Objectives To present a robot-assisted protocol for autogenous mandibular molar transplantation using an autonomous robotic system for shape-matched recipient socket preparation. Methods The novel workflow comprises the following steps: 1) Preoperative planning: Based on preoperative intraoral scans and cone-beam computed tomography (CBCT) data, the transplant position of the donor tooth was precisely planned, and the surgical path was generated. An intraoral registration device was designed and fabricated, and a donor tooth replica was 3D-printed. 2) Intraoperative execution: Following the preoperative plan, the robot performed supervised autonomous, layer-by-layer, incremental milling to prepare a personalized osteotomy socket that accurately matched the donor root morphology. All remaining surgical steps were completed by the surgeon. 3) Post-operative evaluation: Intraoperative post-operative CBCT was acquired for accuracy analysis and assessment. Results The procedure was completed successfully, with no intra- or post-operative complications reported. All positional and angular deviations of the transplanted tooth fell within clinically acceptable limits. Conclusions A workflow for tooth autotransplantation using an autonomous robotic system was successfully implemented, preliminarily demonstrating its ability to achieve accurate morphologically matched socket preparation. Clinical significance This study proposes and validates a complete digital and robot-assisted method for socket preparation in autotransplantation, offering a novel technical pathway toward personalized, high-precision tooth transplantation. The approach holds promise for improving procedural predictability and standardization; however, its clinical benefits require further validation through larger controlled studies.
Wound healing requires a timely transition from inflammation to proliferation, yet chronic wounds often stall in prolonged inflammation. An unresolved question is how physical cues in injured tissue influence macrophages to orchestrate this transition. Here, we find that loss of cytoskeleton-associated protein 4 (CKAP4) in macrophages accelerates wound closure and inflammation resolution in mice. CKAP4-deficient wounds exit the inflammatory state earlier, show higher expression of reparative genes, and promote faster angiogenesis and tissue regrowth. Mechanistically, CKAP4 binds Talin1 to restrain adhesion-associated signaling and STAT6 nuclear translocation. Its deficiency heightens macrophage sensitivity to matrix stiffness, triggering cytoskeletal remodeling and a pro-regenerative program at lower stiffness thresholds. In a diabetic wound model, local silencing of Ckap4 in macrophages restores their mechanoresponsiveness, advances the inflammation-to-proliferation transition, and improves healing. Thus, CKAP4 acts as a negative regulator of macrophage mechanosensing, and targeting this pathway offers a mechanotherapeutic avenue for wound treatment.
This study evaluated the influence of print angle and layer thickness on the accuracy and fit of resin-based ceramic crowns fabricated using digital light processing (DLP). A mandibular first molar crown was virtually designed and then printed at two layer thicknesses (50 μm and 100 μm) and nine print angles (90°–270°). Accuracy was assessed by trueness, precision, and surface-resolved deviation metrics using 3D deviation analysis, whereas fit was evaluated with the triple-scan method. Both print angle and layer thickness significantly affected accuracy and fit (P < 0.001). Trueness and fit values showed a nonlinear trend across print angles, with optimal results consistently observed at moderate inclinations of 150°–180°. Crowns printed at 50 μm showed better trueness and fit, whereas those printed at 100 μm showed more concentrated deviation distributions. Surface-resolved metrics revealed negative deviations at the marginal surfaces and positive deviations at the occlusal surfaces. Although all crowns showed clinically acceptable fit (<120 μm), the results indicate that a moderate print angle of 150°–180° combined with a 50 μm layer thickness provides the best balance between accuracy and clinical fit, while a 100 μm layer thickness may be preferable when printing consistency is prioritized.
OBJECTIVES:To develop a robotic system for full crown tooth preparation and to evaluate its preparation accuracy and operation time. METHODS:The robotic system comprised a robotic arm, an infrared optical tracking system, and proprietary planning/control software. The planning workflow encompassed path planning for axial and occlusal surfaces, functional cusp bevels, and acute line angles, culminating in the generation of an ideal preparation morphology. Twenty-two standardized partial dentition models of mandibular teeth 35-37 were additively manufactured and equally allocated into two experimental groups based on preparation methodology: an automated robotic system group and a step-by-step guide group. Operation time was recorded concurrently. Post-preparation scan data were imported into three-dimensional reverse engineering software to calculate the root-mean-square-error (RMSE) values for the overall surfaces, axial surfaces, occlusal surfaces, and chamfer regions to evaluate preparation accuracy. RESULTS:In the posterior crown preparation model experiment, the robotic group showed significantly lower RMSE values than the guide group overall and by region: overall, 0.18±0.03 vs 0.33±0.05 mm; axial, 0.15±0.06 vs 0.27±0.08 mm; occlusal, 0.20±0.05 vs 0.38±0.07 mm; chamfer, 0.12±0.03 vs 0.30±0.07 mm. The occlusal surface yielded the lowest accuracy in both groups. The robotic system also significantly reduced preparation time (350.15±7.79 s vs. 583.93±90.48 s), confirming its efficiency advantage. CONCLUSIONS:This study developed an automated robotic system for crown preparation that demonstrated superior accuracy and shorter operation time compared with the guide approach. CLINICAL SIGNIFICANCE:In this study, we developed a novel robotic system for full crown preparation that may enable precise and efficient procedures, representing a promising approach for achieving high-accuracy tooth preparation while minimizing tissue removal.
Segmental tracheal reconstruction requires biomimetic substitutes that replicate both the rigid stenting of cartilage rings and the nutritional support of vascularized fascia. However, conventional tissue engineering is hampered by scarce donor chondrocytes and lengthy cell expansion. Here, we show a rapid tracheal reconstruction strategy using three-dimensional printed porous minichannel scaffolds filled with cartilage granules, platelet-rich plasma, and adipose-derived stem cells. Short-term ectopic incubation enables the grafts to acquire native-like mechanical resilience and transmural vascularization within two weeks. Upon orthotopic transplantation to repair segmental tracheal defects in rabbit and porcine models, these bioengineered grafts maintain airway patency and support preclinical animal survival for up to 115 days. Mechanistically, adipose-derived stem cells enhance cartilage granule survival within the hypoxic minichannels by upregulating glycolytic activity in chondrocytes. By eliminating the need for cell isolation and expansion, this approach offers a translatable solution for bioengineered airway repair. There, the authors develop a tracheal reconstruction strategy using 3D-printed minichannels with stem cell–cartilage composites in preclinical models. Bypassing cell expansion, these tough grafts achieve rapid vascularization and repair segmental airway defects.
PURPOSE:Extensive maxillectomy may result in rapid contour changes in the unsupported facial tissue, causing irreversible and severe aesthetic deformities. This technical report details a novel digital workflow for the fabrication of obturators with immediate facial support consistent with the existing maxillary contour. METHODS:Preoperative digital impressions were obtained using an intraoral scanner (IOS). A three-dimensional (3D) model of the presurgical maxillofacial hard tissue was constructed using cone-beam computed tomography (CBCT) and aligned with the IOS data. Surgical planning data were used to guide the separation and fusion of anatomical reference data for obturator design from the CBCT and IOS data. The obturator was designed using dental design software, and the existing maxillary morphology for facial support was transferred to the obturator. After the surgical resection, an immediate obturator with a surgical pack was placed at the defect site. CONCLUSIONS:The implementation of a fully digital workflow demonstrated the potential to streamline the complex procedure traditionally required to restore harmonious facial contour support through the transfer of maxillary morphology to the immediate obturator. This method offers a promising and viable alternative to conventional techniques, with the potential to minimize long-term aesthetic compromise, facilitate adaptation and functional restoration, and simplify postoperative prosthetic care.
Crown preparation aims to create an optimal foundation for durable and functional restoration by reshaping the tooth with a cutting tool. Robotic crown preparation has emerged as a promising approach to overcome the inherent limitations of manual procedures, yet challenges remain in achieving efficient cutting path generation, collision-free orientation adjustment and precise cutting path following, since the oral cavity is a confined space with the target tooth tightly surrounded by other teeth. This paper introduces a novel, in-situ automated robotic full crown preparation system comprising (1) Preoperative Path Planning: generating high-efficiency universal cutting paths based on tooth morphological features; (2) Intraoral Collision Avoidance: optimizing the cutting tool's orientation within the constrained oral cavity; (3) MPC-Based Adaptive Control: modulating the path-following feed rate using model predictive control (MPC) according to intraoperative force feedback. The proposed system was thoroughly validated on a human head phantom targeting a permanent tooth to simulate a real clinical scenario, yielding an average root-mean-square (RMS) error (tooth shape after preparation) of 0.17 mm and an overall mean execution time of 347.77 s, achieving a 74.2% improvement in cutting efficiency over state-of-the-art methods. A comparative evaluation against conventional dental guides further demonstrates its technical feasibility and significant potential for clinical translation.
Tooth autotransplantation requires recipient socket preparation that matches donor root morphology while preserving surrounding bone. We developed an autonomous multi-axis robotic system that executes nonlinear, surface-conforming milling trajectories to create a geometry-matched socket and compared it with a static tooth-supported guide in forty 3D-printed mandibular models representing single-rooted and double-rooted anatomies. Recipient sockets were planned by offsetting the donor root surface by 0.5 mm and eliminating insertion axis undercuts. The robot executed the planned milling path with a depth-stop Lindemann bur, whereas the guide workflow used guided pilot drilling followed by freehand refinement. Robot assistance reduced deep positional errors and improved agreement between planned and prepared socket geometry, with the most pronounced benefit in double-rooted models, while overall preparation time was comparable between approaches. These findings support further clinical validation to confirm that autonomous robotic, surface-conforming osteotomy can improve full-depth geometric fidelity and reduce unnecessary bone removal in technique-sensitive autotransplantation procedures.
ABSTRACT Objectives This retrospective, non‐interventional study aimed to evaluate the longevity and factors influencing the success of custom‐fabricated polyetheretherketone (PEEK) post‐and‐cores in endodontically treated teeth (ETT). Material and Methods During the observation period (2019–2022), 63 patients received 100 customized PEEK post‐and‐cores. Clinical outcomes were analyzed based on the following parameters: age, gender, tooth type, tooth position, proximal contacts, remaining cavity walls, antagonist contacts, and final restoration. Kaplan–Meier analysis was used for the survival probability. Log‐rank tests were used to identify univariate associations between failure rates and other potential factors. Cox regression was used to assess the risk of failure and determine possible risks between the identified factors at a cut‐off point p‐value (0.25 in univariate analysis). Results The median follow‐up duration was 20.62 months, with a maximum of 40.57 months. 93 restorations were judged as successful and 99 teeth survived. The main failure type was decementation of the restoration (n = 4). The annual failure rate was 3.4%. Gender, remaining tooth structure, and final restoration were found to be correlated with success rates in the preliminary univariate analysis (Log‐rank tests) to determine the association between failure rates and potential factors. Multifactorial survival analysis (Cox regression) showed that teeth with coronal walls had a significantly lower failure risk than deprived teeth, even with the ferrule effect. (HR = 0.04; 95% CI for HR = 0.01–0.29; p = 0.002). Conclusions PEEK post‐and‐cores adapt well to clinical restorative needs and offer favorable short‐term clinical outcomes. The remaining cavity wall was a significant success rate predictor.
BackgroundManagement of compound odontomas in the pediatric anterior mandible poses significant surgical challenges due to proximity to developing tooth follicles and neurovascular structures. Conventional enucleation risks iatrogenic injury to adjacent dentoalveolar anatomy, while suboptimal bone preservation may impede permanent tooth eruption.Case descriptionAn 8-year-old patient presented with a compound odontoma adjacent to the unerupted permanent mandibular incisor. Utilizing an autonomous robotic guidance system independently developed by our research group, we performed minimally invasive enucleation featuring: (1) virtual osteotomy pathway planning, (2) sub-millimeter precision bone removal preserving the follicular space of tooth 31, and (3) capsule dissection under optical navigation. At the 2-week follow-up, the surgical site demonstrated complete mucosal healing without neurosensory complications, and CBCT confirmed absence of residual pathology.ConclusionRobotic-assisted enucleation enabled tissue-preserving removal of a high-risk odontoma while maintaining eruption potential. This approach represents a paradigm shift toward precision-targeted dentoalveoral surgery, particularly valuable for anatomically complex pediatric cases.Clinical Trial Registrationidentifier [ChiCTR2400092822].
To evaluate the clinical efficacy of an autonomous robotic system in reducing bone resection volume and operative time for impacted teeth extraction in children, compared to conventional surgical techniques. A single-blinded randomized controlled trial enrolled 10 pediatric patients impacted teeth. Each participant received robotic surgery (test group) and conventional surgery (control group) on contralateral quadrants. Primary outcomes were bone resection volume ratio (measured via pre-/post-op CBCT segmentation) and operative time. Secondary outcomes included nerve injury incidence and healing outcomes. Differences were analyzed via paired t-tests and generalized estimating equations. In this RCT of 10 children with impacted teeth, robotic surgery reduced total operative time by 35
Introduction: Autogenous tooth transplantation involves transferring a tooth within the same patient, requiring precise socket preparation that is technically challenging. This case demonstrates a robot-assisted technique to improve precision. Case description: A 46-year-old male with an unrestorable mandibular first molar (#46) underwent transplantation using the erupted third molar (#48) as the donor. Preoperative CBCT revealed #48′s bifurcated, longer roots necessitating osteotomy expansion. CBCT and intraoral scans were integrated into Dental Navi software for virtual planning, enabling automated osteotomy trajectory calculation. The robotic system performed osteotomy autonomously via foot pedal control, minimizing manual intervention. The donor tooth was transplanted and splinted, followed by root canal therapy at 2 weeks. Six-month follow-up showed successful outcomes. Discussion: This case report presents a preliminary application of an autonomous dental robotic system for performing patient-specific osteotomy with complex geometric configurations in the jawbone, potentially facilitating autogenous tooth transplantation. This initial attempt suggests that the technological approach may help reduce procedural complexity and could contribute to improved postoperative healing efficiency. Conclusion/clinical significance: Robotic assistance reduced surgical difficulty while preserving alveolar bone. The planned osteotomy enhanced primary stability, shortening healing time.
Introduction: Extensive maxillary defects challenge interim obturation due to labor-intensive traditional methods for required hollow prosthesis. This case presents a digital workflow enabling same-day delivery of closed hollow interim obturators. Case description: A 55-year-old patient scheduled for maxillectomy (squamous cell carcinoma) underwent preoperative intraoral scanning (Aoralscan 3, Shining 3D) to design a surgical obturator with cones for coronal cover positioning. The obturator was additive manufactured (Pro95 printer, SprintRay; Dentca Denture Base II/Teeth, Dentca) and seated intraoperatively. Post-surgery, it served as a custom tray for defect impressions. A coronal cover was digitally designed via ''Offset,'' ''Boolean subtraction,'' and ''Shell'' (Geomagic Wrap, 3D Systems), printed (Pro95), and bonded to the obturator using the denture base resin . Total chairside time was <2 hours. Discussion: The technique eliminated manual hollowing and casts, reducing prosthesis weight by 46.97% versus solid designs. Precise 2-mm coronal cover thickness ensured structural integrity and hermeticity, with no leakage at 3-month follow-up. Single-visit fabrication (1-hour printing/assembly) minimized clinical appointments, while high trueness reduced chairside adjustments. Conclusion/clinical significance: This digital approach streamlines rehabilitation, enhancing retention, comfort, and function for extensive maxillary defects. It demonstrates the viability of additive manufacturing in time-sensitive prosthetic care.
Aim or purpose: To delineate how Fasn-enriched circulating exosomes in diabetes disrupt endothelial lipid homeostasis and angiogenesis via mitochondrial regulation in the wound healing process. Materials and methods: Serum exosomes from type 2 diabetic mice and controls (n=10) were characterized by proteomics and lipidomics. Fasn-silenced exosomes were generated via AAV-edited donor mice (n=6) for diabetic wound models. Human umbilical vein endothelial cells (HUVECs) were treated with circulating exosomes, followed by lipidomics, RNA-seq, Seahorse mitochondrial assays and angiogenic detection. Molecular mechanisms (DRP1-Ser616 phosphorylation, mTOR-mitophagy axis, cGAS-STING, SASP factors) were analyzed through RNA-seq, immunoblotting, and pharmacological interventions. Results: Diabetic exosomes exhibited 3.2-fold higher Fasn than controls. Fasn transfer triggered lipid overload and oxidative stress in HUVECs, driving mitochondrial fission via Drp1-Ser616 phosphorylation. Lipid accumulation activated mTOR-dependent mitophagy inhibition, further resulting in excessive damaged mitochondria and mtDNA leakage. Cytosolic mtDNA activated cGAS-STING and upregulated SASP factors, impairing tube formation by 38%. Fasn silencing in diabetic mice restored angiogenesis (2.16-fold CD31+ vessels) and accelerated wound closure by 10.5% at D10 (P<0.01). Conclusions: Fasn-enriched circulating exosomes in diabetes drive diabetic angiogenesis impairment through lipid metabolism disturbance-induced mitochondrial fragmentation and SASP phenotype in endothelial cells. Targeting exosomal Fasn or quality control represents a translatable strategy for diabetic wound healing.
Aim or purpose: The deficiency of robust cytotoxic T lymphocyte (CTL) response and sustained anti-tumor microenvironment represents persistent dilemmas during tumor immunotherapy. Hence, rebooting the immune system to overcome existing intractable obstacles is pivotal. We developed a strategy of strengthening host and weakening tumor by constructing Nanodecoys to synergistically achieve tumor microenvironment immunosuppression reversal and induce antigen-specific immune response. Materials and methods: Nanodecoys were fabricated by integration of immunocompetent membrane with LPS/Decitabine-loading nanoparticles. The physicochemical and biological properties of Nanodecoys were characterized and detected in vitro. Primary, recurrent, and metastasis models of melanoma were constructed to investigate the inhibitory effect of Nanodecoys on tumor growth. RNA-seq analysis was applied to evaluate the effect on immune revitalization and tumor microenvironment. Results: Nanodecoys exhibited the excellent colloidal stability and biocompatibility. Nanodecoys blocked PD-L1/CD47 checkpoints and induced tumor-intrinsic pyroptotic cascades by LPS/Decitabine-mediated GSDMD cleavage in vitro. The released tumor lysates triggered the specific immune activation. In the tumor-bearing mice, infused Nanodecoys were enriched in lymph nodes and tumor foci, costimulated the innate immunity and induced tumor pyroptosis. Nanodecoys elicited a tumor suppressive efficacy greater than 90% in tumor growth, recurrence, and metastasis. The pyroptosis process primed potent CTL activation and specific memory T cells formation, establishing a long-term immune defense. Conclusions: Nanodecoys reprogram and enhance the efficacy of tumor immunotherapy through a two-pronged approach of immunosuppression reversal and pyroptosis induction, highlighting the potential of Nanodecoys as a self-amplifying anti-tumor immune circuit.
Aim or purpose: Segmental tracheal defects from maxillofacial trauma or tumor resection pose life-threatening airway compromise, yet current grafts fail to replicate biomechanical and vascular complexity. This study pioneers a clinically scalable approach integrating 3D-printed biomimetic minichannels, minced cartilage granules (CGs), and adipose mesenchymal stem cells (ADSCs) to engineer vascularized tracheal substitutes for reconstruction. Materials and methods: C-shaped polycaprolactone-polyglycerol sebacate scaffolds (4-layer coating) were fabricated via caramel-sacrificing 3D printing. Auricular/rib CGs (300–500 μm) from adult rabbits/minipigs were cryo-ground, mixed with ADSCs (3:1 ratio), and infused with platelet-rich plasma. Constructs were prevascularized subcutaneously (2 weeks) and orthotopically transplanted into 2 cm (rabbits, n=18) and 3 cm (minipigs, n=6) tracheal defects. Mechanical testing, proteomics, histology, and survival analysis were performed (ethics approval: No. 2023kq040). Results: ADSCs enhanced chondrocyte survival by upregulating glycolysis (hexokinase activity: 65.02 ± 3.61 U/gprot vs. 46.22 ± 2.35 in hypoxia, p*<0.01), enabling rapid vascularization (CD31+ vessels: 24.67 ± 4.73 vs. 3.33 ± 1.15 in controls, p*<0.01). Grafts achieved native-level compressive strength (2.15 ± 0.11 N vs. 1.69 ± 0.15 N for native ) and maintained luminal patency for 67 days in rabbits, while porcine models showed 80% 8-week survival. Conclusions: This study establishes a critical breakthrough in oral and maxillofacial surgery, offering an emergency-compatible solution for both wartime and peacetime airway salvage. The dual role of ADSCs in metabolic reprogramming and angiogenesis sets a paradigm for reconstructing craniofacial defects.
BACKGROUND:The microporous structure of porous titanium alloy may affect osteoblast differentiation and reduce effective elastic modulus (EEM) of the prostheses. Therefore, the biomechanics-based anatomic design of porous radial head prosthesis (PRHP) may help promote bone healing and reduce postoperative complications. METHODS:A microscopic-macro virtual testing platform (VTP) was built to design cells with excellent mechanical properties, further, to construct the PRHP. An intelligent anatomic platform of healthy human elbow-forearms was developed to construct finite element (FE) models of solid radial head prosthesis (SRHP) and PRHP replacement for Mason type III fractures. Axial and valgus loads were applied for surgical model validation and microscopic-macro biomechanical analysis. RESULTS:The order of ultimate compressive load (UCL) and yield strength (YS) of five types of cells is NEWTET>KAGOME>NEWPYRAMID>TET>PYRAMID. Under the same porosity conditions, UCL and YS of the double and four-layer lattice structures of NEWTET decreased by 62.39 %, 69.46 % and 61.70 %, 70.21 % compared to the single-layer, respectively. The EEM of NEWTET-based PRHP is 17.66 % of that of SRHP. Compared with the SRHP replacement, PRHP replacement reduced the humeral cartilage stress by 18.96 %-19.51 %. CONCLUSIONS:NEWTET cell has better microscopic mechanical properties and bone-growth adaptability. The EEM of NEWTET-based PRHP closely resembles cortical bone. Compared with SRHP replacement, microscopic-macro biomechanical performance in long-term after PRHP replacement is closer to that of a normal elbow joint. The microscopic-macro VTP and human intelligent anatomic elbow-forearm FE analysis systems provide efficient, accurate, and smart tools for the design of porous prostheses in joint replacement surgery.
Aim or purpose: This study evaluated the accuracy of robot-assisted osteotomy in endodontic microsurgery using different registration workflows. Materials and methods: Twelve printed mandibular jaw models were divided into 4 group. U-shape tube (UT) groups is divided as UT-O and UT-B groups (O/B: registration points at occlusal or buccal site). Cone-beam computed tomography (CBCT) images of jaw models with UT were scanned. Customised template (CT) groups, divided as CT-O and CT-B groups. Each jaw information from CBCT scan and intraoral scan without any additional device were obtained. The osteotomy was performed with a robotic system. The postoperative CBCT images were obtained. Platform, apex, angular deviations and registration time were compared. Multilevel linear regression models were used to evaluate the accuracy outcomes of the registration devices (UT or CT), registration location (buccal site or occlusal site), tooth type (premolars or molars), and dentition site (right or left). The registration times were compared using the nonparametric test (P<0.05). Results: A total of 72 sites were drilled in 12 models. Significant differences (P<0.01) among different registration location were found for all accuracy variables. No significant differences were found on other factors for all the accuracy variables. Less time was required for UT-B and CT-B groups. Conclusions: Robot-assisted osteotomy accuracy using UT registration workflow was similar to that of CT registration workflow. The buccal registration points were more accurate and efficient in robot-assisted osteotomy than occlusal registration points.
M2 macrophage–derived extracellular vesicles (M2-EVs) demonstrate the capacity to reduce pro-inflammatory M1 macrophage formation, thereby restoring the M1–M2 macrophage balance and promoting immunoregulation. However, the efficacy of M2-EVs in regulating macrophage polarization and subsequently enhancing osseointegration around titanium (Ti) implants in patients with diabetes mellitus (DM) remains to be elucidated. In this study, Ti implants were coated with polydopamine to facilitate M2-EVs adherence. In vitro experiment results demonstrated that M2-EVs could carry miR-23a-3p, inhibiting NOD-like receptor protein3(NLRP3) inflammasome activation in M1 macrophage and reducing the levels of inflammatory cytokines such as IL-1β by targeting NEK7. This improved the M1–M2 macrophage balance and enhanced mineralization on the Ti implant surfaces. The in vivo experiment results demonstrated that in diabetic conditions, the nanocoated M2-EVs significantly promoted high-quality bone deposition around the Ti implants. The current results provide a novel perspective for simple and effective decoration of M2-EVs on Ti implants; clinically, the method may afford osteoimmunomodulatory effects enhancing implant osseointegration in patients with DM.
Diabetic wound healing is critically impaired by dysregulated macrophage polarization, compromised endothelial angiogenic function, and diminished fibroblast proliferation/migration under persistent hyperglycemia. Current therapies, predominantly focused on single-cell targeting, lack coordinated modulation across these key cellular components. We developed a novel triple-targeting core-shell nanoparticle (miR-RPC) leveraging the shared integrin αvβ3 receptor on macrophages, endothelial cells, and fibroblasts to address this limitation. miR-RPC features an RGD/phosphatidylserine (PS)-modified lipid shell encapsulating a chitosan/miR-146a-5p core. This miRNA was selected as a model RNA because of its widely recognized beneficial role in three key cell types in wound healing. The RGD peptide enables specific αvβ3-mediated triple-targeting. The anionic lipid PS facilitates core-shell assembly via electrostatic interaction with the cationic chitosan/RNA core and mimics apoptotic signals to enhance macrophage phagocytosis and phenotypic transition. miR-RPC effectively reprogrammed macrophages towards the M2 phenotype, restored endothelial angiogenic capacity under high glucose, and stimulated fibroblast proliferation, migration, and collagen secretion. Incorporated into a gelatin methacrylate (GelMA)/oxidized hyaluronic acid (OHA) double cross-linked hydrogel (GelO), miR-RPC@GelO significantly accelerated diabetic wound healing in rat models, demonstrating reduced inflammation, increased vascular density, and enhanced collagen deposition. This innovative triple-targeting system achieves coordinated diabetic wound repair through synergistic “immunomodulation-angiogenesis-collagen deposition” mechanisms, offering a promising therapeutic approach. Furthermore, the successful preparation of miR-RPC expands the application of anionic lipids in RNA delivery systems and highlights its potential as a versatile gene delivery vector.