HIF-2α/TFR1 mediated iron homeostasis disruption aggravates cartilage endplate degeneration through ferroptotic damage and mtDNA release: A new mechanism of intervertebral disc degeneration.

Backgroud: Iron overload is a prevalent condition in the elderly, often associated with various degenerative diseases, including intervertebral disc degeneration (IDD). Nevertheless, the mechanisms responsible for iron ion accumulation in tissues and the mechanism that regulate iron homeostasis remain unclear. Transferrin receptor-1 (TFR1) serves as the primary cellular iron gate, playing a pivotal role in controlling intracellular iron levels, however its involvement in IDD pathogenesis and the underlying mechanism remains obscure. Methods: Firstly, IDD mice model was established to determine the iron metabolism associated proteins changes during IDD progression. Then CEP chondrocytes were isolated and treated with TBHP or pro-inflammatory cytokines to mimic pathological environment, western blotting, immunofluorescence assay and tissue staining were employed to explore the underlying mechanisms. Lastly, TfR1 siRNA and Feristatin II were employed and the degeneration of IDD was examined using micro-CT and immunohistochemical analysis. Results: We found that the IDD pathological environment, characterized by oxidative stress and pro-inflammatory cytokines, could enhance iron influx by upregulating TFR1 expression in a HIF-2α dependent manner. Excessive iron accumulation not only induces chondrocytes ferroptosis and exacerbates oxidative stress, but also triggers the innate immune response mediated by c-GAS/STING, by promoting mitochondrial damage and the release of mtDNA. The inhibition of STING through siRNA or the reduction of mtDNA replication using ethidium bromide alleviated the degeneration of CEP chondrocytes induced by iron overload. Conclusion: Our study systemically explored the role of TFR1 mediated iron homeostasis in IDD and its underlying mechanisms, implying that targeting TFR1 to maintain balanced iron homeostasis could offer a promising therapeutic approach for IDD management. The translational potential of this article: Our study demonstrated the close link between iron metabolism dysfunction and IDD, indicated that targeting TfR1 may be a novel therapeutic strategy for IDD.

High-precision 3D printing of multi-branch vascular scaffold with plasticized PLCL thermoplastic elastomer.

Three-dimensional (3D) printing has emerged as a transformative technology for tissue engineering, enabling the production of structures that closely emulate the intricate architecture and mechanical properties of native biological tissues. However, the fabrication of complex microstructures with high accuracy using biocompatible, degradable thermoplastic elastomers poses significant technical obstacles. This is primarily due to the inherent soft-matter nature of such materials, which complicates real-time control of micro-squeezing, resulting in low fidelity or even failure. In this study, we employ Poly (L-lactide-co-ϵ-caprolactone) (PLCL) as a model material and introduce a novel framework for high-precision 3D printing based on the material plasticization process. This approach significantly enhances the dynamic responsiveness of the start-stop transition during printing, thereby reducing harmful errors by up to 93%. Leveraging this enhanced material, we have efficiently fabricated arrays of multi-branched vascular scaffolds that exhibit exceptional morphological fidelity and possess elastic moduli that faithfully approximate the physiological modulus spectrum of native blood vessels, ranging from 2.5 to 45 MPa. The methodology we propose for the compatibilization and modification of elastomeric materials addresses the challenge of real-time precision control, representing a significant advancement in the domain of melt polymer 3D printing. This innovation holds considerable promise for the creation of detailed multi-branch vascular scaffolds and other sophisticated organotypic structures critical to advancing tissue engineering and regenerative medicine.

Embedding Quantum Many-Body Scars into Decoherence-Free Subspaces.

Quantum many-body scars are nonthermal excited eigenstates of nonintegrable Hamiltonians, which could support coherent revival dynamics from special initial states when scars form an equally spaced tower in the energy spectrum. For open quantum systems, engineering many-body scarred dynamics by a controlled coupling to the environment remains largely unexplored. Here, we provide a general framework to exactly embed quantum many-body scars into the decoherence-free subspaces of Lindblad master equations. The dissipative scarred dynamics manifest persistent periodic oscillations for generic initial states, and can be practically utilized to prepare scar states with potential quantum metrology applications. We construct the Liouvillian dissipators with the local projectors that annihilate the whole scar towers, and utilize the Hamiltonian part to rotate the undesired states out of the null space of dissipators. We demonstrate our protocol through several typical models hosting many-body scar towers and propose an experimental scheme to observe the dissipative scarred dynamics based on digital quantum simulations and resetting ancilla qubits.

Association of Vitamin D Levels with Risk of Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Prospective Studies.

Background: Emerging evidence suggests the potential relationship between vitamin D deficiency and risk of cognitive impairment or dementia. To what extent the excess risk of dementia conferred by vitamin D deficiency is less clear. Objective: We summarized the current evidence from several aspects and further quantified these associations. Methods: We collected relevant prospective cohort studies by searching PubMed, Embase and Cochrane up to July 2023. The pooled relative risks (RR) were evaluated by random-effects models. Dose-response analyses were conducted by the method of two-stage generalized least squares regression. Results: Of 9,267 identified literatures, 23 were eligible for inclusion in the meta-analyses, among which 9 and 4 literatures were included in the dose-response analyses for the risk of dementia and Alzheimer's disease (AD). Vitamin D deficiency exhibited a 1.42 times risk for dementia (95% confidence interval (CI) = 1.21-1.65) and a 1.57-fold excess risk for AD (95% CI = 1.15-2.14). And vitamin D deficiency was associated with 34% elevated risk with cognitive impairment (95% CI = 1.19-1.52). Additionally, vitamin D was non-linearly related to the risk of dementia (pnonlinearity = 0.0000) and AD (pnonlinearity = 0.0042). The approximate 77.5-100 nmol/L 25-hydroxyvitamin D [25(OH)D] was optimal for reducing dementia risk. And the AD risk seemed to be decreased when the 25(OH)D level >40.1 nmol/L. Conclusions: Vitamin D deficiency was a risk factor for dementia, AD, and cognitive impairment. The nonlinear relationships may further provide the optimum dose of 25(OH)D for dementia prevention.

Quantitative Biofabrication Platform for Collagen-Based Peripheral Nerve Grafts with Structural and Chemical Guidance.

Owing to its crucial role in the human body, collagen has immense potential as a material for the biofabrication of tissues and organs. However, highly refined fabrication using collagen remains difficult, primarily because of its notably soft properties. A quantitative biofabrication platform to construct collagen-based peripheral nerve grafts, incorporating bionic structural and chemical guidance cues, is introduced. A viscoelastic model for collagen, which facilitates simulating material relaxation and fabricating collagen-based neural grafts, achieving a maximum channel density similar to that of the native nerve structure of longitudinal microchannel arrays, is established. For axonal regeneration over considerable distances, a gradient printing control model and quantitative method are developed to realize the high-precision gradient distribution of nerve growth factor required to obtain nerve grafts through one-step bioprinting. Experiments verify that the bioprinted graft effectively guides linear axonal growth in vitro and in vivo. This study should advance biofabrication methods for a variety of human tissue-engineering applications requiring tailored cues.

Activation of the Nrf-2 pathway by pinocembrin safeguards vertebral endplate chondrocytes against apoptosis and degeneration caused by oxidative stress.

AIM: The occurrence and progression of intervertebral disc degeneration (IDD) are significantly influenced by the cartilaginous endplate (CEP). Pinocembrin (PIN), a type of flavonoid present in propolis and botanicals, demonstrates both antioxidant and anti-inflammatory characteristics, which could potentially be utilized in management. Therefore, it is crucial to investigate how PIN protects against CEP degeneration and its mechanisms, offering valuable insights for IDD therapy. MATERIALS AND METHODS: To investigate the protective impact of PIN in vivo, we created the IDD mouse model through bilateral facet joint transection. In vitro, an IDD pathological environment was mimicked by applying TBHP to treat endplate chondrocytes. KEY FINDINGS: In vivo, compared with the IDD group, the mouse in the PIN group effectively mitigates IDD progression and CEP calcification. In vitro, the activation of the Nrf-2 pathway improves the process of Parkin-mediated autophagy in mitochondria and decreases ferroptosis in chondrocytes. This enhancement promotes cell survival by addressing the imbalance of redox during pathological conditions related to IDD. Knocking down Nrf-2 with siRNA fails to provide protection to endplate chondrocytes against apoptosis and degeneration. SIGNIFICANCE: The Nrf-2-mediated activation of mitochondrial autophagy and suppression of ferroptosis play a crucial role in safeguarding against oxidative stress-induced degeneration and calcification of CEP through the protective function of PIN. To sum up, this research offers detailed explanations about how PIN can protect against apoptosis and calcification in CEP, providing valuable information about the development of IDD and suggesting possible treatment approaches.

Fabrication of Multi-Channel Nerve Guidance Conduits Containing Schwann Cells Based on Multi-Material 3D Bioprinting.

Nerve guidance conduits (NGCs) are an essential solution for peripheral nerve repair and regeneration in tissue engineering and medicine. However, the ability of current NGCs is limited to repairing longer nerve gap (i.e., >20 mm) because it cannot meet the following two conditions simultaneously: (1) directional guidance of the axial high-density channels and (2) regenerative stimulation of the extracellular matrix secreted by Schwann cells (SCs). Therefore, we propose a multi-material 3D bioprinting process to fabricate multi-channel nerve guide conduits (MNGCs) containing SCs. In the article, cell-laden methacrylate gelatin (GelMA) was used as the bulk material of MNGCs. To improve the printing accuracy of the axial channels and the survival rate of SCs, we systematically optimized the printing temperature parameter based on hydrogel printability analysis. The multi-material bioprinting technology was used to realize the alternate printing of supporting gelatin and cell-laden GelMA. Then, the high-accuracy channels were fabricated through the UV cross-linking of GelMA and the dissolving technique of gelatin. The SCs distributed around the channels with a high survival rate, and the cell survival rate maintained above 90%. In general, the study on multi-material 3D printing was carried out from the fabricating technology and material analysis, which will provide a potential solution for the fabrication of MNGCs containing SCs.

Design and evaluation of a stick-slip piezoelectric actuator with flexure hinge mechanism inspired by the earthworm.

In this work, a new bionic piezoelectric actuator inspired by the earthworm is proposed, fabricated, and tested. The operating principle of the actuator imitates the crawling motion of the earthworm. The piezoelectric stack is embedded in the stator with a flexure hinge mechanism. One side of the stator is inspired by the earthworm body. Then the elongation of the piezoelectric stack is transmitted to the driving tip to produce oblique displacement under such a stator. The vertical and horizontal components are used to press and drive the slider, respectively. The principle of the proposed actuator is described in detail. The static deformation is investigated by the FEM method. A dynamic model of the actuator is developed to further reveal the motion characteristics of the slider via theoretical analysis. Finally, the output characteristics of the proposed BPA are tested. The experimental results show that the actuator achieves a maximum output speed of 12.72 mm/s at a voltage of 100 V and a frequency of 710 Hz. The maximum output force is 3 N under a locking force of 2 N. Besides, the displacement resolution is tested at 87 nm at a frequency of 710 Hz, which indicates that the developed actuator can be applied in the field of precision actuation.

Design and evaluation of a magnetically coupled piezoelectric energy harvester with parallel connection.

This work proposed a magnetically coupled piezoelectric energy harvester with parallel connections. The rectangular piezoelectric patch in the upper part of the device generates regular vibrations due to the nonlinear forces caused by magnetic coupling. The lower rectangular piezoelectric patch is deformed by contact collision excitation. The parallel connection effectively connects the two sets of piezoelectric patches together and fully exploits the performance of the piezoelectric energy harvester. The intrinsic frequency of the rectangular piezoelectric patch was simulated and verified experimentally. The rectangular piezoelectric patch generates a large vibration amplitude in high-speed operation due to its elasticity property. From the experimental results, it can be seen that the piezoelectric energy harvester can work well in different frequency bands. The parallel piezoelectric energy harvester with a three-contact rotor has a peak-to-peak voltage of 252 V at a speed of 120 r/min and 200 V at a speed of 240 r/min. The maximum voltage achieved by the piezoelectric energy harvester in parallel is 266 V at a speed of 180 r/min with a resistance of 1000 kΩ. The maximum voltage reached by a series-connected piezoelectric energy harvester is 256 V at a speed of 180 r/min and a resistance of 100 kΩ. The peak-to-peak power of the piezoelectric energy harvester connected in parallel is 0.313 W under a resistance of 100 kΩ and a speed of 180 r/min. Besides, the developed piezoelectric energy harvester can light up to 60 light-emitting diodes. Accordingly, the energy can be effectively harvested by the piezoelectric energy harvester and then supplied to the microelectronic device.

Family history and breast cancer risk for Asian women: a systematic review and meta-analysis.

BACKGROUND: Studies of women of European ancestry have shown that the average familial relative risk for first-degree relatives of women with breast cancer is approximately twofold, but little is known for Asian women. We aimed to provide evidence for the association between family history and breast cancer risk for Asian women by systematically reviewing published literature. METHODS: Studies reporting the familial relative risk of breast cancer for Asian women were searched in three online databases and complemented by a manual search. Odds ratios (ORs) for the association between family history and breast cancer risk were pooled across all included studies and by subgroups in terms of the type of family history, age, menopausal status and geographical region. RESULTS: The pooled OR for women who have a first-degree relative with breast cancer was 2.46 (95% confidence interval [CI]: 2.03, 2.97). There was no evidence that the familial risk differed by the type of affected relative (mother versus sisters), the woman's age (< 50 years versus ≥ 50 years), menopausal status (pre versus post) and geographical region (East and Southeast Asia versus other regions) (all P > 0.3). The pooled ORs for women of Asian ancestry with a family history in any relative were similar for those living in non-Asian countries (2.26, 95% CI: 1.42, 3.59) compared with those living in Asian countries (2.18, 95% CI: 1.85, 2.58). CONCLUSIONS: Family history of breast cancer is associated with an approximately twofold relative risk of breast cancer for Asian women, which is of similar magnitude to that observed for women of European ancestry. This implies that similar familial factors are implicated in breast cancer risk between women of European and Asian ancestries. Genetic factors are likely to play a substantial role in explaining the breast cancer familial risk for Asian women, as similar risks were observed across different living environments and cultures.

Development of a Novel Piezoelectric Actuator Based on Stick-Slip Principle by Using Asymmetric Constraint.

In this work, a novel piezoelectric actuator based on the stick-slip principle is proposed. The actuator is constrained by an asymmetric constraint approach; the driving foot produces lateral and longitudinal coupling displacements when the piezo stack is extended. The lateral displacement is used to drive the slider and the longitudinal displacement is used to compress the slider. The stator part of the proposed actuator is illustrated and designed by simulation. The operating principle of the proposed actuator is described in detail. The feasibility of the proposed actuator is verified by theoretical analysis and finite element simulation. A prototype is fabricated and some experiments are carried out to study the proposed actuator's performance. The experimental results show that the maximum output speed of the actuator is 3680 µm/s when the locking force is 1 N under the voltage of 100 V and frequency of 780 Hz. The maximum output force is 3.1 N when the locking force is 3 N. The displacement resolution of the prototype is measured as 60 nm under the voltage of 15.8 V, frequency of 780 Hz and locking force of 1 N.

Research on preparation and antitumor activity of redox-responsive polymer micelles co-loaded with sorafenib and curcumin.

A novel redox-responsive mPEG-SS-PLA (PSP) polymeric micelle was synthesized and prepared for the delivery of sorafenib (SAF) and curcumin (CUR). And a series of validations were conducted to confirm the structure of the synthesized polymer carriers. Using the Chou-Talalay approach, the combination indexes (CI) of SAF and CUR were determined, and explore the inhibitory effects of the two drugs on HepG2R cells at different ratios. SAF/CUR-PSP polymeric micelles were prepared by thin film hydration method, and the physicochemical properties of nanomicelles were evaluated. The biocompatibility, cell uptake, cell migration, and cytotoxicity assays were assessed in HepG2R cells. The expression of the phosphoinositol-3 kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway was detected by Western blot assay. Additionally, the tumor suppressive effect of SAF/CUR-PSP micelles was clearly superior to free drug monotherapy or their physical combination in HepG2 cell-induced tumor xenografts. The current study revealed that mPEG-SS-PLA polymer micelles loaded with SAF and CUR showed the enhanced therapeutic effects against hepatocellular carcinoma in vitro and in vivo models. It has promising applications for cancer therapy.

Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2/HO-1 signaling pathway.

BACKGROUND: Cartilage endplate (CEP) degeneration is an important initiating factor leading to intervertebral disc degeneration (IVDD). Astaxanthin (Ast) is a natural lipid-soluble and red-orange carotenoid which possesses various biological activities, including antioxidant, anti-inflammatory, and anti-aging effects in multiple organisms. However, the effects and mechanism of Ast on endplate chondrocytes remain largely unknown. The objective of the current study was to investigate the effects and of Ast on CEP degeneration and its underlying molecular mechanisms. METHODS: Tert-butyl hydroperoxide (TBHP) was used to mimic the IVDD pathological environment. We investigated the effects of Ast on the Nrf2 signaling pathway and damage-associated events. The IVDD model was constructed by surgical resection of L4 posterior elements to explore the role of Ast in vivo. RESULTS: We found that the activation of the Nrf-2/HO-1 signaling pathway was enhanced by Ast, thus promoted mitophagy process, inhibited oxidative stress and CEP chondrocytes ferroptosis, eventually ameliorated extracellular matrix (ECM) degradation, CEP calcification and endplate chondrocytes apoptosis. Knockdown of Nrf-2 using siRNA inhibited Ast induced mitophagy process and its protective effect. Moreover, Ast inhibited oxidative stimulation-induced NF-κB activity and could ameliorate the inflammation response. The results also were confirmed by experiments in vivo, Ast alleviated IVDD development and CEP calcification. CONCLUSIONS: Ast could protect vertebral cartilage endplate against oxidative stress and degeneration via activating Nrf-2/HO-1 pathway. Our results imply that Ast may serve as a potential therapeutic agent for IVDD progression and treatment.

Development of a piezoelectric actuator based on stick-slip principle inspired by the predation of snake.

A new piezoelectric actuator based on the stick-slip working principle inspired by the predation of the snake is proposed and developed in this work. A lead zirconate titanate (PZT) stack is used and inserted into the stator with an asymmetric configuration. Then, the elongation of the PZT stack can be transmitted into the vertical and horizontal displacements on the driving foot. They are used to press and drive the slider, respectively. In this design, the motion of the actuator imitates the predation process of the snake. The principle of the proposed actuator is clarified in detail. The statics characteristics are conducted by using the FEM method. The dynamics model of the actuator was established to show the motion behavior of the slider in theory. Finally, the output characteristics of the developed piezoelectric actuator are tested. The results stated that this actuator obtained the maximum output speed of 11.44 mm/s under a voltage of 100 V and a frequency of 600 Hz. The output force of the developed actuator was 2.8N under the preload force of 3N. In conclusion, the feasibility of the proposed piezoelectric stick-slip type actuator inspired by the predation of the snake is verified.

Clinical Characteristics of Minimal Lumbar Disc Herniation and Efficacy of Percutaneous Endoscopic Lumbar Discectomy via Transforaminal Approach: A Retrospective Study.

OBJECTIVE: To define the characteristics of Mini LDH, develop new diagnostic references and examine the clinical efficacy of percutaneous endoscopic lumbar discectomy via a transforaminal approach (TF-PELD) for it. METHODS: A total of 72 patients who underwent TF-PELD with Mini LDH from September 2019 to October 2022 were enrolled in this retrospective study. The patients' basic information, symptoms, number of outpatient visits, duration of conservative treatment, physical examination findings and so on were obtained from the medical records. Clinical effects of TF-PELD for Mini LDH were assessed by means of the following: the Visual Analog Scale (VAS) for low back pain (LBP) and leg pain, Oswestry Disability Index (ODI) for functional status assessment and Modified Mac Nab criteria for patient satisfaction. RESULTS: Mini LDH have specific clinical characteristics and imaging features. All included patients achieved obvious pain relief after TF-PELD surgery. Pain scores were repeated at postoperative day 1 and 1, 3, 6, 12 and 24 months later. Results were statistically analyzed. The average VAS-Back, VAS-Leg and ODI scores were all significantly reduced at the first postoperative day and gradually decreased with the follow-up time continuing. In total, 66 out of 72 patients received an excellent or good recovery and no poor result was reported according to the Modified Mac Nab criteria. CONCLUSIONS: Mini LDH is a type of LDH with special characteristics and in need of correct diagnosis and active treatment in clinical work. TF-PELD was also found to be an effective procedure for the treatment of Mini LDH.

Bioprinting of light-crosslinkable neutral-dissolved collagen to build implantable connective tissue with programmable cellular orientation.

Fabricating connective tissue with printing fidelity, structural stability, biocompatibility, and cellular orientation remains a challenge for bioink. Collagen, as inherent fibers to provide strengthin vivo, should be the ideal material for tissue printing. However, current collagen-bioink exhibits poor printability and mechanical properties. Here, the light-crosslinkable norbornene-collagen (NorCol) is developed to solve this dilemma. NorCol with complete collagen structure exhibits outstanding shear-thinning properties and light-crosslinking strength, realizing the construction of complicated constructs with excellent printing fidelity and structural stability. Neutral-dissolved NorCol with different concentrations is directly integrated to print pure collagen structure with composite modulus, providing top-class biocompatibility that mimics the heterogeneous microarchitecture of the extracellular matrix (ECM). This composite structure also permits extensive infiltration of host tissue and capillaries during subcutaneous transplants. By the designed tight interface of printed filaments, a geometric-guided and modulus-independent anisotropic mechanical environment is constructed, realizing cellular orientation. Furthermore, the cellular orientation is in the same direction as the printed high-concentration NorCol, which is the same case of cells and collagen fibersin vivo. This capability of NorCol breaks new ground for printing pure ECM protein-based, implantable and functional constructs, applicable in connective tissue engineering for human applications.

Vascularized organ bioprinting: From strategy to paradigm.

Over the past two decades, 3D bioprinting has become a popular research topic worldwide, as it is the most promising approach for manufacturing vascularized organs in vitro. However, transitioning from bioprinting of simple tissue models to real biomedical applications is still a challenge due to incomplete interdisciplinary theoretical knowledge and imperfect multi-technology integration. This review examines the goals of vasculature manufacturing and proposes new strategic objectives in three stages. We then outline a bidirectional manufacturing strategy consisting of top-down reconstruction (bioprinting) and bottom-up regeneration (cellular behaviour). We also provide an in-depth analysis of the four aspects of design, ink, printing and culture. Furthermore, we present the 'construction-comprehension cycle' research paradigm and the 'math-model-based batch insights generator' research paradigm for the future, which may have the potential to revolutionize the biomedical field.

Methotrexate showed efficacy both in Crohn's disease and ulcerative colitis, predictors of surgery were identified in patients initially treated with methotrexate monotherapy.

Objective: This study aimed to evaluate methotrexate efficacy in patients with Crohn's disease (CD) and ulcerative colitis (UC), and identify predictors of surgery for patients who were initially treated with methotrexate monotherapy. Design: We performed a retrospective analysis of 34,860 patients with inflammatory bowel disease (IBD) in the IBD Bioresource (United Kingdom) prior to 9 November 2021. Logistic regression was used to identify factors associated with methotrexate efficacy. The data were randomly stratified into training and testing sets (7:3). Nomograms were developed based on Cox regression analysis outcomes. The predictive accuracy and discriminative ability were determined using the concordance index (C-index) and calibration curves. Results: Overall, 1,042 patients (CD: 791, UC: 251) were included. Independent factors associated with effective methotrexate monotherapy were younger age at diagnosis, latest therapy period, exclusive upper gastrointestinal tract disease (for CD), and longer duration between diagnosis and methotrexate initiation (for UC). For CD, predictors in the nomogram were gender, treatment era, tolerance, lesion site, perianal involvement, disease behaviour, and biologics requirements (C-index: 0.711 and 0.732 for training and validation cohorts, respectively). For UC, the factors were age at diagnosis and sex (C-index: 0.784 and 0.690 for training and validation cohorts, respectively). Calibration curves demonstrated good agreement between predictions and actual observations.

Large full-thickness wounded skin regeneration using 3D-printed elastic scaffold with minimal functional unit of skin.

Traditional tissue engineering skin are composed of living cells and natural or synthetic scaffold. Besize the time delay and the risk of contamination involved with cell culture, the lack of autologous cell source and the persistence of allogeneic cells in heterologous grafts have limited its application. This study shows a novel tissue engineering functional skin by carrying minimal functional unit of skin (MFUS) in 3D-printed polylactide-co-caprolactone (PLCL) scaffold and collagen gel (PLCL + Col + MFUS). MFUS is full-layer micro skin harvested from rat autologous tail skin. 3D-printed PLCL elastic scaffold has the similar mechanical properties with rat skin which provides a suitable environment for MFUS growing and enhances the skin wound healing. Four large full-thickness skin defects with 30 mm diameter of each wound are created in rat dorsal skin, and treated either with tissue engineering functional skin (PLCL + Col + MFUS), or with 3D-printed PLCL scaffold and collagen gel (PLCL + Col), or with micro skin islands only (Micro skin), or without treatment (Normal healing). The wound treated with PLCL + Col + MFUS heales much faster than the other three groups as evidenced by the fibroblasts migration from fascia to the gap between the MFUS dermis layer, and functional skin with hair follicles and sebaceous gland has been regenerated. The PLCL + Col treated wound heals faster than normal healing wound, but no skin appendages formed in PLCL + Col-treated wound. The wound treated with micro skin islands heals slower than the wounds treated either with tissue engineering skin (PLCL + Col + MFUS) or with PLCL + Col gel. Our results provide a new strategy to use autologous MFUS instead "seed cells" as the bio-resource of engineering skin for large full-thickness skin wound healing.