Therapeutic Benefits of Stem Cells and Exosomes for Sulfur-Mustard-Induced Tissue Damage.

Sulfur mustard (SM) is a highly toxic chemical agent that causes severe tissue damage, particularly to the eyes, lungs, and skin. Despite advances in treatment, there is a need for more effective therapies for SM-induced tissue injury. Stem cell and exosome therapies are emerging as promising approaches for tissue repair and regeneration. Stem cells can differentiate into multiple cell types and promote tissue regeneration, while exosomes are small vesicles that can deliver therapeutic cargo to target cells. Several preclinical studies demonstrated the potential of stem cell, exosome, or combination therapy for various tissue injury, showing improvements in tissue repairing, inflammation, and fibrosis. However, there are also challenges associated with these therapies, such as the requirement for standardized methods for exosome isolation and characterization, the long-term safety and efficacy and reduced SM-induced tissue injury of these therapies. Stem cell or exosome therapy was used for SM-induced eye and lung injury. Despite the limited data on the use for SM-induced skin injury, this therapy is a promising area of research and may offer new treatment options in the future. In this review, we focused on optimizing these therapies, evaluating their safety and efficacy, and comparing their efficacy to other emerging therapeutic approaches potentially for SM-induced tissue injury in the eye, lung, and skin.

Spatiotemporal expression of NRAS and occurrence of giant congenital melanocytic nevi.

The mechanism underlying giant congenital melanocytic nevus (GCMN) formation is not fully understood. According to recent research, NRAS gene mutation is the main driving factor in GCMN. Melanocytic precursor cells proliferate during the embryonic stage after acquiring NRAS mutations. However, why GCMN undergoes intense proliferation in the embryonic stage and then stops postnatally remains unknown. The current theory for this phenomenon is that the GCMN undergoes oncogene-induced senescence. However, there is not enough evidence to indicate that senescence induces growth arrest in GCMN. In this study, we hypothesized that the expression level of the NRAS gene changes dynamically during the development and differentiation of neural crest cells into melanocytes and that the NRAS expression level determines whether the cell proliferates or becomes quiescent.

Antecubital Fossa Perforator Flaps for Soft-Tissue Defect Repair of the Anterior Elbow: Anatomical Study and Clinical Application.

BACKGROUND: The antecubital fossa is a main perforator cluster region located beside the anterior elbow defect, rendering it crucial to harvest the perforator pedicled flaps for the anterior elbow defects. PATIENTS AND METHODS: A total of 30 preserved cadaveric forearms were dissected in order to describe the perforator anatomy in the antecubital fossa. For each perforator, the number, the site of origin, the diameter at its origin, and the trajectory were recorded. In addition, all the patients treated for anterior elbow defects using inferior cubital artery (ICA) perforator pedicled flaps between June 2013 and June 2018 were reviewed in this retrospective study. RESULTS: A total of 85 perforators were dissected in the antecubital fossa area from the 30 specimens. Among these, 65 perforators originated from the radial artery, 6 from the recurrent radial artery, 13 from the brachial artery, and 1 from the ulnar artery. Each forearm specimen had a constant and large ICA perforator. All perforators originated from source vessels 2-5 cm distal from the interepicondylar line and could be harvested as perforator pedicled flap for anterior elbow reconstruction. In the clinical study, 11 patients with anterior elbow defects were treated with ICA perforator pedicled flaps with satisfactory functional and aesthetic outcomes. CONCLUSION: The antecubital fossa has a constant and dominant ICA perforator and many other perforators. The pedicled antecubital fossa perforator flaps could be harvested flexibly with a reliable blood supply for anterior elbow reconstruction.

Postburn Neck Reconstruction With Preexpanded Upper Back Perforator Flaps: Free-Style Design and An Update of Treatment Strategies.

BACKGROUND: For extensive postburn neck deformities, the preexpanded flaps in the upper back region were used and gained a uniform skin appearance and esthetic contours. Free-style perforator-based free-tissue transfer that represents the most recent advance in reconstructive surgery may provide more versatility of these flaps. METHODS: We retrospectively reviewed 31 patients treated at our institution for postburn neck contracture from March 2010 to May 2016. Various upper back flaps were designed according to the dominant perforators and the shape of the defect after fully releasing the neck contracture. RESULTS: Thirty-one patients received neck reconstructions with the versatile applications of the preexpanded upper back perforator flaps. Tip necrosis was observed in one case, and the others survived completely. The donor sites were all primarily closed. No incision dehiscence was observed. CONCLUSION: The free-style design has significantly increased the potential and versatility of the upper back flaps in reconstruction of severe neck scar contracture.

Application of Tissue Expansion with Perforator Flaps for Reconstruction of Challenging Skin Lesions.

BACKGROUND: One set of perforators can supply its own perforasome as well as the adjacent perforasome. The process of tissue expansion can mimic the effect of surgical delay to include more perforasomes into the perforator flap. By combining the perforasome theory with the technique of tissue expansion, large and various expanded perforator flaps can be achieved. METHODS: From July 2007 to July 2014, we performed eight different types of expanded perforator flaps in a total of 83 cases: 41 supraclavicular artery perforator flaps, 11 superficial cervical artery perforator flaps, 15 lateral thoracic perforator flaps, 6 internal mammary artery perforator flaps, 6 thoracoabdominal perforator flaps, 2 facial artery perforator flaps, 1 posterior interosseous perforator flap, and 1 ulnar collateral artery perforator flap. During the follow-up period, the survival rate, color, texture, and retraction of the flaps were assessed. RESULTS: The dimensions of the flaps ranged from 8 × 6 to 25 × 25 cm. Minor flap necrosis occurred in 20.5% of the cases, and severe flap necrosis developed in 2.4% of the cases. The donor sites were closed primarily in all but three cases. During the follow-up period (average, 13 months; range, 8-18 months), no flap contracture was observed with a good color and texture match. CONCLUSION: By combining the concept of perforasome with the technique of tissue expansion, flaps with large dimensions and reliable blood supply can be achieved, allowing a more flexible design to reconstruct various and challenging skin lesions.

Postburn Neck Contracture: Principles of Reconstruction and a Treatment Algorithm.

BACKGROUND: Various techniques have been developed for postburn neck reconstruction, but a treatment algorithm is needed. METHODS: We retrospectively reviewed all patients treated for postburn neck contracture at our institution between February 2008 and December 2015. Necks were divided into one anterior subunit and two lateral subunits marked by the sternocleidomastoid muscle. Deformities were categorized into three types according to their size and location. Type I deformities involve less than one subunit, type II deformities involve at least one subunit but less than two subunits, and type III deformities affect two or more subunits. Type II deformities were further divided into type IIa deformities, which mainly involve the anterior region, and type IIb deformities, which mainly involve the lateral region. RESULTS: Local random pattern flaps were constructed for type I deformities. Pedicled flaps from the anterior chest and supraclavicular areas were preferred for type IIa deformities, and pedicled flaps from the back were preferred for type IIb deformities. Pedicled flaps from other areas were the second choice for type II deformities, followed by free and prefabricated flaps. For type III deformities, bipedicled flaps were usually required. At a follow-up of at least 12 months, all patients showed near-normal neck function, and aesthetic features were significantly improved. CONCLUSION: The proposed classification and treatment algorithm for postburn neck reconstruction may help achieve satisfactory outcomes.

A Novel Technique for Reduction Malarplasty by Inward Displacement of Infractured Zygomatic Arch Without Fixation.

PURPOSE: Reduction malarplasty is one of the most common esthetic surgical procedures performed in the Asian population. Traditional procedures have several complications, such as bone nonunion, malunion, cheek drooping, and damage to the infraorbital nerve and maxillary sinus. Therefore, a more straightforward and effective method of reducing the width of the midface is needed. In this study, we introduce an infracture technique using inward displacement of the zygomatic arch without fixation. PATIENTS AND METHODS: A total of 680 patients received zygoma reduction using our method from 2012 to 2016 in the Department of Plastic Surgery, Minhang Shanghai Hospital. Radiologic and photographic documentation was completed preoperatively. The mean follow-up period was 24 months. The preoperative and postoperative photographs were compared. RESULTS: All patients were satisfied with their results. The mean operation time was approximately 35 minutes. The patients were discharged 5 days after the surgical procedure, and the mean recovery time was 2 weeks. The continuity of the outer cortex of the zygomatic complex and excellent bone union were observed in all patients 6 months postoperatively. The malar prominence underwent relapse in 23 patients and was reset. CONCLUSIONS: The new method that we developed has been proved safe and effective. It has 3 advantages. First, cheek drooping is avoided, and the damage caused by periosteum dissection on the whole zygomaticomaxillary area is limited. Second, bony fixation is unnecessary; thus the risk of bone nonunion, malunion, and a step-off deformity caused by improper fixation or looseness is prevented. Third, the operation time and the recovery time are short.

"Stamp Perforation" Technique for Correction of Prominent Mandibular Angle: 10 Years of Experience in Mandibular Reshaping in Asians.

Resection of a prominent mandibular angle is commonly used in Eastern society to improve the lower one third facial proportion. Historically, this procedure had a high complication rate, such as severe bleeding, asymmetry of the angle reduction, and "second mandibular angle." A safer and more effective way of performing such procedures is needed. The aim of this study is to introduce 3 instruments, a tunable guide handpiece, milling cutter, and flywheel, which were invented by the author, as well as a related ostectomy technique for correcting prominent mandibular angles using a modified full-thickness marginal ostectomy of the mandibular corpus angle, named the "stamp perforation" technique. This technique has 4 highlights: First, it ensures a smooth symmetric contour. Second, it prevents the risks of rupture of the inferior alveolar vessel and facial artery, ensuring the safety of this approach. Third, the "stamp perforation" technique eases the removal of bone fragments, shortening the operation time. Fourth, the recovery time of patients treated with this approach is much shorter than with the traditional approaches. From January 2006 to January 2016, 1106 patients underwent the surgery to contour the prominent mandible angles, and satisfactory results were achieved. Thus, we recommend the instruments as well as the "stamp perforation" technique for correcting prominent mandibular angles, and we hope that our 10 years of experience could provide a reference for other plastic surgeons.

An Anatomical Murine Model of Heterotopic Periorbital Subunit Transplantation.

BACKGROUND: Conventional reconstructive methods fail to achieve satisfactory results in total eyelid defect cases. Vascularized composite tissue allotransplantation might provide both good appearance and function for these patients. The structure of the eyelid is exceptional because it simultaneously consists of skin, connective tissue, the striated muscle, fiber structure, aponeuroses, and mucosa. Thus, before clinical application of eyelid allotransplantation, more experiments are needed to clarify the impact of ischemia, immunal suppressive agents, and deinnervation effects on these sophisticated structures. We developed an heterotopic periorbital transplantation model in rats to facilitate further experiment in this field. METHODS: Twenty-five inbred male Lewis rats were used for anatomy study (n=10), and as donors or recipients of the operations (n=10). In the anatomy study, the vascular distribution and innervation to the periorbital unit was identified and recorded. Then, according to the anatomy study, 10 heterotopic transplantations and 2 transplantations with pedicle ligated were performed. The posterior facial vein and the external carotid artery are selected as the graft pedicle. All transplanted eyelids were assessed daily. Micro-CT scanning and hematoxylin and eosin staining of the grafts were performed 60 days after the operation. RESULTS: All recipients tolerated the operation well. All grafts without pedicles ligated survived and new hair growth was observed. All of the transplanted eyelids were pink and pliable during the entire observation period, and we did not observe any signs of arterial or venous occlusion. In the recipients with graft pedicle ligated, the grafts were necrosed and mummified within 4 to 5 days. MicroCT of the survived grafts showed good blood supply and histologic staining revealed normal histologic morphologies. CONCLUSIONS: Our study proved the anatomical feasibility of periorbital transplantation by establishing a heterotopic transplantation model, which might facilitate future eyelid allotransplantation-related experiments.

Orthotopic forelimb allotransplantation in the rat model.

In this report, we present a rat orthotopic forelimb allotransplantation model. Eight forelimbs were transplanted from Brown Norway rats to Lewis rats. Axillary vessels of transplant were used as the vascular pedicles, which were anastomosed to the external jugular vein and common carotid artery of the recipient rat. The ulnar, radial, and median nerves were also repaired. Among rats, a tapered dose of cyclosporine was administered in five rats. In other three rats, no immunosuppressive therapy was given. The viability and signs of rejection of transplanted forelimbs, sensation recovery, bone healing, and histology were assessed up to the 90th postoperative day. All of rats but one survived surgery. All of transplanted forelimbs survived. In the rats treated with cyclosporine the transplanted forelimbs achieved long-term survival with motion and sensation recovery. On 90th day after surgery, bone healing was achieved. There was no sign of rejection in histology. In the rats without cyclosporine treatment, the transplanted forelimbs experienced tissue necrosis started from day 12 postoperatively. This experimental study showed the feasibility of orthotopic forelimb allotransplantation in the rat model. © 2015 Wiley Periodicals, Inc. Microsurgery 36:672-675, 2016.

Reconstruction of Postburn Full Facial Deformities With an Integrated Method.

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 × 18-32 × 30 cm) 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.

Rat model of heterotopic toe allotransplantation.

BACKGROUND: Finger allotransplantation is a promising treatment for severe finger destruction. However, more research is required to decrease the risks of this procedure to a level at which the clinical use of this non-life-saving procedure is justified. A proper animal model is essential for the required experiments. METHODS: In this article, we established a toe transplantation model based on anatomic studies. A tapered dose of Cyclosporine A (CsA) was used as an immunosuppressive therapy in the Brown Norway-to-Lewis allotransplantation experimental group, whereas isotransplantation or allotransplantation without treatment or with ligated pedicles was performed on the control groups. Recipients were assessed daily after operation for any signs of rejection and complications. On postoperative day 90, skin graft test was used to test the level of donor-specific tolerance in the recipients. On postoperative day 120, x-rays and micro-computed tomographies were performed for bone morphology evaluation. The chimerism in the recipient peripheral blood, lymph node, spleen, and thymus was tested by flow cytometry and immunohistochemical staining. And histologic study of the toe grafts and skin grafts were carried out. RESULTS: The blood supply of the toe graft was confirmed, and accordingly, transplantations were performed. The isografts survived indefinitely. The allografts with ligated pedicles experienced necrosis within 5 d. The allografts without treatment exhibited necrosis within 14 d. Forty percent, 20%, and 40% of the allografts associated with the CsA treatment experienced severe rejection, mild rejection, and nonrejection, according to gross graft appearance, respectively. Skin grafting tests showed three different types of results. X-rays and micro-computed tomographies reveal nearly normal bone morphologies in the bone structures of all surviving animals with grafts. Low levels of donor-specific chimerism were detected in the peripheral blood samples. Spleen, lymph node, and thymus chimerism were also confirmed in the long-term surviving animals with allografts. Histologic evaluation of the long-term survivals revealed similar graft morphologies in the isografts and the nonrejected allografts, inflammatory cell infiltration in the mildly rejected allografts, and degraded cutaneous appendages in the severely rejected allografts. CONCLUSIONS: We established a toe allotransplantation model. Moreover, the low rate of chimerism did not introduce specific tolerance, which might explain the high rejection rate. This model might facilitate future research in finger allotransplantation.

Desferrioxamine: a practical method for improving neovascularization of prefabricated flaps.

BACKGROUND: Prefabricated flaps are an ideal alternative to repair massive and complex tissue defects. Nevertheless, the risk of necrosis due to unpredictable blood supplies is a major obstacle to the application of prefabricated flaps. The survival of a prefabricated flap depends on the neovascularization between the vascular carrier and the donor tissue. Here, we proposed that the iron chelator, desferrioxamine (DFX), owned therapeutic effects that promoted the neovascularization of prefabricated flaps. METHODS: An abdominal prefabricated flap model was created in rats via a 2-stage operation. The rats were allocated into 4 groups as follows: 2 groups of rats received DFX treatments during the first or the second stage of the operation, respectively; 1 group of rats received a delay procedure 1 week before the second operation; and the final group was used as a blank control. Flap survival rates and capillary densities were evaluated between groups. The influence of DFX on the dermal fibroblasts was also studied in vitro. RESULTS: Desferrioxamine treatment during the first stage of the operation greatly increased flap survival rate compared to the blank control. The results were similar to those produced by the delay treatment. The vessel count results were consistent with the flap survival rate findings. In vitro, DFX treatment up-regulated the expression levels of several angiogenic factors in the dermal fibroblasts. Nevertheless, DFX treatment during the second stage of the operation was therapeutically detrimental. CONCLUSIONS: The application of DFX around the time of vascular carrier implantation greatly promoted neovascularization of prefabricated flaps, but was therapeutically detrimental after the flaps had been elevated.

A vascularized elbow allotransplantation model in the rat.

BACKGROUND: The aim of this research was to develop a rat model for vascularized composite allotransplantation (VCA) of the elbow. METHODS: We developed an animal model for VCA of the elbow in rats. Microvascular VCA was performed in 9 rats across a major histocompatibility barrier. Three different immunosuppressive regimens were provided. Joint mobility and weight-bearing capability were assessed throughout 90 days of life. Pedicle patency, bone blood flow, and histologic analyses were performed. RESULTS: In the cyclosporine group, forelimb activity was recovered during the postoperative 90 days. The extremity that was operated on was used in daily activities. There was minimal motion or use of the limb in the cyclosporine taper and control groups. The vascular pedicles were patent at the time of death in the cyclosporine-treated group but not in the remaining groups. Micro-computed tomography scan performed 3 months after transplantation revealed union at the bone junctions, and the elbow joint appeared grossly normal on death in the cyclosporine treatment group only. Incomplete healing was observed in the other 2 groups, and the elbow joints were grossly destroyed. Histologic examination revealed normal cartilage and bone cells in the cyclosporine-treated group, whereas the nontreated groups demonstrated lymphocytic infiltration and loss of normal histologic features. Flow cytometry of blood samples obtained on days 14, 30, 60, and 90 showed no recipient cell chimerism in any of the groups. CONCLUSIONS: We developed an animal model for elbow VCA. Immunosuppressed animals regained nearly normal function of forelimbs and maintained grossly normal elbow cartilage. Without cyclosporine treatment, the elbow transplants were rejected.

Prevention of necrosis of adjacent expanded flaps by surgical delay.

Although expanded flaps have been shown to survive longer than unexpanded flaps, flap necrosis still occurs, particularly when a deep back cut has been made. Overcautious design can avoid necrosis but leads to inefficient usage of the expanded flap. In this study, we tested a surgical delay method to prevent partial necrosis and maximize the use of the expanded flap. Ten patients with 13 expanders were included in this series. The surgical delay was performed 2 weeks before the final flap transfer. The survival of the delayed flaps was compared with that in previous cases without surgical delay. All 13 expanded flaps exhibited complete survival, which was significantly better than the 27.5% partial flap necrosis observed in nondelayed cases. Surgical delay can decrease the risk of necrosis in an expanded flap caused by a back cut and can thus maximize flap use.

Perioperative risk factors for vascularized composite allotransplantation: a systematic review and proposal of identity-defining VCA.

Vascularized composite allotransplantation (VCA) is a new dimension in reconstructive surgery. Generally, these procedures are offered for quality of life and functional indications rather than life-saving indications. Controversy exists, therefore, over the indications and risk/benefit ratios of VCA. Transplantation failure is a basic measurable risk of VCA. In this report we attempt to analyze perioperative factors associated with failures. Such factors are generally independent of technical performance and can be assessed to better define regulations applied to VCA. Ninety-one VCA procedures were identified, and 18 (19.8%) of them failed. Significant (P < 0.05) failure rates were associated with idiosyncratic cases (100%), cases performed without psychological screening (56.3%), cases performed without competent social support systems (44%), and cases done in developing countries (52.4%). A substantial but not significant failure rate was observed in cases performed without institutional review (36.4%). These findings suggest that institutional, professional, social, and ethical standards applied to VCA should require clarification of perioperative risk managements for any clinical VCA program, because such managements can be critical factors in determining outcome. The special character of these transplantation procedures suggest the concept of identity-defining vascularized composite allotransplantation (IVCA), for which psychological screening and third-party supervision is recommended.

Resurfacing severe facial burn scars: an algorithm based on three different types of prefabricated expanded flaps.

BACKGROUND: In the reconstruction of facial burn scars, large, thin, color-matching flaps are desirable due to aesthetic and functional demands. There have been many reports using prefabricated flaps to resurface facial skin lesions. However, an algorithm to select the most suitable treatment option for the individual patient is lacking. METHODS: An algorithm for facial resurfacing based on three types of prefabricated flaps from the cervical, periclavicular, and lateral thoracic area was setup, and 15 were patients treated accordingly. RESULTS: All 15 prefabricated flaps survived. Minor necrosis at the distal flap edge developed in three cases. After a follow-up of at least 6 months, all patients showed satisfactory aesthetic and functional outcomes. CONCLUSION: By individual selection of the most suitable option among these three types of prefabricated flaps, satisfactory resurfacing can be achieved for most facial burn scars.

Beyond waste: understanding urine's potential in precision medicine.

Urine-derived stem cells (USCs) are a promising source of stem cells for cell therapy, renal toxicity drug testing, and renal disease biomarker discovery. Patients' own USCs can be used for precision medicine. In this review we first describe the isolation and characterization of USCs. We then discuss preclinical studies investigating the use of USCs in cell therapy, exploring the utility of USCs and USC-derived induced pluripotent stem cells (u-iPSCs) in drug toxicity testing, and investigating the use of USCs as biomarkers for renal disease diagnosis. Finally, we discuss the challenges of using USCs in these applications and provide insights into future research directions. USCs are a promising tool for advancing renal therapy, drug testing, and biomarker discovery. Further research is needed to explore their potential.

Autologous Tissue Repair and Total Face Restoration.

Importance: Total face restoration remains a challenge in modern reconstructive surgery. After 17 years of experiments and preliminary clinical studies, a new concept of face prefabrication was developed for face restoration with autologous tissue. Objective: To evaluate the long-term results of face restoration with autologous tissue and report a finalized and standardized approach of face prefabrication. Design, Setting, and Participants: In this single-center long-term retrospective study, 32 patients who underwent total face restoration between 2005 and 2022 were reviewed. These patients underwent total facial reconstruction, which included flap prefabrication, 3-dimensional printing, tissue expansion, and flap transfer with aid of indocyanine green angiography (IGA). The flap first undergoes prefabrication by transferring vascularized fascia under the skin of the selected chest. A tissue expander is then placed under the fascia to create a large, thin, reliable skin flap after expansion. Once completed, the flap is transferred to the face during the second stage of the reconstruction. Intraoperative IGA is performed to guide the design of subsequent openings for facial fissures. Data were analyzed from July to September 2023. Main Outcomes and Measures: Flap healing, reconstructive outcome, and patient recovery were assessed during follow-up. Three questionnaires, including the 36-Item Short Form Health Survey (SF-36), Aesthetic and Functional Status Score of Facial Soft-Tissue Deformities/Defects, and the EuroQoL Health-Related Quality of Life (EQ-5D-5L), were used to evaluate the quality of life and satisfaction with facial aesthetic and functional status. Results: Of 24 included patients, 14 (58%) were male, and the mean (range) age was 32.9 (8-62) years. The mean (range) follow-up was 5.6 (2-12) years. All patients reported a significant improvement in quality of life (SF-36), especially in mean (SD) social functioning (preoperative score, 53.65 [34.51]; postoperative score, 80.73 [19.10]) and emotional stability (preoperative score, 56.67 [25.55]; postoperative score, 71.17 [18.51]). A total of 22 patients (92%) went back to work. Mean (SD) facial aesthetic status (preoperative score, 4.96 [3.26]; postoperative score, 11.52 [3.49]; P < .001) and functional status (preoperative score, 11.09 [3.51]; postoperative score, 15.78 [3.26]; P < .001) also improved. In addition, there was a significant increase in overall satisfaction and self-reported health status (preoperative score, 8.13 [1.52]; postoperative score, 3.58 [2.31]). Conclusions and Relevance: In this study, 5-year follow-up results suggested that this innovative approach to total face restoration offered a safe and valid option for indicated patients, with acceptable reconstructive and cosmetic outcomes.

Precision nephrotoxicity testing using 3D in vitro models.

Nephrotoxicity is a significant concern during the development of new drugs or when assessing the safety of chemicals in consumer products. Traditional methods for testing nephrotoxicity involve animal models or 2D in vitro cell cultures, the latter of which lack the complexity and functionality of the human kidney. 3D in vitro models are created by culturing human primary kidney cells derived from urine in a 3D microenvironment that mimics the fluid shear stresses of the kidney. Thus, 3D in vitro models provide more accurate and reliable predictions of human nephrotoxicity compared to existing 2D models. In this review, we focus on precision nephrotoxicity testing using 3D in vitro models with human autologous urine-derived kidney cells as a promising approach for evaluating drug safety.