In recent years, some scholars have proposed the usage of ultrasonic scalpel in endoscopic transaxillary breast augmentation to achieve safer and more effective results. In order to compare electric cautery with ultrasonic scalpel on their effectiveness and safety in breast augmentation surgery, we performed a self-control study. From June 2022 to January 2025, a total of 45 cases of transaxillary endoscopic breast augmentation surgery were included in the study. All cases were performed by dual-plane technique. Drainage volume, surgical time, postoperative complications were compared and evaluated on both sides. The total postoperative drainage volume in the electric cautery group and the ultrasonic scalpel group was as follows: 268.3±130.0 ml and 274.7±141.7 ml. The average number of drainage days was 4.2±0.9 days. The surgical time for the electric cautery (13.8±2.9 min) was shorter than that for ultrasonic scalpel (15.6±3.4 min). There is no significant difference between the use of electric cautery and ultrasonic scalpel in endoscopic breast augmentation surgery in terms of reducing postoperative bleeding, shortening drainage time, and hospital stay. There are no advantages to perform the endoscopic transaxillary breast augmentation surgery with the usage of ultrasonic scalpel, and even the operation time may be extended. 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 .
Conventional magnetic assembly strategies for hydrogel constructs face fundamental limitations in achieving multiscale structure construction due to transient magnetic response and lack of magnetic domain programming. We present a hierarchical assembly strategy utilizing magnetic memory liquid droplets as guidable building blocks for heterogeneous hydrogel structures. Through interfacial jamming of alginate-surfactant membranes and subsequent photo-crosslinking, we engineer ferromagnetic liquid droplets containing polyethylene glycol (PEG)-modified iron oxide nanoparticles that exhibit magnetic memory. These units enable hierarchical assembly via sequential magnetization and re-magnetization cycles. The molded building block can be reconfigured using induction magnetic dipoles, which determine the building block's magnetic assembly and actuation behavior. Meanwhile, by adjusting the intensity and direction of the external magnetic field, the assembly can perform directional delivery in narrow and tortuous spaces. These biocompatible, complex, and multifunctional hydrogel assemblies can be readily applied to tissue engineering, regenerative medicine, and biomimetics. STATEMENT OF SIGNIFICANCE: Fabricating complex, biocompatible hydrogels with spatial control remains a challenge in tissue engineering. Conventional magnetic assembly methods are limited by transient magnetic responses and lack programmable domain control, hindering multiscale heterogeneous structure formation. This work presents a hierarchical magnetic assembly strategy using magnetized liquid droplets with magnetic memory, enabling heterogeneous hydrogel construction through magnetization-remagnetization cycles, actuation, and reconfiguration under external fields. The strategy's effectiveness is demonstrated by fabricating a blood vessel tissue mimic.
To develop and validate a cartilage organoid (CO)-laden digital light processing (DLP) bioprinting strategy for auricular reconstruction and to compare its performance with conventional chondrocyte-laden prints. Rat bone-marrow stromal cells (BMSCs) were aggregated into spheroid and chondrogenically induced to form CO. Organoid construction and characterization included EdU proliferation assay, CD73/CD90 immunofluorescence (IF), and real-time quantitative polymerase chain reaction (qPCR) of chondrogenic genes. O-nitrobenzyl functionalized gelatin (GelNB)/ methacrylated hyaluronic acid (HAMA) bioinks were screened by gross morphology, tensile/ compressive mechanics, enzymatic degradability (0.1
Breast reconstruction is essential for restoring self-image and quality of life after mastectomy. While current methods using implants or autologous tissue are prevalent, they face challenges such as capsular contracture and volume loss. This review explores how bio-fabrication strategies are generating innovative scaffolds to overcome these limitations. We discuss the clinical use of bio-fabrication and detail preclinical progress in key areas: enhancing the biocompatibility and safety of implants, achieving soft tissue regeneration and vascularization, integrating antitumor therapy with reconstruction, and optimizing aesthetic outcomes. Finally, we outline future research directions for developing superior biomaterials to advance breast reconstruction. Statement of Significance Current breast reconstruction methods are limited by complications, such as capsular contracture, volume loss, and infection. This review underscores the promise of bioengineered scaffolds, where biomaterials combined with bioactive agents and advanced fabrication (e.g., 3D printing) can recreate the natural breast microenvironment to support regeneration. This replication is crucial for promoting vascularization, adipogenesis, and tissue integration. Furthermore, we explore new strategies for modifying implant surfaces to minimize fibrosis and infection risks. This work serves as a guide for developing next-generation regenerative scaffolds and highlights their potential to significantly improve clinical outcomes in breast reconstruction by providing personalized, biocompatible, and functionally' as none of the work so far in the literature can truly replicate the natural breast microenvironment.
BACKGROUND:Masseter muscle prominence (MMP) may be aesthetically bothersome to some individuals, leading them to seek treatment for a slimmer lower face. OBJECTIVES:The aim of this study was to evaluate the safety and efficacy of onabotulinumtoxinA for the treatment of MMP, including patient-reported outcomes (PROs). METHODS:This was a prospective, multicenter trial including a randomized, double-blind, placebo-controlled period (Days 1-180) in which adults rated Grade 4 or 5 (marked/very marked) on the investigator-assessed MMP Scale (MMPS) were randomized to onabotulinumtoxinA 72 U or placebo. Efficacy endpoints were assessed at Day 90. The primary endpoint was ≥2-grade improvement from baseline on the investigator-assessed MMPS. Secondary endpoints included achieving Grade ≤3 on the MMPS and participant-assessed MMPS-Participant (MMPS-P), ≥2-grade improvement on the participant-assessed MMPS-P, and change from baseline in lower-facial width. Outcomes were assessed using validated measures. Adverse events (AEs) were monitored. RESULTS:Of 376 enrolled participants (onabotulinumtoxinA, n = 283; placebo, n = 93), 310 (82.4%) completed the study. At Day 90, a greater proportion of onabotulinumtoxinA-treated participants vs placebo achieved MMPS ≥2-grade improvement (51.2% vs 2.2%, P < .0001), and more onabotulinumtoxinA-treated participants vs placebo achieved the secondary endpoints (all P < .0001), with a mean lower-facial width reduction of -5.24 mm for onabotulinumtoxinA vs -0.04 mm for placebo (P < .0001). Participants reported benefits for onabotulinumtoxinA vs placebo in self-perceived change in MMP, treatment satisfaction, and psychosocial impact. Improvements were sustained through Day 180. Most AEs were mild, nonserious, and resolved. CONCLUSIONS:OnabotulinumtoxinA effectively reduced the appearance of MMP and improved PROs, with effects lasting up to 6 months and a favorable safety profile. LEVEL OF EVIDENCE: 1 (THERAPEUTIC):
Exosome-mediated tissue-tissue communication represents a fundamental mechanism that maintains physiological homeostasis. This study proposes a novel therapeutic approach based on liver-bone cross-talk, wherein hepatocyte-derived exosomes (h-EXOs) markedly accelerated the repair of critical cranial defects. Specifically, h-EXOs were anchored onto a digital light processing (DLP)-printed scaffold (PH/PDA) composed of polycaprolactone macromolecule polymer (PCLMA) and nano-hydroxyapatite (nHap) via a polydopamine (PDA) coating to promote cranial bone regeneration. These PH/PDA scaffolds substantially enhanced bone mesenchymal stem cells (BMSCs) adhesion and proliferation, while the incorporated h-EXOs significantly promoted angiogenesis and osteogenic differentiation. Moreover, RNA sequencing revealed that h-EXOs were enriched in cargoes governing diverse cellular processes and activated the PI3K/AKT pathway to promote BMSCs osteogenesis. Following implantation, PH/PDA/h-EXOs scaffolds induced substantial defect closure and fostered a regenerative microenvironment similar to native calvarial tissue, characterized by an expansion of anti-inflammatory M2 macrophages and osteoblasts alongside pronounced vascularization. Overall, this study leverages inter-organ crosstalk in conjunction with personalized scaffold fabrication to propose a novel tissue-engineering strategy for enhancing tissue repair.
BACKGROUND:Capsular contracture (CC) remains one of the most common complications following breast implant surgery, yet its underlying mechanisms are not fully clarified. The mechanosensitive ion channel Piezo1 has been implicated in fibrotic processes across various organs; however, its role in breast implant-associated fibrosis remains unknown. OBJECTIVE:This study aimed to investigate the expression and functional significance of Piezo1 in the pathogenesis of breast implant-associated capsular contracture. METHODS:Using a murine silicone-implanted model, we analyzed expression of Piezo1 during capsule formation. Human capsular tissues (normal and contracted) were examined for Piezo1 expression. A lipoteichoic acid (LTA)-induced contracture model was employed to assess the therapeutic effect of GsMTx4, a specific Piezo1 inhibitor. Evaluations included histology, immunofluorescence, and Western blot analysis. RESULTS:Piezo1 expression was significantly upregulated during early capsule formation in mice, showing a correlating with collagen deposition and capsular thickening. Patients contracted capsules exhibited markedly higher Piezo1 levels compared to normal capsules. In the LTA-induced contracture model, pharmacological inhibition of Piezo1 with GsMTx4 substantially reduced collagen deposition, capsular thickness, and Piezo1 expression levels. CONCLUSION:Our findings establish Piezo1 as a critical mediator in the pathogenesis of breast implant-associated capsular contracture. The channel's dynamic expression and the efficacy of its inhibition highlight its pivotal role in the fibrotic process. Piezo1 represents a novel target, offering a promising therapeutic strategy for preventing this challenging complication. LEVEL OF EVIDENCE V: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 .
Skin fibrosis substantially contributes to morbidity and mortality. Fibrotic remodeling, characterized by accumulated and stiffened extracellular matrix, persistently exerts mechanical cues and consistently activates fibroblasts, implying biomechanics as a major driver of fibrosis. However, our understanding towards mechanisms of biomechanics induced fibrosis remained limited. Integrated single-cell sequencing analysis was performed to reveal the atlas of fibrotic skin. ChIP sequencing was performed to reveal the binding sites of CREB3L1. Nanoindenter was used to identify the mechanical properties. Gel contraction assay, wound healing assay, and live cell imaging were conducted to assess the behavior of fibroblasts cultured on hydrogels of different rigidities. Bleomycin induced and mechanical loading induced skin fibrosis models were established on CREB3L1 knockdown and control mice. We identified a mechanosensitive fibroblast cluster that exerts contraction and ECM deposition functions in fibrotic skin, and its transcriptional identity was maintained by CREB3L1. Elevated expression of CREB3L1 was confirmed in human and mouse fibrotic skin. Further analysis showed that CREB3L1 was required for fibroblast activation, including contraction, migration, and ECM accumulation. More importantly, we revealed that matrix stiffness could alter calcium homeostasis, causing calcium influx and endoplasmic reticulum stress. The ER stress state in turn triggered the cleavage of CREB3L1, releasing its luminal domain that function as a profibrotic transcription factor. Inhibiting CREB3L1 could alleviate skin fibrosis both in vivo and in vitro. This study elucidates the molecular mechanism of CREB3L1 mechanosensitive activation in matrix stiffness induced skin fibrosis, and presents a promising therapeutic target for clinical translation.
Visible anterior neck scars after thyroidectomy and related cervicotomy procedures remain clinically important aesthetic and psychosocial concerns. This systematic review and network meta-analysis compared randomized evidence for early scar-directed interventions, while separating surgical closure method trials from postoperative scar modulation strategies. PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched independently from database inception to 17 June 2026. The primary outcome was scar quality at the longest available 3- to 12-month follow-up, assessed using POSAS, OSAS/PSAS, VSS/mVSS, SBSES, and MSS in a prespecified hierarchy. The primary connected network included six randomized trials comprising 408 unique participants and 469 analyzed scar/incision observations, with 10 direct comparisons and eight scar-directed treatment nodes. Laser plus steroid demonstrated a favorable low-certainty network estimate (standardized mean difference (SMD) −1.35, 95% CI −1.87 to −0.83), as did laser/light-based protocols (SMD −0.95, 95% CI −1.40 to −0.50). Platelet-rich plasma also showed a favorable estimate (SMD −0.95, 95% CI −1.73 to −0.16), but this evidence was very uncertain because the node was supported by a single small study with methodological concerns. CINeMA certainty was low or very low across comparisons. Closure method trials were retained as a descriptive evidence map because their mechanisms, timing, and clinical decision context differed from scar-directed therapy. These findings should be interpreted as hypothesis-generating and do not support definitive comparative superiority claims.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261427171, PROSPERO CRD420261427171.
The skin is a three-dimensional organ composed of multilayered tissues, in which the epidermis, dermis, and subcutaneous adipose layer cooperate to maintain protection, thermoregulation, and repair. Although recent advances in tissue-engineered skin substitutes have improved cutaneous regeneration, strategies that simultaneously promote dermal and adipose restoration remain limited. Here, we developed a bi-layered tissue-engineered skin scaffold with dermal-adipose architecture fabricated by conjugate electrospinning of polycaprolactone solutions containing acellular dermal matrix (ADM) or decellularized adipose tissue (DAT). The construct exhibited dual bioactivity: stimulating fibroblast proliferation and collagen remodeling in the dermal layer, while promoting adipose-derived stem cell proliferation and adipogenesis in the adipose layer. In a full-thickness nude rat wound model, the scaffold enhanced vascularization, modulated inflammation, and accelerated regeneration of both dermal and adipose tissues. These findings demonstrate a versatile platform for multilayered skin tissue engineering and provide new insight into dermal-adipose synergistic regeneration.
Despite advancements in bio-manufacturing, the fabrication of large-scale vascularized tissue with heterogeneous cells remains a daunting challenge. To address this challenge, the reverse engineered structured tissue (REST) three-dimensional (3D) bioprinting method was proposed. This strategy enables the seeding and subsequent assembly of multiple tissue-specific constituent cells onto a robust, flexible, 3D biomimetic vascular scaffold with long-term perfusion capability. The material choices for the vessel network and seeding cells could be decoupled, and separate co-culture of multiple seeding cells in a customized bioreactor could be realized. The cellular layers could be reassembled into an engineered tissue by manually folding the robust vessels. Centimeter-scale vascularized skin-flap-like tissues that comprise epidermal, dermal, and adipose layers were engineered with an in vivo-like communicating vascular network using this strategy. The engineered tissue exhibits three-layered cellular heterogeneity (containing HaCaT cells, fibroblasts, and adipose-derived stem cells) and perfusable tubes (containing HUVECs and VSMCs). The complex tissue could be remolded through in vitro perfusion of vessel network and specific culture/differentiation medium supplied to tissue-specific cellular layers. After in vivo transplantation for three months, the tissue construct formed a viable complex tissue with a rich network of blood vessels. Our results demonstrate that "REST" bioprinting technology can be used to fabricate multicellular tissues, ranging from millimeter to centimeter scales with perfusable vessels, opening new avenues for functional artificial organ bioprinting.
Organoids have emerged as a powerful strategy to recapitulate tissue architecture and function, opening new avenues for regenerative medicine. However, clinical translation is hindered by limited control over the assembly of heterogeneous organoid units and the resulting loss of spatial organization at the tissue scale. In addition, macroscale organoid constructs face diffusion-limited oxygen and nutrient transport, leading to central necrosis. The poor vascular integration can hinder the further development and maturation of the organoids, ultimately preventing functional integration. To address these limitations, we developed Neo-Organoid Visualization and Assembly (NOVA), a living assembly strategy that integrates bioprinting with hydrogel-based bio-adhesive assembly to enable high-throughput modular assembly of bone organoids. Using this strategy, we generate a tissue-scale tubular bone organoid graft formed with in situ unidirectional guided vascularization. This structure enables the spatiotemporal coupling of angiogenesis and osteogenesis, enhances the maturation and function of bone organoids, and holds potential for one-step surgical transplantation with rapid perfusion to repair defects.
Extracellular vesicles (EVs) mediate communication between immune and stromal cells during cutaneous repair by transferring proteins, lipids, nucleic acids, and other bioactive components. This review examines their effects on macrophage inflammatory and stress-adaptation programs, fibroblast activation and fate, and macrophage–fibroblast crosstalk in wound healing and pathological scarring. In chronic and metabolically impaired wounds, stem- and stromal-cell EVs commonly reduce persistent inflammation, improve macrophage autophagy and redox balance, and support fibroblast migration, proliferation, survival, and provisional matrix formation. In scar models, some EV preparations attenuate sustained profibrotic and mechanotransduction signaling, whereas EVs from diseased or microenvironmentally conditioned cells can prolong inflammation, maintain myofibroblast activity, and increase collagen deposition. Direct evidence for EV-mediated crosstalk is less extensive than evidence for effects on either cell type alone but supports communication in both directions. Macrophage-derived EVs alter fibroblast metabolism, growth signaling, autophagy, and extracellular matrix (ECM) production through long noncoding RNAs, microRNAs, and chemokines. Fibroblast-derived EVs can coordinate phase-specific macrophage responses during repair, whereas EVs from diabetic ulcers or fibrotic skin may impair macrophage autophagy, activate inflammasome signaling, and reinforce profibrotic feedback. EV activity therefore depends on the state of both donor and recipient cells, the local matrix and metabolic environment, dose, and timing. Particular emphasis is placed on reciprocal EV-mediated macrophage–fibroblast signaling, an aspect of cutaneous repair that remains insufficiently synthesized despite increasing mechanistic evidence. Clinical translation will require causal validation of EV transfer, standardized product characterization, and long-term assessment of wound closure and scar quality.
Pathological scarring imposes a substantial global healthcare burden, affecting over 100 million individuals annually with costs exceeding $20 billion. Current therapies yield suboptimal outcomes due to limited efficacy and recurrence. Hydrogel‐based wound dressings have emerged as transformative platforms due to their tunable physicochemical properties, bioactivity, and ability to modulate the wound microenvironment. This review uniquely integrates scar biology with hydrogel‐based therapeutic strategies. A phase‐specific framework that correlates hydrogel functions is provided with key scar‐influencing events, including inflammation regulation, fibroblast reprograming, extracellular matrix remodeling, and skin appendage regeneration. Moreover, cutting‐edge innovations are highlighted such as stimuli‐responsive hydrogels (pH/temperature/light), nanocomposite systems, and 3D‐printed scaffolds that enable spatiotemporal control of drug release and dynamic microenvironment modulation. Furthermore, unresolved clinical translation barriers are critically addressed, including scalability, standardization, biocompatibility, and immune response variability, proposing interdisciplinary solutions. By synthesizing recent advances and persistent limitations, this work provides a translational roadmap for developing next‐generation hydrogels to bridge the gap between benchtop innovation and clinical scar‐free tissue regeneration.
BACKGROUND:Conventional botulinum toxin type A (BoNT/A) products include non-therapeutic accessory proteins vary in composition and manufacturing processes, which may contribute to differences in purity and biochemical characteristics. YY001 (Retoxin®) is a novel recombinant BoNT/A manufactured via E. coli expression to reduce impurities, improve purity, and minimize immunogenic risk. OBJECTIVES:To evaluate the efficacy, safety, and immunogenicity of YY001, a recombinant botulinum toxin type A (Chongqing Claruvis Pharmaceutical Co., Ltd., Chongqing, China), in the treatment of moderate-to-severe glabellar lines. METHODS:In this multicenter, randomized, double-blind, vehicle- and active-controlled Phase III trial, 529 adults aged 18-65 with moderate to severe glabellar lines were randomized 4:2:1 to receive a single 20 U injection of YY001, Botox®(Allergan Pharmaceuticals Ireland, Westport, Ireland), or vehicle. The primary endpoint was composite response rate (CRR) at Week 4, defined as a ≥2-grade improvement of glabellar line severity assessed by both investigator and participant. Secondary endpoints included onset time, duration, satisfaction, and safety. RESULTS:YY001 achieved a CRR of 86.7% at Week 4, significantly outperforming Botox® (66.7%, P < .0001) and vehicle (1.3%, P < .0001). It showed faster onset, longer median duration (97 days), and high participant satisfaction. Adverse events were mild and comparable across groups. Only one case of anti-drug antibody was observed; no neutralizing antibodies were detected. A 12-week follow-up and ethnically homogenous population may limit generalizability. CONCLUSIONS:YY001 demonstrated strong efficacy and a favorable safety profile than Botox®. Longer-term and multicenter studies are needed to assess durability, immunogenicity, and applicability across broader populations. LEVEL OF EVIDENCE: 1 (THERAPEUTIC):For image description, please refer to the figure legend and surrounding text.
Reconstructing biomechanical hierarchy and vascularization in heterogeneous tissues is critical for effective repair. Achieving this requires integrating materials with distinct mechanical properties. To address this, we develop a hybrid fabrication strategy-Hybrid Fabrication of Stiffness-Flexible Integration (HFSF). This strategy enables the engineering bone scaffolds with both mechanical hierarchy and perfusable vasculature. The outer layer (ZP scaffold), mimicking cortical bone, is made using zeolitic imidazolate framework-8/polycaprolactone (ZIF-8/PCL) through fused deposition modeling (FDM). In vitro mineralization enhances its mechanical strength and osteogenic-angiogenic potential. A robust hydrogel (PH scaffold) mimicking cancellous bone is synthesized from o-nitrobenzyl alcohol-terminated tetra-armed polyethylene glycol/hyaluronic acid (PEGNB/HAMA) and fabricated via digital light processing (DLP) printing. The PH scaffold incorporates intricate vascular channels. In vitro culture with endothelial cell seeding upregulates endothelial gene expression and promotes angiogenesis. The ZPPH scaffold demonstrates excellent protection of internal structures, robust vascularization, and bone formation in both in vitro and in vivo models. This innovative “structure-mechanics-biology” strategy offers a promising approach for engineering vascularized, mechanically hierarchical scaffolds for heterogeneous tissue repair.
Hydrogel scaffolds play a crucial role in tissue engineering; however, traditional bulk hydrogel scaffolds (BHS) often suffer from insufficiently sized pores (nanoscales), impeding cellular infiltration, development, and expansion. This limitation affects oxygen and nutrient exchange efficiency, in which case it relies extensively on liquid permeation and bulk hydrogels swelling. In contrast, hydrogel microparticles (HMPs) have proven to be both printable and injectable, allowing the development of modular thick constructs with interconnected pores. This study introduces a novel method of fabricating porous granular hydrogel scaffolds (GHS) by printing thermo-crosslinked gelatin methacryloyl (GelMA) HMPs granular hydrogels before chemical crosslinking (dual-crosslinking). The scaffolds exhibit an average pore fraction ranging from 14 % to 23 % and an average pore size varying from 4923 μm2 to 8185 μm2 (with equivalent circular diameter of 80-102 μm). In vitro experiments demonstrated the effective infiltration, adhesion, proliferation, and adipogenic differentiation of human adipose-derived stem cells (hADSCs) within the scaffold pores. Additionally, in vivo observations confirmed the presence of differentiated adipose cells within the central pores after 4 weeks. These results collectively suggest the proposed microspheres printing technique holds significant promise for fabricating microporous scaffolds and further applications in tissue engineering.
The stromal vascular fraction (SVF) has been validated for enhancing tissue regeneration because of its concentration of multipotent cells and growth factors, and for mitigating inflammatory response due to its elimination of the majority of lipid droplets. However, it is difficult for fresh SVF to maintain bioactivity for a long period, and the loss of numerous tangible masses during preparation limits its application in repairing large volume defects. Here, we fabricated a self-assembly nanovesicle extruded from SVF (SVF-EVs) by mechanical shear and co-transplanted it with dermal microparticles to verify its potential for repairing large volume defects. The SVF-EVs were prepared by removing the oil from adipose tissue followed by sequentially extruding SVF through membrane filters. The lipid content of SVF-EVs was compared with SVF using Oil Red O staining. The morphology and adipogenic-related protein of SVF-EVs were characterized. The pro-adipogenic potency of SVF-EVs in vitro was determined using Oil Red O staining of ADSCs, western blot, and qRT-PCR. In vivo, dermal particle grafts mixed with SVF-EVs were subcutaneously transplanted in nude mice and harvested after 4 and 6 weeks. By examining the weight and volume of grafts and histological staining, we explored the effect of SVF-EVs on adipose tissue regeneration and anti-inflammatory ability. Our results showed that the removal rate of proceeding of SVF-EVs could remove 75.07 ± 2.80
Reconstructing the hierarchical structure and blood perfusion capacity of bone tissue is essential in bone repair. However, when engineering vascularized bone mimicking scaffolds, it remains challenging to integrate a vascular system, a hierarchical bone structure for promoting bone tissue regeneration. We herein designed a Haversian bone mimicking OsteoChip scaffold that has a multilayer, perfusable microchannel network to support endothelial cell coating, as well as a cancellous bone-mimicking structure that supports the growth of bone marrow mesenchymal stem cells (BMSCs). The OsteoChip scaffold is fabricated by 3D stamping of poly (octamethylene maleate (anhydride) citrate) (POMaC) and nano-hydroxyapatite (nHap), endowing it with enhanced mechanical strength and osteogenesis activity that supports dynamic multicellular culture in vitro and direct surgical anastomosis upon implantation. We also show that vascularized bone grafts developed using OsteoChip scaffold exhibited obvious angiogenesis and osteogenesis both in vitro and in vivo. The OsteoChip accelerates the development of biomimetic, perfusable vascularized bone grafts which greatly broadens the clinical application prospects of bone tissue engineering.