in bilateral fashion) were treated in the authors’ institution. Results The maximum size of the flap was 25 cm × 25 cm, whereas the minimum size was 15 cm × 10 cm. The average size of the flaps was 241.1 ± 95.7 cm2. Twenty-six flaps (86.7%) survived completely. Total flap loss was seen in one patient (3.3%) and was treated with reverse harvesting skin graft. Partial flap necrosis occurred in three flaps (10.0%). Through a mean time of 10-month follow-up, the colour and the texture of the flaps matched with the recipient area. No conspicuous flap contracture was observed. Conclusion This expanded subclavicular flap pedicled by the TBSA has proved to be a promising method with satisfactory outcome and high success rate.

Total face skin and soft-tissue defects remain one of the biggest challenges in reconstructive surgery. Reconstruction of the entire face with uniform coverage and delicate features is difficult to achieve. To avoid the patchwork result seen in multiple flaps and skin grafts, 1 monoblock flap that has similar color, texture, and thickness might be an ideal option to minimize the incisional scars and several surgical procedures but is unavailable with current approaches because of the lack of sufficient matched tissue and the unreliable blood supply for such a large flap. To acquire a monoblock flap for full face reconstruction, we combine the prefabricated flaps, skin overexpansion, and bone marrow mononuclear stem cell transplantation for total facial resurfacing. In this article, we present our experience from our case series that provides universally matched skin and near-normal facial contour. It is a reliable and an excellent reconstructive option for massive facial skin defect.