Delivery Strategies of Growth Factors in Cartilage Tissue Engineering.

Cartilage plays an important role in supporting soft tissues, reducing joint friction, and distributing pressure. However, its self-repair capacity is limited due to the lack of blood vessels, nerves, and lymphatic systems. Tissue engineering offers a potential solution to promote cartilage regeneration by combining scaffolds, seed cells, and growth factors. Among these, growth factors play a critical role in regulating cell proliferation, differentiation, and extracellular matrix remodeling. However, their instability, susceptibility to degradation, and potential side effects limit their effectiveness. This paper reviews the main growth factors used in cartilage tissue engineering and their delivery strategies, including affinity-based delivery, carrier-assisted delivery, stimulus-responsive delivery, spatial structure-based delivery, and cell system-based delivery. Each method shows unique advantages in enhancing the delivery efficiency and specificity of growth factors, but also faces challenges such as cost, biocompatibility, and safety. Future research needs to further optimize these strategies to achieve more efficient, safe, and economical delivery of growth factors, thereby advancing the clinical application of cartilage tissue engineering.

Poloxamer 188 washing of lipoaspirate improves fat graft survival: A comparative study in nude mice.

BACKGROUND: Autologous fat transplantation is limited by the uncertainty of graft retention, impeding its application. Among the current strategies for processing lipoaspirates, high-density fat (HDF) is recommended owing to the enrichment of stem cells and washing before cotton concentration for simplicity of operation. Poloxamer 188 (P188) washing has been shown to repair the membranes of damaged cells. This study aimed to investigate the effect of P188-washing on fat graft survival and identify the best technique for processing lipoaspirates. METHODS: Lipoaspirates were prepared using centrifugation to obtain HDF, which was then washed with saline or P188 followed by cotton concentration. Tissue integrity, adipocytic activity, and viability of stromal vascular fraction (SVF) in the samples from the 3 groups were assessed. Samples were sequenced in vitro using high-throughput RNA-seq, and differentially expressed genes were validated using qPCR and western blotting (WB). After transplantation under the dorsum of nude mice for 8 weeks, the grafts were extracted and examined for residual volume, histologic characteristics, and vascularization. RESULTS: The HDF and P188 groups showed a higher survival rate of SVF, more Ki67-positive cells, intact tissue structure, and lesser fibrosis than the saline group. There were no significant differences in the density of SVF and residual volume of grafts. HDF showed significantly improved vascularization during 8 weeks. Through RNA-seq and bioinformatic analysis, notable changes in several related genes after transplantation were observed. CONCLUSIONS: P188 treatment can prevent cells from apoptosis and preserve tissue viability, thereby improving graft quality. HDF contains large amounts of SVF and can be regarded as an excellent grafting material.

Double Reinforcing Strategy with Perpendicular Plate of Ethmoid in Asian Secondary Unilateral Cleft Rhinoplasty: A Finite Element Analysis.

BACKGROUND: Deviation and asymmetry relapse after secondary unilateral cleft rhinoplasty with septal extension graft is a common yet serious problem especially among Asian patients. Therefore, finding an effective approach to reduce deformity relapse remains a great challenge to plastic surgeons. METHODS: In this study, authors established finite element models to simulate different nasal cartilage-corrected options and different reinforcing strategies in secondary unilateral cleft rhinoplasty. A load of 0.01N was given to the nasal tip to simulate the soft tissue pressure, while two loads of 0.5N were separately given to the anterior and posterior part of the septal extension graft to simulate the rhinoplasty condition. Maximum deformations were evaluated to make stability judgments. RESULTS: The maximum deformation of different cartilage correction models in ascending order was: UCL deformity with septum correction, normal nasal cartilage, UCL nasal deformity, and UCL nasal deformity with lower lateral cartilage correction. When applied L-strut reinforcement graft was harvested from the perpendicular plate of the ethmoid bone, the maximum deformation of the models decreased significantly, and strong fixation of the septum could further enhance this decreasing effect. CONCLUSIONS: Correcting the septum and lower lateral cartilage together could improve the structural stability and symmetry in secondary unilateral cleft rhinoplasty. To keep the corrected septum stable and thus reduce deformity relapse, reinforcing the L-strut with perpendicular plate of ethmoid graft while strongly anchoring the septal cartilage to the anterior nasal spine was proved to be effective in both finite element analysis and clinical observation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Challenges in Application: Gelation Strategies of DAT-Based Hydrogel Scaffolds.

Decellularized adipose tissue (DAT) has great clinical applicability, owing to its abundant source material, natural extracellular matrix microenvironment, and nonimmunogenic attributes, rendering it a versatile resource in the realm of tissue engineering. However, practical implementations are confronted with multifarious limitations. Among these, the selection of an appropriate gelation strategy serves as the foundation for adapting to diverse clinical contexts. The cross-linking strategies under varying physical or chemical conditions exert profound influences on the ultimate morphology and therapeutic efficacy of DAT. This review sums up the processes of DAT decellularization and subsequent gelation, with a specific emphasis on the diverse gelation strategies employed in recent experimental applications of DAT. The review expounds upon methodologies, underlying principles, and clinical implications of different gelation strategies, aiming to offer insights and inspiration for the application of DAT in tissue engineering and advance research for tissue engineering scaffold development.

Snake-shaped ePTFE nasal tip graft combined with conchal cartilage in Asian rhinoplasty: a retrospective cohort study.

BACKGROUND: Lacking a nasal tip projection is a common deformity of Asian nasals. Various commonly used nasal tip grafts require dissecting septal perichondrium, most of them are autologous cartilage with a nonintegrated design. A snake-shaped expanded polytetrafluoroethylene (ePTFE) nasal tip graft is an integrated, stable tip graft without any additional assembly and splicing, conforming to the nasal anatomy characteristics of Asians. METHOD: A retrospective study was performed on Asian patients who underwent rhinoplasty in the nasal tip at Peking University Third Hospital from 2015 to 2022. Nasal tip grafts were categorized into three groups: snake-shaped ePTFE combined with conchal cartilage (n = 15), only costal cartilage (n = 25), and only conchal cartilage (n = 17). Patients were excluded if their rhinoplasty did not involve any of the grafts above. Visual Analogue Scale, FACE-Q Nose, FACE-Q Nostril, Nasal Obstruction Symptom Evaluation scale, and Rhinoplasty Outcome Evaluation scale were used to evaluate the preoperative and postoperative results. RESULTS: Fifty-three (93.0%) cases had low nasal dorsum and 46 (80.7%) cases had short nose. There was no significant difference in complication rates among the three groups. The difference between preoperative and postoperative scale scores was statistically significant among the three groups (p < 0.05). Score improvements, including all scales, were the highest in the costal cartilage group and lowest in the conchal cartilage group. CONCLUSIONS: Snake-shaped ePTFE nasal tip grafts can be an effective integrated alternative that provides long-term safety and efficacy compared with traditional autogenous implants (conchal and costal cartilages).

Construction Form and Application of Three-Dimensional Bioprinting Ink Containing Hydroxyapatite.

With the increasing prevalence of bone tissue diseases, three-dimensional (3D) bioprinting applied to bone tissue engineering for treatment has received a lot of interests in recent years. The research and popularization of 3D bioprinting in bone tissue engineering require bioinks with good performance, which is closely related to ideal material and appropriate construction form. Hydroxyapatite (HAp) is the inorganic component of natural bone and has been widely used in bone tissue engineering and other fields due to its good biological and physicochemical properties. Previous studies have prepared different bioinks containing HAp and evaluated their properties in various aspects. Most bioinks showed significant improvement in terms of rheology and biocompatibility; however, not all of them had sufficiently favorable mechanical properties and antimicrobial activity. The deficiencies in properties of bioink and 3D bioprinting technology limited the applications of bioinks containing HAp in clinical trials. This review article summarizes the construction forms of bioinks containing HAp and its modifications in previous studies, as well as the 3D bioprinting techniques adopted to print bioink containing HAp. In addition, this article summarizes the advantages and underlying mechanisms of bioink containing HAp, as well as its limitations, and suggests possible improvement to facilitate the development of bone tissue engineering bioinks containing HAp in the future.

Perfusable adipose decellularized extracellular matrix biological scaffold co-recellularized with adipose-derived stem cells and L6 promotes functional skeletal muscle regeneration following volumetric muscle loss.

Muscle tissue engineering is a promising therapeutic strategy for volumetric muscle loss (VML). Among them, decellularized extracellular matrix (dECM) biological scaffolds have shown certain effects in restoring muscle function. However, researchers have inconsistent or even contradictory results on whether dECM biological scaffolds can efficiently regenerate muscle fibers and restore muscle function. This suggests that therapeutic strategies based on dECM biological scaffolds need to be further optimized and developed. In this study, we used a recellularization method of perfusing adipose-derived stem cells (ASCs) and L6 into adipose dECM (adECM) through vascular pedicles. On one hand, this strategy ensures sufficient quantity and uniform distribution of seeded cells inside scaffold. On the other hand, auxiliary L6 cells addresses the issue of low myogenic differentiation efficiency of ASCs. Subsequently, the treatment of VML animal experiments showed that the combined recellularization strategy can improve muscle regeneration and angiogenesis than the single ASCs recellularization strategy, and the TA of former had greater muscle contraction strength. Further single-nucleus RNA sequencing (snRNA-seq) analysis found that L6 cells induced ASCs transform into a new subpopulation of cells highly expressing Mki67, CD34 and CDK1 genes, which had stronger ability of oriented myogenic differentiation. This study demonstrates that co-seeding ASCs and L6 cells through vascular pedicles is a promising recellularization strategy for adECM biological scaffolds, and the engineered muscle tissue constructed based on this has significant therapeutic effects on VML. Overall, this study provides a new paradigm for optimizing and developing dECM-based therapeutic strategies.

Repair of Asian nasal subunit defects using nasolabial perforator flaps: A retrospective study.

BACKGROUND: The application of nasolabial perforator flap for nasal reconstruction has been reported previously with satisfactory outcomes, but the outcomes and risk factors of postoperative adverse events have been unclear to plastic surgeons. AIMS: To statistically analyze the effectiveness of the nasolabial perforator flap in nasal reconstruction and the risk factor of postoperative complications and re-operation. PATIENTS/METHODS: This retrospective study evaluated 58 Chinese patients who underwent nasal reconstruction with the nasolabial perforator flap from 2009 to 2021. The esthetic and blood supply outcomes were measured by plastic surgeons on a 5-point Likert scale. Binary logistic regression was used to determine the risk factors associated with postoperative complications and re-operation. RESULTS: The mean age of the cohort was 66.4 ± 2.0 years. The defect size ranged from 6.5 × 5.5 mm2 to 40 × 70 mm2 , and 48.3% of defects covered more than one nasal subunit. Venous congestion occurred in 4.9% of flaps, and the immediate overall postoperative score was 7.72/10. More than one nasal subunit of involvement was the risk factor associated with re-operation (p = 0.004), but no risk factor was associated with complications. CONCLUSIONS: The nasolabial perforator flap is reliable for nasal reconstruction with good esthetic outcomes and fewer complications. However, a large number of involved subunits may lead to multiple surgeries for flap trimming in easterners.

Three-Dimensional Morphological Study on the Effectiveness of Expanded Polytetrafluoroethylene Prosthesis in the Paranasal Augmentation.

BACKGROUND: The paranasal depression is a common facial feature of Oriental populations. One of the most wildly used method to improve it was paranasal augmentation using expanded polytetrafluoroethylene (ePTFE). The effectiveness of it should be tested by three-dimensional morphological measurements. METHODS: Patients who underwent paranasal augmentation using ePTFE between January 2017 and December 2022 were recruited in the study. The preoperative and postoperative clinical variables and three-dimensional measurement of patients were also collected. The satisfaction outcome were assessed. RESULTS: By establishing a coordinate system based on the Frankfurt plane, 16 landmarks including nasal alar crest, subnasal point, upper lip, pogonion, glabella, sub-cheek, orbitale, tragion in left and right side of faces were marked. Five segments, 4 ratios, and 3 angles were measured based on it. The significant increase of segments, ratios, and angles indicated that paranasal augmentation could increase the protrusion of paranasal area, both in absolute value and relative proportion. The significant decrease of other data indicated that the protrusion difference between paranasal base and upper lip, forehead, and chin, respectively, were shortened after surgery. The average size of implant was 6.54 ± 1.02 mm, and the average increase of paranasal height was 4.38 ± 1.04 mm postoperatively. This indicates that two-thirds of its height will ultimately be reflected effectively in the sagittal elevation of the paranasal base. CONCLUSIONS: Paranasal augmentation using ePTFE could effectively increase paranasal height and improve subunits relationships, and the ePTFE prosthesis should be designed and carve considering the 1/3 loss of height after implantation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Morphological Measurement of Asian Osteal Nasal Base for Paranasal Augmentation.

BACKGROUND: Paranasal augmentation has been a popular approach in restoring Asian patients' lateral profile. Irregular surface in the surgical area emphasizes the importance of morphological evidence for the preoperative evaluation and the design of paranasal implants. METHODS: We retrospectively collected craniofacial computer tomography scans of patients in the department of plastic surgery from 2020 to 2022. The imaging data were imported to Mimics (version 20.0; Materialize, Leuven, Belgium) for three-dimensional reconstruction. Measurements of osteal nasal base were performed in 3-matics (version 12.0; Materialize). The severity of paranasal concavity was graded by a senior doctor to study the correlation with measured variables. RESULTS: Fifty-seven patients with a median age of 27 years (IQR: 22-33) were included in the study. For design of paranasal implants, the lengths of both lower and lateral edge were measured for reference. In the regression analysis, the alar base-alveolar process angle was significantly associated with the degrees of paranasal concavity (OR = 1.222, p = 0.00001). CONCLUSIONS: Morphological data of osteal nasal base were measured and presented in the current study. The analysis supported that alar base-alveolar process angle be used for preoperative grading and evaluation to help guiding treatment decisions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Morphological and Functional Effects of the Endoscope-Assisted One-Stage Approach for Crooked Nose.

BACKGROUND: A crooked nose is an external nose deformity predominantly caused by congenital aplasia or acquired secondary to trauma or surgery, often accompanied by a deviated nasal septum. Patients with crooked nose have dual needs to improve both esthetic and functional problems. METHODS: The clinical and photographic information of 48 patients diagnosed with a crooked nose and nasal septum deviation treated from January 2018 to January 2022 was acquired. The morphology and functional effects were investigated by evaluating the general condition of the operation, measuring the esthetic indexes of the nose, and subjectively scoring. RESULTS: For both morphology and function, endoscopy-assisted one-stage correction showed positive results in this study. The external nose deviation distance postoperatively measured 1.28 (0.85, 1.97) mm, which significantly decreased from the preoperative value of 3.96 (3.31, 5.29) mm. The scores of doctors and irrelevant medical students on nose morphology increased significantly from 4.75±1.88 and 3.84±0.76 to 6.48±1.21 and 7.21±0.67, respectively. The rhinoplasty outcome evaluation score and the "nasal obstruction symptom evaluation "score of patients were both significantly improved ( t = -7.508 and t =6.310, respectively, P < 0.001). CONCLUSION: Endoscope-assisted one-stage correction of the crooked nose can restore nasal morphology, improve the symptoms of nasal obstruction, and achieve patient satisfaction. It is a minimally invasive, safe, effective, and fast recovery approach for patients who need to solve both esthetic and functional problems.

M-Shaped Auricular Cartilage Grafts for Correcting Short Nose Deformity in Asians: A Retrospective Study.

BACKGROUND: The demand for rhinoplasty in Asia is growing annually, and short nose deformity has been one of the main reasons for the surgery due to its high incidence. There is an urgent need for rhinoplasty suitable for Asians because of their different facial features from Westerners. The M-shaped auricular cartilage rhinoplasty has been developed as a new method for correcting short nose deformity for Asians. This study aimed to evaluate the aesthetic and functional results of M-shaped auricular cartilage rhinoplasty compared to clinically commonly used rhinoplasty methods. METHODS: A total of 45 patients were enrolled and divided into three groups of 15 patients: The first group underwent M-shaped auricular cartilage rhinoplasty, the second group underwent auricular-septal cartilage rhinoplasty, and the third group underwent overlapped auricular cartilage rhinoplasty. All of these patients underwent comprehensive rhinoplasty and had silicone or expanded polytetrafluoroethylene implants in the dorsum of their noses. RESULTS: The patient score improvements on the three patient-reported outcome measures were higher in the M-shaped auricular cartilage rhinoplasty group (1.65/1.79/0.11) compared with the overlapped auricular cartilage rhinoplasty group (1.40/1.51/0.05), and the score improvements in the auricular-septal cartilage rhinoplasty group (2.04/1.98/0.28) were the highest. CONCLUSIONS: This is a retrospective clinical study demonstrating the clinical efficacy of M-shaped auricular cartilage rhinoplasty. Compared with the overlapped auricular cartilage rhinoplasty, the effect of this novel M-shaped method is better. However, when compared to the auricular-septal cartilage rhinoplasty with septal extension and reinforcement using nasal septal cartilage, its effect is slightly worse. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mechanisms regulating wound healing: Functional changes in biology mediated by lactate and histone lactylation.

The high incidence, low healing rate and huge economic burden of wounds (especially chronic wounds) worldwide remain a great challenge for clinical staff and patients. The various stages of wound healing are regulated by paracrine or autocrine cytokines and growth factors, and the study of their intrinsic mechanisms is a prerequisite for better wound treatment. Lactate, the end product of glycolysis, plays a role in all stages of wound healing, and recent studies have identified lactate as an epigenetic regulator that regulates gene expression through histone lysine lactylation and stimulates posttranslational modifications to regulate related gene expression, thereby causing a series of biological functional changes. This article reviews the progress of research on lactate and lactylation during wound healing or in related diseases, including its involvement in immune regulation, inflammation control, and proliferative remodeling, and finally describes the prospects for lactate therapy regarding wound healing.

Artificial Intelligence for Rhinoplasty Design in Asian Patients.

BACKGROUND: Rhinoplasty is one of the most challenging plastic surgeries because it lacks a uniform standard for preoperative design or implementation. For a long time, rhinoplasties were done without an accurate consensus of aesthetic design between surgeons and patients before surgery and consequently brought unsatisfactory appearance for patients. In recent years, three-dimensional (3D) simulation has been used to visualize the preoperative design of rhinoplasty, and good results have been achieved. However, it still relied on individual aesthetics and experience. The preoperative design remained a huge challenge for inexperienced surgeons and could be time-consuming to perform manually. Therefore, we adopted artificial intelligence (AI) in this work to provide a new idea for automated and efficient preoperative nasal contour design. METHODS: We collected a dataset of 3D facial images from 209 patients. For each patient, both the original face and the manually designed face using 3D simulation software were included. The 3D images were transformed into point clouds, based on which we used the modified FoldingNet model for deep neural network training (by pytorch 1.12). RESULTS: The trained AI model gained the ability to perform aesthetic design automatically and achieved similar results to manual design. We analysed the 1027 facial features captured by the AI model and concluded two of its possible cognitive modes. One is to resemble the human aesthetic considerations while the other is to fulfil the given task in a special way of the machine. CONCLUSION: We presented the first AI model for automated preoperative 3D simulation of rhinoplasty in this study. It provided a new idea for the automated, individual and efficient preoperative design, which was expected to bring a new paradigm for rhinoplasty and even the whole field of plastic surgery. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Correction of Short Nose Using M-shaped Cartilage in Asian Patients: Finite Element Analysis and Recommendations for Surgery.

BACKGROUND: Using M-shaped cartilage grafts is a new method for the correction of short nose deformity with good effect for Asians. Although the basic approach to M-shaped cartilage surgery is well understood, there is a great deal of uncertainty when plastic surgeons perform the procedure, and still a lack of standard guidance on the specific details. METHODS: In this study, the authors used finite element analysis to explore and compare postoperative cartilage stability of different fixing methods, different suturing positions, and different sizes of M-shaped cartilage. The authors applied a 0.01 N load to a 1 cm2 area of the nasal tip to simulate nasal tip palpation and compared the maximum deformations of different groups, which were used to make stability judgments. RESULTS: The maximum deformation of the model was the least when the M-shaped cartilage was fixed medially to the septal cartilage and laterally to the outer crura of the lower lateral cartilage. At the same time, the maximum deformation was the least when the M-shaped cartilage was sutured to the middle of the nasal septal cartilage. Besides, the length of M-shaped cartilage was preferably around 30 mm, while its width was not worthy of being overly concerned. CONCLUSIONS: For optimal postoperative stability of Asian short nose correction, the M-shaped cartilage should be sutured and fixed medially to the middle of the septal cartilage and laterally to the lateral crura of the lower lateral cartilage, and the length of the M-shaped cartilage should be controlled at around 30 mm. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Expanded forehead flap in Asian nasal reconstruction.

This article reviewed our experience of Chinese nasal reconstruction over 12 years and evaluated the effect of expanded forehead flap both aesthetically and functionally. The special skin type and other anatomic features of Chinese patients was understood thoroughly during the treatment. This article thus catered for the need of multiracial nasal reconstruction. We analyzed existing clinical data and demonstrated a typical case in detail. The postoperative result supported our strategy which advocated the extensive application of expanded forehead flap, together with flip scar flap as the internal lining. The features of Chinese patients also prompted the use of costal and auricular cartilage. Emerging technology like 3D-printing would benefit nasal reconstruction from more aspects.

Application of decellularization-recellularization technique in plastic and reconstructive surgery.

ABSTRACT: In the field of plastic and reconstructive surgery, the loss of organs or tissues caused by diseases or injuries has resulted in challenges, such as donor shortage and immunosuppression. In recent years, with the development of regenerative medicine, the decellularization-recellularization strategy seems to be a promising and attractive method to resolve these difficulties. The decellularized extracellular matrix contains no cells and genetic materials, while retaining the complex ultrastructure, and it can be used as a scaffold for cell seeding and subsequent transplantation, thereby promoting the regeneration of diseased or damaged tissues and organs. This review provided an overview of decellularization-recellularization technique, and mainly concentrated on the application of decellularization-recellularization technique in the field of plastic and reconstructive surgery, including the remodeling of skin, nose, ears, face, and limbs. Finally, we proposed the challenges in and the direction of future development of decellularization-recellularization technique in plastic surgery.

Exosomes of Adipose Tissue-Derived Stem Cells Promote Wound Healing by Sponging miR-17-5p and Inducing Autophagy Protein Ulk1.

BACKGROUND: Wound healing undergoes intricate phases: hemostasis, inflammation, proliferation, and remodeling. Stem cell therapy based on adipose tissue-derived stem cell exosomes (ADSCs-exo) is considered a potential effective treatment for accelerating wound healing. However, the molecular mechanisms of wound healing using ADSCs-exo remain largely unknown. METHODS: Circular wounds, 1 × 1 cm, were generated on C57BL/6 mice, followed by OriCell C57BL/6 mouse adipose-derived mesenchymal stem cell suspension treatment, and wound area was measured and recorded at days 0, 7, and 21, respectively. A comprehensive transcriptome profiling of skin wounds was conducted in the mouse model. Importantly, the authors also examined autophagy and cell migration in mouse keratinocytes treated with ADSCs-exo. Further competing endogenous RNA networks were also used to reveal the relationship between Neat1 and Ulk1 . RESULTS: Mouse keratinocytes treated with ADSCs-exo showed significant up-regulation of pathways related to wound healing, including response to virus, bacterium, immune system, and wounding. Activated autophagy was detected, which significantly promoted the wound repair of mice. Competing endogenous RNA networks uncovered that Neat1 induces the expression of Ulk1 and thus up-regulates autophagic activity to promote wound repair through sponging miR-17-5p. CONCLUSIONS: Collectively, these results reveal a novel molecular mechanism that the autophagy pathway enhanced by the Neat1 /miR-17-5p/ Ulk1 axis can promote the wound healing and suggest that long noncoding RNA Neat1 loaded by ADSCs-exo might be a potential therapeutic target for skin nonhealing wounds. CLINICAL RELEVANCE STATEMENT: This study may provide new clues for the applications of ADSCs-exo in skin wounds and promote the development of ADSCs-exo therapy in clinical treatment of skin wounds.