Fluffy hybrid nanoadjuvants for reversing the imbalance of osteoclastic and osteogenic niches in osteoporosis.

Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their low bioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. This calls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybrid structures with bioactive components and stable fluffy topological morphology by cross-linking calcium and phosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequent grafting of -PEG-DAsp8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealed that these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecular mechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that small-dose AL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivo results restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as the consequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant with peculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well as bone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies for other bone diseases.

VR23 and Bisdemethoxycurcumin Enhanced Nanofiber Niche with Durable Bidirectional Functions for Promoting Wound Repair and Inhibiting Scar Formation.

Chronic wounds pose a significant clinical challenge worldwide, which is characterized by impaired tissue regeneration and excessive scar formation due to over-repair. Most studies have focused on developing wound repair materials that either facilitate the healing process or control hyperplastic scars caused by over-repair, respectively. However, there are limited reports on wound materials that can both promote wound healing and prevent scar hyperplasia at the same time. In this study, VR23-loaded dendritic mesoporous bioglass nanoparticles (dMBG) are synthesized and electrospun in poly(ester-curcumin-urethane)urea (PECUU) random composite nanofibers (PCVM) through the synergistic effects of physical adsorption, hydrogen bond, and electrospinning. The physicochemical characterization reveals that PCVM presented matched mechanical properties, suitable porosity, and wettability, and enabled sustained and temporal release of VR23 and BDC with the degradation of PCVM. In vitro experiments demonstrated that PCVM can modulate the functions and polarization of macrophages under an inflammatory environment, and possess effective anti-scarring potential and reliable cytocompatibility. Animal studies further confirmed that PCVM can efficiently promote re-epithelialization and angiogenesis and reduce excessive inflammation, thereby remarkably accelerating wound healing while preventing potential scarring. These findings suggest that the prepared PCVM holds promise as a bidirectional regulatory dressing for effectively promoting scar-free healing of chronic wounds.

Durable immunomodulatory hierarchical patch for rotator cuff repairing.

Degradable rotator cuff patches, followed over five years, have been observed to exhibit high re-tear rates exceeding 50%, which is attributed to the inability of degradable polymers alone to restore the post-rotator cuff tear (RCT) inflammatory niche. Herein, poly(ester-ferulic acid-urethane)urea (PEFUU) was developed, featuring prolonged anti-inflammatory functionality, achieved by the integration of ferulic acid (FA) into the polyurethane repeating units. PEFUU stably releases FA in vitro, reversing the inflammatory niche produced by M1 macrophages and restoring the directed differentiation of stem cells. Utilizing PEFUU, hierarchical composite nanofiber patch (HCNP) was fabricated, simulating the natural microstructure of the tendon-to-bone interface with an aligned-random alignment. The incorporation of enzymatic hydrolysate derived from decellularized Wharton jelly tissue into the random layer could further enhance cartilage regeneration at the tendon-to-bone interface. Via rat RCT repairing model, HCNP possessing prolonged anti-inflammatory properties uniquely facilitated physiological healing at the tendon-to-bone interface's microstructure. The alignment of fibers was restored, and histologically, the characteristic tripartite distribution of collagen I - collagen II - collagen I was achieved. This study offers a universal approach to the functionalization of degradable polymers and provides a foundational reference for their future applications in promoting the in vivo regeneration of musculoskeletal tissues.

Study on PTFE superhydrophobic coating modified by IC@dMSNs and its enhanced antibacterial effect.

INTRODUCTION: Vascular catheter-related infections and thrombosis are common and may lead to serious complications after catheterization. Reducing the incidence of such infections has become a significant challenge. OBJECTIVES: This study aims to develop a super hydrophobic nanocomposite drug-loaded vascular catheter that can effectively resist bacterial infections and blood coagulation. METHODS: In this study, a SiO2 nanocoated PTFE (Polytetrafluoroethylene) catheter (PTFE-SiO2) was prepared and further optimized to prepare a SiO2 nanocoated PTFE catheter loaded with imipenem/cilastatin sodium (PTFE-IC@dMSNs). The catheters were characterized for performance, cell compatibility, anticoagulant performance, in vitro and in vivo antibacterial effect and biological safety. RESULTS: PTFE-IC@dMSNs catheter has efficient drug loading performance and drug release rate and has good cell compatibility and anticoagulant effect in vitro. Compared with the PTFE-SiO2 catheter, the inhibition ring of the PTFE-IC@dMSNs catheter against Escherichia coli increased from 3.98 mm2 to 4.56 mm2, and the antibacterial rate increased from about 50.8 % to 56.9 %, with a significant difference (p < 0.05). The antibacterial zone against Staphylococcus aureus increased from 8.63 mm2 to 11.74 mm2, and the antibacterial rate increased from approximately 83.5 % to 89.3 %, showing a significant difference (p < 0.05). PTFE-IC@dMSNs catheter also has good biocompatibility in vivo. Furthermore, the PTFE-IC@dMSNs catheter can reduce the adhesion of blood cells and have excellent anticoagulant properties, and even maintain these properties even with the addition of imipenem/cilastatin sodium. CONCLUSION: Compared with PTFE, PTFE-SiO2 and PTFE-IC@dMSNs catheters have good characterization performance, cell compatibility, and anticoagulant properties. PTFE SiO2 and PTFE-IC@dMSNs catheters have good antibacterial performance and tissue safety against E. coli and S. aureus. Relatively, PTFE-SiO2 and PTFE-IC@dMSNs catheter has better antibacterial properties and histocompatibility and has potential application prospects in anti-bacterial catheter development and anticoagulation.

Highly Bioadaptable Hybrid Conduits with Spatially Bidirectional Structure for Precision Nerve Fiber Regeneration via Gene Therapy.

Peripheral nerve deficits give rise to motor and sensory impairments within the limb. The clinical restoration of extensive segmental nerve defects through autologous nerve transplantation often encounters challenges such as axonal mismatch and suboptimal functional recovery. These issues may stem from the limited regenerative capacity of proximal axons and the subsequent Wallerian degeneration of distal axons. To achieve the integration of sensory and motor functions, a spatially differential plasmid DNA (pDNA) dual-delivery nanohydrogel conduit scaffold is devised. This innovative scaffold facilitates the localized administration of the transforming growth factor ß (TGF-ß) gene in the proximal region to accelerate nerve regeneration, while simultaneously delivering nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) to the distal region to mitigate Wallerian degeneration. By promoting autonomous and selective alignment of nerve fiber gap sutures via structure design, the approach aims to achieve a harmonious unification of nerve regeneration, neuromotor function, and sensory recovery. It is anticipated that this groundbreaking technology will establish a robust platform for gene delivery in tissue engineering.

Fabric-Enhanced Vascular Graft with Hierarchical Structure for Promoting the Regeneration of Vascular Tissue.

Natural blood vessels have completed functions, including elasticity, compliance, and excellent antithrombotic properties because of their mature structure. To replace damaged blood vessels, vascular grafts should perform these functions by simulating the natural vascular structures. Although the structures of natural blood vessels are thoroughly explored, constructing a small-diameter vascular graft that matches the mechanical and biological properties of natural blood vessels remains a challenge. A hierarchical vascular graft is fabricated by Electrospinning, Braiding, and Thermally induced phase separation (EBT) processes, which could simulate the structure of natural blood vessels. The internal electrospun structure facilitates the adhesion of endothelial cells, thereby accelerating endothelialization. The intermediate PLGA fabric exhibits excellent mechanical properties, which allow it to maintain its shape during long-term transplantation and prevent graft expansion. The external macroporous structure is beneficial for cell growth and infiltration. Blood vessel remodeling aims to combine a structure that promotes tissue regeneration with anti-inflammatory materials. The results in vitro demonstrated that it EBT vascular graft (EBTVG) has matched the mechanical properties, reliable cytocompatibility, and the strongest endothelialization in situ. The results in vitro and replacement of the resected artery in vivo suggest that the EBTVG combines different structural advantages with biomechanical properties and reliable biocompatibility, significantly promoting the stabilization and regeneration of vascular endothelial cells and vascular smooth muscle cells, as well as stabilizing the blood microenvironment.

Biomimetic short fiber reinforced 3-dimensional scaffold for bone tissue regeneration.

Bone defects caused by diseases and trauma are considered serious clinical challenges. Autologous and allogeneic transplantations are the most widely used methods to mitigate bone defects. However, transplantation poses risks such as secondary trauma, immune rejection, and disease transmission to patients. Preparing a biologically active bone tissue engineering scaffold as a bone substitute can overcome this problem. In the current study, a PLGA/gelatin (Gel) short fiber-reinforced composite three-dimensional (3D) scaffold was fabricated by electrospinning for bone tissue defect repair. A hybrid scaffold adding inorganic materials hydrotalcite (CaAl-LDH) and osteogenic factors deferoxamine (DFO) based on PLGA and Gel composite filaments was prepared. The structure, swelling, drug release, and compressive resilience performance of the 3D scaffolds in a wet state were characterized and the osteogenic effect of the crosslinked scaffold (C-DLPG) was also investigated. The scaffold has shown the optimum physicochemical attributes which still has 380 kPa stress after a 60% compression cycle and sustainedly released the drug for about twenty days. Moreover, a promisingIn vivoosteogenic performance was noted with better tissue organization. At 8 weeks after implantation, the C-DLPG scaffold could fill the bone defect site, and the new bone area reached 19 mm2. The 3D microfiber scaffold, in this study, is expected to be a promising candidate for the treatment of bone defects in the future.

Durable Immunomodulatory Nanofiber Niche for the Functional Remodeling of Cardiovascular Tissue.

Functional remodeling and prolonged anti-inflammatory responses are both vital for repairing damage in the cardiovascular system. Although these aspects have each been studied extensively alone, attempts to fabricate scaffolds that combine these effects have seen limited success. In this study, we synthesized salvianic acid A (SA, danshensu) blocked biodegradable polyurethane (PCHU-D) and enclosed it within electrospun nanofibers to synthesize a durable immunomodulatory nanofiber niche (DINN), which provided sustained SA release during inflammation. Given its excellent processability, mechanical properties, and shape memory function, we developed two variants of the DINN as vascular scaffolds and heart patches. Both these variants exhibited outstanding therapeutic effects in in vivo experiments. The DINN was expertly designed such that it gradually decomposes along with SA release, substantially facilitating cellular infiltration and tissue remodeling. Therefore, the DINN effectively inhibited the migration and chemotaxis of inflammatory cells, while also increasing the expression of angiogenic genes. As a result, it promoted the recovery of myocardial function after myocardial infarction and induced rapid reendothelialization following arterial orthotopic transplantation repair. These excellent characteristics indicate that the DINN holds great potential as a multifunctional agent for repairing cardiovascular tissues.

Electrospun compliant heparinized elastic vascular graft for improving the patency after implantation.

The low patency rate after artificial blood vessel replacement is mainly due to the ineffective use of anticoagulant factors and the mismatch of mechanical compliance after transplantation. Electrospun nanofibers with biomimetic extracellular matrix three-dimensional structure and tunable mechanical strength are excellent carriers for heparin. In this work, we have designed and synthesized a series of biodegradable poly(ester-ether-urethane)ureas (BEPU), following compound with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid BEPU/heparin nanofibers tubular graft for replacing rats' abdominal aorta in situ for comprehensive performance evaluation. The results in vitro demonstrated that the electrospun L-PEUUH (LDI-based PEUU with heparin) vascular graft was of regular microstructure, optimum surface wettability, matched mechanical properties, reliable cytocompatibility, and strongest endothelialization in situ. Replacement of resected abdominal artery with the L-PEUUH vascular graft in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), as well as stabilizing the blood microenvironment. This research demonstrates the L-PEUUH vascular graft with substantial patency, indicating their potential for injured vascular healing.

A multifunctional chitosan composite aerogel based on high density amidation for chronic wound healing.

The management of chronic wounds remains a challenging clinical problem worldwide, mainly because of secondary infections, excessive oxidative stress, and blocked angiogenesis. Aerogel is a novel material with high porosity and specific surface area that allows gas exchange and rapid absorption of a large amount of exudate as well as loading bioactive molecules. Therefore, functional aerogel can be an ideal material for chronic wound treatment. The multifunctional aerogel (CG-DA-VEGF) was prepared by a simple and eco-friendly freeze-drying process combined with harmless EDC/NHS as crosslinking agents using chitosan and dopamine-grafted gelatin as raw materials. The physicochemical characterization revealed that the CG-DA-VEGF aerogel had excellent water absorption, water retention, and mechanical properties, and could release VEGF continuously and stably. In vitro experiments demonstrated that the CG-DA-VEGF aerogel exhibited effective antioxidant and antibacterial properties, as well as superb cytocompatibility. In vivo experiments further confirmed that the CG-DA-VEGF aerogel could significantly improve angiogenesis and re-epithelialization, and promote collagen deposition, thus accelerating wound healing with excellent biosafety. These results suggest that the as-prepared CG-DA-VEGF aerogel may be adopted as a promising multifunctional graft for the treatment of chronic wounds.

Bi-lineage inducible and immunoregulatory electrospun fibers scaffolds for synchronous regeneration of tendon-to-bone interface.

Facilitating regeneration of the tendon-to-bone interface can reduce the risk of postoperative retear after rotator cuff repair. Unfortunately, undesirable inflammatory responses following injury, difficulties in fibrocartilage regeneration, and bone loss in the surrounding area are major contributors to suboptimal tendon-bone healing. Thus, the development of biomaterials capable of regulating macrophage polarization to a favorable phenotype and promoting the synchronous regeneration of the tendon-to-bone interface is currently a top priority. Here, strontium-doped mesoporous bioglass nanoparticles (Sr-MBG) were synthesized through a modulated sol-gel method and Bi-lineage Inducible and Immunoregulatory Electrospun Fibers Scaffolds (BIIEFS) containing Sr-MBG were fabricated. The BIIEFS were biocompatible, showed sustained release of multiple types of bioactive ions, enhanced osteogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs), and facilitated macrophage polarization towards the M2 phenotype in vitro. The implantation of BIIEFS at the torn rotator cuff resulted in greater numbers of M2 macrophages and the synchronous regeneration of tendon, fibrocartilage, and bone at the tendon-to-bone interface, leading to a significant improvement in the biomechanical strength of the supraspinatus tendon-humerus complexes. Our research offers a feasible strategy to fabricate immunoregulatory and multi-lineage inducible electrospun fibers scaffolds incorporating bioglass nanoparticles for the regeneration of soft-to-hard tissue interfaces.

Nanofibers with homogeneous heparin distribution and protracted release profile for vascular tissue engineering.

In clinic, controlling acute coagulation after small-diameter vessel grafts transplantation is considered a primary problem. The combination of heparin with high anticoagulant efficiency and polyurethane fiber with good compliance is a good choice for vascular materials. However, blending water-soluble heparin with fat-soluble poly (ester-ether-urethane) urea elastomer (PEEUU) uniformly and preparing nanofibers tubular grafts with uniform morphology is a huge challenge. In this research, we have compounded PEEUU with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid PEEUU/heparin nanofibers tubular graft (H-PHNF) for replacing rats' abdominal aorta in situ for comprehensive performance evaluation. The in vitro results demonstrated that H-PHNF was of uniform microstructure, moderate wettability, matched mechanical properties, reliable cytocompatibility, and strongest ability to promote endothelial growth. Replacement of resected abdominal artery with the H-PHNF in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular smooth muscle cells (VSMCs) as well as stabilizing the blood microenvironment. This research demonstrates the H-PHNF with substantial patency, indicating their potential for vascular tissue engineering.

Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus.

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH-M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration.

Poly(ferulic acid)-hybrid nanofibers for reducing thrombosis and restraining intimal hyperplasia in vascular tissue engineering.

Small-diameter blood vascular transplantation failure is mainly caused by the vascular materials' unreliable hemocompatibility and histocompatibility and the unmatched mechanical properties, which will cause unstable blood flow. How to solve the problems of coagulation and intimal hyperplasia caused by the above factors is formidable in vascular replacement. In this work, we have synthesized poly(ferulic acid) (PFA) and prepared poly(ester-urethane)urea (PEUU)/silk fibroin (SF)/poly(ferulic acid) (PFA) hybrid nanofibers vascular graft (PSPG) by random electrospinning and post-double network bond crosslinking for process optimization. The results in vitro demonstrated that the graft is of significant anti-oxidation, matched mechanical properties, reliable cytocompatibility, and blood compatibility. Replacing resected rat abdominal aorta and rabbit carotid artery models with PSPG vascular grafts indicated that the grafts are capable of homogeneous hybrid PFA significantly promoted the stabilization of endothelial cells and the ingrowth of smooth muscle cells, meanwhile stabilizing the immune microenvironment. This research demonstrates the PSPG vascular graft with substantial patency, indicating their potential for injured vascular healing.

Corrigendum: Advances in regenerative sports medicine research.

[This corrects the article DOI: 10.3389/fbioe.2022.908751.].

Evaluation of electrospun PCL diol-based elastomer fibers as a beneficial matrix for vascular tissue engineering.

The main reason for the failure of artificial blood vessel transplantation is the lack of mechanically matched materials with excellent blood compatibility. The electrospun biodegradable polyurethane (BPU) fibers with micro to nanoscale topography and high porosity similar to the natural extracellular matrix (ECM) is one of the most suitable options for vascular graft. In our recent study, we prepared a series of PCL-based BPU fibers by combining two-step solution polymerization and electrospinning. SEM, 1H NMR, ATR-FTIR, XRD, TG, water contact angle, and mechanical tests were used to analyze the chemical structure, microstructure, thermal properties, surface wettability, degradation, cytocompatibility, and hemocompatibility in vitro of electrospun fibers. The results show that the synthesized H-PEUU, L-PEUU, H-PEEUU, and L-PEEUU have different crystalline properties, thus exhibiting distinctive thermal, mechanical, and degradation properties. Although the existence of the molecular structure of LDI and PEG600 in fibers can promote cell proliferation and migration unilaterally, the microstructure of the material is also the main factor affecting the biocompatibility of cells. The results suggest that the designed PCL-based degradable polyurethane electrospun fiber is expected to be applied to vascular tissue engineering.

A dZnONPs Enhanced Hybrid Injectable Photocrosslinked Hydrogel for Infected Wounds Treatment.

Chronic wounds caused by related diseases such as ischemia, diabetes, and venous stasis are often hard to manage, mainly because of their susceptibility to infection and the lack of healing-promoting growth factors. Functional hydrogel is a promising material for wound treatment due to its regulable swelling rate and its ability to absorb wound exudate, which can keep the wound isolated from the outside world to prevent infection. In this study, a photocrosslinked physicochemical double-network hydrogel with injectable, antibacterial, and excellent mechanical properties was prepared. The dZnONPs enhanced hybrid injectable photocrosslinked double-network hydrogel (Ebs@dZnONPs/HGT) was synthetized starting from acylated hyaluronic acid and tannic acid via free radical reaction and hydrogen bonding, following doped with ebselen (Ebs) loaded dendritic zinc oxide nanoparticles (dZnONPs) to prepare the Ebs@dZnONPs/HGT hydrogel. The physicochemical characterization confirmed that the Ebs@dZnONPs/HGT hydrogel had excellent mechanical properties, hydrophilicity, and injectable properties, and could fit irregular wounds well. In vitro experiments revealed that the Ebs@dZnONPs/HGT hydrogel presented credible cytocompatibility and prominent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vivo experiments further demonstrated that the Ebs@dZnONPs/HGT hydrogel had excellent biosafety and could improve re-epithelialization in the wound area, thus significantly accelerating wound healing.

Electrospun PCL/collagen hybrid nanofibrous tubular graft based on post-network bond processing for vascular substitute.

Inhibiting thrombus formation and intimal hyperplasia is essential for orthotopic tissue-engineered vascular grafts. The matching mechanical properties of autologous blood vessels and inhibition of platelet aggregation are considered as two points to improve the success rate of transplantation. The poly(ε-caprolactone)/collagen/heparin composite vascular graft (PCLHC) with three-dimensional network structure were constructed by electrospinning, which can mimic natural vascular biomechanics and enhance the viability of cells viability in vitro. The hybrid collagen matrix network nanofibers formed by electrospinning exhibited uniform and smooth morphology. The results of mechanical experiments showed that PCLHC had similar mechanical properties to natural blood vessels. And the addition of heparin enhanced the anticoagulation of PCLHC. Simultaneous three-component hybrid nanofibers showed a potentially reliable ability to promote the proliferation of human umbilical vein endothelial cells (HUVECs). In summary, all the results showed that the three-dimensional network structure of PCLHC presented the potential to heal injured vessels.

Advances in Regenerative Sports Medicine Research.

Regenerative sports medicine aims to address sports and aging-related conditions in the locomotor system using techniques that induce tissue regeneration. It also involves the treatment of meniscus and ligament injuries in the knee, Achilles' tendon ruptures, rotator cuff tears, and cartilage and bone defects in various joints, as well as the regeneration of tendon-bone and cartilage-bone interfaces. There has been considerable progress in this field in recent years, resulting in promising steps toward the development of improved treatments as well as the identification of conundrums that require further targeted research. In this review the regeneration techniques currently considered optimal for each area of regenerative sports medicine have been reviewed and the time required for feasible clinical translation has been assessed. This review also provides insights into the direction of future efforts to minimize the gap between basic research and clinical applications.

Crimped nanofiber scaffold mimicking tendon-to-bone interface for fatty-infiltrated massive rotator cuff repair.

Electrospun fibers, with proven ability to promote tissue regeneration, are widely being explored for rotator cuff repairing. However, without post treatment, the microstructure of the electrospun scaffold is vastly different from that of natural extracellular matrix (ECM). Moreover, during mechanical loading, the nanofibers slip that hampers the proliferation and differentiation of migrating stem cells. Here, electrospun nanofiber scaffolds, with crimped nanofibers and welded joints to biomimic the intricate natural microstructure of tendon-to-bone insertion, were prepared using poly(ester-urethane)urea and gelatin via electrospinning and double crosslinking by a multi-bonding network densification strategy. The crimped nanofiber scaffold (CNS) features bionic tensile stress and induces chondrogenic differentiation, laying credible basis for in vivo experimentation. After repairing a rabbit massive rotator cuff tear using a CNS for 3 months, the continuous translational tendon-to-bone interface was fully regenerated, and fatty infiltration was simultaneously inhibited. Instead of micro-CT, µCT was employed to visualize the integrity and intricateness of the three-dimensional microstructure of the CNS-induced-healed tendon-to-bone interface at an ultra-high resolution of less than 1 µm. This study sheds light on the correlation between nanofiber post treatment and massive rotator cuff repair and provides a general strategy for crimped nanofiber preparation and tendon-to-bone interface imaging characterization.