Rapid biodegradation of microplastics generated from bio-based thermoplastic polyurethane.

The accumulation of microplastics in various ecosystems has now been well documented and recent evidence suggests detrimental effects on various biological processes due to this pollution. Accumulation of microplastics in the natural environment is ultimately due to the chemical nature of widely used petroleum-based plastic polymers, which typically are inaccessible to biological processing. One way to mitigate this crisis is adoption of plastics that biodegrade if released into natural environments. In this work, we generated microplastic particles from a bio-based, biodegradable thermoplastic polyurethane (TPU-FC1) and demonstrated their rapid biodegradation via direct visualization and respirometry. Furthermore, we isolated multiple bacterial strains capable of using TPU-FC1 as a sole carbon source and characterized their depolymerization products. To visualize biodegradation of TPU materials as real-world products, we generated TPU-coated cotton fabric and an injection molded phone case and documented biodegradation by direct visualization and scanning electron microscopy (SEM), both of which indicated clear structural degradation of these materials and significant biofilm formation.

Molecular control of temporal integration matches decision-making to motivational state.

Motivations bias our responses to stimuli, producing behavioral outcomes that match our needs and goals. We describe a mechanism behind this phenomenon: adjusting the time over which stimulus-derived information is permitted to accumulate toward a decision. As a Drosophila copulation progresses, the male becomes less likely to continue mating through challenges. We show that a set of Copulation Decision Neurons (CDNs) flexibly integrates information about competing drives to mediate this decision. Early in mating, dopamine signaling restricts CDN integration time by potentiating CaMKII activation in response to stimulatory inputs, imposing a high threshold for changing behaviors. Later into mating, the timescale over which the CDNs integrate termination-promoting information expands, increasing the likelihood of switching behaviors. We suggest scalable windows of temporal integration at dedicated circuit nodes as a key but underappreciated variable in state-based decision-making.

Contextualizing sociocultural beliefs about cleft, knowledge of the treatments, and factors associated with delay of treatment in Eastern Indonesia.

INTRODUCTION: Indonesia is a multicultural Asian country with a high incidence of cleft. This study contextualizes how patients' sociocultural backgrounds hinder cleft management in a diverse nation. MATERIAL AND METHODS: This study involved 202 families of cleft patients attending six tertiary care hospitals in South Sulawesi between 2021 and 2022. A mixed-methods, descriptive cross-sectional study employed semi-structured interviews and focus group discussions. Thematic content analysis was done using Murdock's causal attribution of illness. Knowledge of the treatments and surgery expectations used open coding. We held medical team focus group discussions to validate education on treatments. Cleft management education was thematically analyzed based on Indonesia's Minister of Health Decree. RESULTS: Two hundred-two families and ten medical teams participated. Thematic content analysis revealed common beliefs and factors that hinder medical treatments. The participants were 109 Buginese, 57 Makassarese, 16 Durinese, 8 Luwunese, 8 Torajanese, and 4 Mandarese. 22.3 % were unaware of causation, while 29.2 % attributed it to natural causes. About half of the interviewees believed in supernatural attribution. Even though 40 % of participants knew little about the surgery, they agreed that surgery improves appearance and speech. Medical treatments are delayed due to a lack of treatment knowledge, parents' concerns about surgical safety, and beliefs about causes. DISCUSSION: Indigenous societies in South Sulawesi believe in supernatural causes of cleft. Most had incomplete surgical treatment information. An intensive educational health program about causes, treatments, medical specialists, and treatment goals is warranted to enhance patient compliance with medical treatment, ultimately leading to improved health outcomes.

Microfragmented Fat and Biphasic Calcium Phosphates for Alveolar Cleft Repair: Protocol for a Prospective, Nonblinded, First-in-Human Clinical Study.

BACKGROUND: Biphasic calcium phosphates (BCP) may serve as off-the-shelf alternatives for iliac crest-derived autologous bone in alveolar cleft reconstructions. To add osteoinductivity to the osteoconductive BCPs to achieve similar regenerative capacity as autologous bone, a locally harvested buccal fat pad will be mechanically fractionated to generate microfragmented fat (MFAT), which has been shown to have high regenerative capacity due to high pericyte and mesenchymal stem cell content and a preserved perivascular niche. OBJECTIVE: Our primary objectives will be to assess the feasibility and safety of the BCP-MFAT combination. The secondary objective will be efficacy, which will be evaluated using radiographic imaging and histological and histomorphometric evaluation of biopsies taken 6 months postoperatively, concomitant with dental implant placement. METHODS: Eight patients with alveolar cleft (≥15 years) will be included in this prospective, nonblinded, first-in-human clinical study. MFAT will be prepared intraoperatively from the patient's own buccal fat pad. Regular blood tests and physical examinations will be conducted, and any adverse events (AEs) or serious EAs (SAEs) will be meticulously recorded. Radiographic imaging will be performed prior to surgery and at regular intervals after reconstruction of the alveolar cleft with the BCP-MFAT combination. Biopsies obtained after 6 months with a trephine drill used to prepare the implantation site will be assessed with histological and histomorphometric analyses after methylmethacrylate embedding and sectioning. RESULTS: The primary outcome parameter will be safety after 6 months' follow-up, as monitored closely using possible occurrences of SAEs based on radiographic imaging, blood tests, and physical examinations. For efficacy, radiographic imaging will be used for clinical grading of the bone construct using the Bergland scale. In addition, bone parameters such as bone volume, osteoid volume, graft volume, and number of osteoclasts will be histomorphometrically quantified. Recruitment started in November 2019, and the trial is currently in the follow-up stage. This protocol's current version is 1.0, dated September 15, 2019. CONCLUSIONS: In this first-in-human study, not only safety but also the histologically and radiographically assessed regenerative potential of the BCP-MFAT combination will be evaluated in an alveolar cleft model. When an SAE occurs, it will be concluded that the BCP-MFAT combination is not yet safe in the current setting. Regarding AEs, if they do not occur at a higher frequency than that in patients treated with standard care (autologous bone) or can be resolved by noninvasive conventional methods (eg, with analgesics or antibiotics), the BCP-MFAT combination will be considered safe. In all other cases, the BCP-MFAT combination will not yet be considered safe. TRIAL REGISTRATION: Indonesia Clinical Trial Registry INA-EW74C1N; https://tinyurl.com/28tnrr64. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42371.

Anesthesia Techniques for Harvesting via Follicular Unit Excision.

Follicular unit excision (FUE) is one of the established techniques for harvesting donor hair for hair transplantation. Traditionally, hair restoration surgery is performed using local anesthesia, although some surgeons use general anesthesia for the procedure. Normally, local anesthesia is coupled with light oral sedation to make the procedure more comfortable for patients. Techniques such as "ring block" or nerve blocks are common and effective for scalp anesthesia. Due to its simplicity, adequate pain control and safety, ring blocks are typically used for FUE donor harvesting, reserving nerve blocks only to patients who cannot be adequately anesthetized with the ring block. Using the correct technique for application of local anesthesia can dramatically decrease the pain associated with it and create a comfortable and easy experience for the patient.

Advanced lung cancer patient benefits from minimally invasive costal resection and reconstruction: an effective palliative approach for costal metastasis.

We hereby describe the resection and reconstruction of a rib infiltrated by a lung cancer metastasis. Despite prior radiation therapy aimed at mitigating pain from rib infiltration in a stage IV non-small cell lung cancer patient, results were unsatisfactory. Employing a minimally invasive palliative strategy, we executed a successful operation to address this issue. This technique presents a viable alternative for patients experiencing recurrent pain post radiation therapy.

Final Results of GERDA on the Two-Neutrino Double-ß Decay Half-Life of

We present the measurement of the two-neutrino double-ß decay rate of ^{76}Ge performed with the GERDA Phase II experiment. With a subset of the entire GERDA exposure, 11.8 kg yr, the half-life of the process has been determined: T_{1/2}^{2ν}=(2.022±0.018_{stat}±0.038_{syst})×10^{21} yr. This is the most precise determination of the ^{76}Ge two-neutrino double-ß decay half-life and one of the most precise measurements of a double-ß decay process. The relevant nuclear matrix element can be extracted: M_{eff}^{2ν}=(0.101±0.001).

Cultural Beliefs on Cleft lip and/or Cleft Palate and Their Implications on Management: A Systematic Review.

OBJECTIVE: This article examines and summarizes the published epidemiological literature on cross-cultural variations. Particular emphasis was put on addressing cross-cultural beliefs on the causes, management, and attitude toward cleft lip and/or cleft palate. A healthcare provider's awareness of these cross-cultural attitudes and beliefs is vital for promoting effective collaboration with patients' families and ensuring a favorable medical outcome. DESIGN: Systematic review. SETTING: Not applicable. PARTICIPANTS: Patients with cleft lip and/or cleft palate, their families, their communities, and healthcare providers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: All relevant and eligible studies were identified using PubMed and Google Scholar databases. The cultural belief was categorized and measured using Murdock's Theories of Illness. The study was reported in compliance with PRISMA guidelines. The quality of the selected studies was evaluated in accordance with the Critical Appraisal Skills Programme criteria (CASP). Fourteen articles covering thirteen countries on four continents met the inclusion criteria. In diverse communities, cleft lip and/or cleft palate was attributed to natural (infection, medication, improper diet, smoke, or radiation) or supernatural (God, eclipse, ancestral spirit, and curse) causes. Reported consequences include stigmatization, inappropriate treatments, leaving patients untreated, and infanticide. CONCLUSION: Cultural beliefs are the main cause of misconceptions surrounding a cleft lip and/or cleft palate. There is also a need for public health care providers' intervention to educate society about the natural causes and ease of management, thereby increasing opportunities for patients substantially.

Search for tri-nucleon decays of 76Ge in GERDA.

We search for tri-nucleon decays of 76Ge in the dataset from the GERmanium Detector Array (GERDA) experiment. Decays that populate excited levels of the daughter nucleus above the threshold for particle emission lead to disintegration and are not considered. The ppp-, ppn-, and pnn-decays lead to 73Cu, 73Zn, and 73Ga nuclei, respectively. These nuclei are unstable and eventually proceed by the beta decay of 73Ga to 73Ge (stable). We search for the 73Ga decay exploiting the fact that it dominantly populates the 66.7 keV 73mGa state with half-life of 0.5 s. The nnn-decays of 76Ge that proceed via 73mGe are also included in our analysis. We find no signal candidate and place a limit on the sum of the decay widths of the inclusive tri-nucleon decays that corresponds to a lower lifetime limit of 1.2×1026 yr  (90% credible interval). This result improves previous limits for tri-nucleon decays by one to three orders of magnitude.

Long-Term Safety of Bone Regeneration Using Autologous Stromal Vascular Fraction and Calcium Phosphate Ceramics: A 10-Year Prospective Cohort Study.

This prospective cohort study aimed to assess long-term safety, dental implant survival, and clinical and radiological outcomes after maxillary sinus floor elevation (MSFE; lateral window technique) using freshly isolated autologous stromal vascular fraction (SVF) combined with calcium phosphate ceramics. All 10 patients previously participating in a phase I trial were included in a 10-year follow-up. They received either ß-tricalcium phosphate (ß-TCP; n = 5) or biphasic calcium phosphate (BCP; n = 5) with SVF-supplementation on one side (study). Bilaterally treated patients (6 of 10; 3 ß-TCP, 3 BCP) received only calcium phosphate on the opposite side (control). Clinical and radiological assessments were performed on 44 dental implants at 1-month pre-MSFE, and 0.5- to 10-year post-MSFE. Implants were placed 6 months post-MSFE. No adverse events or pathology was reported during a 10-year follow-up. Forty-three dental implants (98%) remained functional. Control and study sides showed similar peri-implant soft-tissue quality, sulcus bleeding index, probing depth, plaque index, keratinized mucosa width, as well as marginal bone loss (0-6 mm), graft height loss (0-6 mm), and graft volume reduction. Peri-implantitis was observed around 6 implants (control: 4; study: 2) in 3 patients. This study is the first to demonstrate the 10-year safety of SVF-supplementation in MSFE for jawbone reconstruction. SVF-supplementation showed enhanced bone regeneration in the short term (previous study) and led to no abnormalities clinically and radiologically in the long term.

Rhythmic oscillations in the midbrain dopaminergic nuclei in mice.

Introduction: Dopamine release in the forebrain by midbrain ventral tegmental nucleus (VTA) and substantia nigra pars compacta (SNc) neurons is implicated in reward processing, goal-directed learning, and decision-making. Rhythmic oscillations of neural excitability underlie coordination of network processing, and have been reported in these dopaminergic nuclei at several frequency bands. This paper provides a comparative characterization of several frequencies of oscillations of local field potential and single unit activity, highlighting some behavioral correlates. Methods: We recorded from optogenetically identified dopaminergic sites in four mice training in operant olfactory and visual discrimination tasks. Results: Rayleigh and Pairwise Phase Consistency (PPC) analyses revealed some VTA/SNc neurons phase-locked to each frequency range, with fast spiking interneurons (FSIs) prevalent at 1-2.5 Hz (slow) and 4 Hz bands, and dopaminergic neurons predominant in the theta band. More FSIs than dopaminergic neurons were phase-locked in the slow and 4 Hz bands during many task events. The highest incidence of phase-locking in neurons was in the slow and 4 Hz bands, and occurred during the delay between the operant choice and trial outcome (reward or punishment) signals. Discussion: These data provide a basis for further examination of rhythmic coordination of activity of dopaminergic nuclei with other brain structures, and its impact for adaptive behavior.

Development and systematic evaluation of decellularization protocols in different application models for diaphragmatic tissue engineering.

BACKGROUND: Tissue engineered bioscaffolds based on decellularized composites have gained increasing interest for treatment of various diaphragmatic impairments, including muscular atrophies and diaphragmatic hernias. Detergent-enzymatic treatment (DET) constitutes a standard strategy for diaphragmatic decellularization. However, there is scarce data on comparing DET protocols with different substances in distinct application models in their ability to maximize cellular removal while minimizing extracellular matrix (ECM) damage. METHODS: We decellularized diaphragms of male Sprague Dawley rats with 1 % or 0.1 % sodium dodecyl sulfate (SDS) and 4 % sodium deoxycholate (SDC) by orbital shaking (OS) or retrograde perfusion (RP) through the vena cava. We evaluated decellularized diaphragmatic samples by (1) quantitative analysis including DNA quantification and biomechanical testing, (2) qualitative and semiquantitative analysis by proteomics, as well as (3) qualitative assessment with macroscopic and microscopic evaluation by histological staining, immunohistochemistry and scanning electron microscopy. RESULTS: All protocols produced decellularized matrices with micro- and ultramorphologically intact architecture and adequate biomechanical performance with gradual differences. The proteomic profile of decellularized matrices contained a broad range of primal core and ECM-associated proteins similar to native muscle. While no outstanding preference for one singular protocol was determinable, SDS-treated samples showed slightly beneficial properties in comparison to SDC-processed counterparts. Both application modalities proved suitable for DET. CONCLUSION: DET with SDS or SDC via orbital shaking or retrograde perfusion constitute suitable methods to produce adequately decellularized matrices with characteristically preserved proteomic composition. Exposing compositional and functional specifics of variously treated grafts may enable establishing an ideal processing strategy to sustain valuable tissue characteristics and optimize consecutive recellularization. This aims to design an optimal bioscaffold for future transplantation in quantitative and qualitative diaphragmatic defects.

A narrative review of the role of Eph receptors in head and neck squamous cell carcinoma.

Tyrosine kinase receptors (TKR) coordinate a variety of pathological processes in head and neck squamous cell carcinoma (HNSCC), and eventually play a role in patient outcomes. In this review, the role of Eph receptors in HNSCC progression and the possibility of targeting these receptors are illustrated. All relevant studies were identified through a comprehensive search of four electronic databases, including PubMed, Scopus, web of science, and Embase till August 2022. EphA2 and EphB4, along with ephrin-B2, were the most extensively studied proteins in this family. However, overexpression of EphB4 and its ligand ephrin-B2 were the only proteins that consistently showed association with a poor outcome, indicating that these proteins might serve as valuable prognostic markers in HNSCC. High expression of EphA3 and EphB4 was found to play a crucial role in radioresistance of HNSCC. EphB4 loss, in particular, was observed to induce an immunosuppression phenotypic HNSCC. Currently, ongoing clinical trials are investigating the benefits of EphB4-ephrin-B2 blockade in combination with standard of care treatment in HNSCC. Further efforts are needed to explore the biological role and behavioral complexity of this family of TKR in HNSCC with great attention to avoid heterogeneity of HNSCC subsites.

Intraoperative Visualization and Treatment of Salivary Gland Dysfunction in Sjögren's Syndrome Patients Using Contrast-Enhanced Ultrasound Sialendoscopy (CEUSS).

In sialendoscopy, ducts are dilated and the salivary glands are irrigated with saline. Contrast-enhanced ultrasound sialendoscopy (CEUSS), using microbubbles, may facilitate the monitoring of irrigation solution penetration in the ductal system and parenchyma. It is imperative to test CEUSS for its safety and feasibility in Sjögren's syndrome (SS) patients. CEUSS was performed on 10 SS patients. The primary outcomes were safety, determined by the occurrence of (serious) adverse events ((S)AEs), and feasibility. The secondary outcomes were unstimulated and stimulated whole saliva (UWS and SWS) flow rates, xerostomia inventory (XI), clinical oral dryness score, pain, EULAR Sjögren's syndrome patient reported index (ESSPRI), and gland topographical alterations. CEUSS was technically feasible in all patients. Neither SAEs nor systemic reactions related to the procedure were observed. The main AEs were postoperative pain (two patients) and swelling (two patients). Eight weeks after CEUSS, the median UWS and SWS flow had increased significantly from 0.10 to 0.22 mL/min (p = 0.028) and 0.41 to 0.61 mL/min (p = 0.047), respectively. Sixteen weeks after CEUSS, the mean XI was reduced from 45.2 to 34.2 (p = 0.02). We conclude that CEUSS is a safe and feasible treatment for SS patients. It has the potential to increase salivary secretion and reduce xerostomia, but this needs further investigation.

Long-term near-continuous recording with Neuropixels probes in healthy and epileptic rats.

Neuropixels probes have become a crucial tool for high-density electrophysiological recordings. Although most research involving these probes is in acute preparations, some scientific inquiries require long-term recordings in freely moving animals. Recent reports have presented prosthesis designs for chronic recordings, but some of them do not allow for probe recovery, which is desirable given their cost. Others appear to be fragile, as these articles describe numerous broken implants.Objective.This fragility presents a challenge for recordings in rats, particularly in epilepsy models where strong mechanical stress impinges upon the prosthesis. To overcome these limitations, we sought to develop a new prosthesis for long-term electrophysiological recordings in healthy and epileptic rats.Approach.We present a new prosthesis specifically designed to protect the probes from strong shocks and enable the safe retrieval of probes after experiments.Main results.This prosthesis was successfully used to record from healthy and epileptic rats for up to three weeks almost continuously. Overall, 10 out of 11 probes could be successfully retrieved with a retrieval and reuse success rate of 91%.Significance.Our design and protocol significantly improved previously described probe recycling performances and prove usage on epileptic rats.

Liquid argon light collection and veto modeling in GERDA Phase II.

The ability to detect liquid argon scintillation light from within a densely packed high-purity germanium detector array allowed the Gerda experiment to reach an exceptionally low background rate in the search for neutrinoless double beta decay of 76 Ge. Proper modeling of the light propagation throughout the experimental setup, from any origin in the liquid argon volume to its eventual detection by the novel light read-out system, provides insight into the rejection capability and is a necessary ingredient to obtain robust background predictions. In this paper, we present a model of the Gerda liquid argon veto, as obtained by Monte Carlo simulations and constrained by calibration data, and highlight its application for background decomposition.

A network meta-analysis assessing the effectiveness of various radical and conservative surgical approaches regarding recurrence in treating solid/multicystic ameloblastomas.

Multiple treatment approaches have been undertaken to reduce the incidence of recurrence in solid/multicystic ameloblastoma (SMA), both conservative and radical. A network meta-analysis (NMA) was conducted to assess and compare the effectiveness of these various treatment approaches concurrently. This study was reported based on the Preferred Reporting Items for Systematic Reviews for Network Meta-Analysis (PRISMA-NMA) statement. PubMed (MEDLINE), ScienceDirect, Scopus, and Web of Science were searched until August 10, 2021. The NMA was conducted using the STATA program. Of 1153 records identified in the search, seven observational studies with 180 patients were included. Six different treatment approaches were identified. Segmental resection ranked highest for reducing the recurrence rate with the highest SUCRA score (77.7), followed by curettage with cryotherapy (66.9) and marginal resection (49.3). Network inconsistencies and publication bias appeared to be absent. According to the Confidence in Network Meta-Analysis (CINeMa) method, the evidence's certainty was low for all comparisons due to imprecision and within-study bias. In conclusion, this study is the first NMA in the field of ameloblastoma. Segmental resection seemed to be the most effective treatment approach for minimizing recurrence in SMA patients. Nevertheless, weak certainty of evidence makes that the results must be regarded with caution.

Stem Cell-Based Tissue Engineering for Cleft Defects: Systematic Review and Meta-Analysis.

This study aimed to analyze the efficacy of stem cell-based tissue engineering for the treatment of alveolar cleft (AC) and cleft palate (CP) defects in animal models.Systematic review and meta-analysis.Preclinical studies on alveolar cleft repair in maxillofacial practice.Electronic search was performed using PubMed, Embase, and Cochrane databases. Pre-clinical studies, where stem cell-based tissue engineering was used in the reconstruction of AC and CP in animal models were included. Quality of the selected articles was evaluated using SYRCLE (SYstematic Review Centre for Laboratory animal Experimentation).Review of alveolar cleft bone augmentation interventions in preclinical models.Outcome parameters registered were new bone formation (NBF) and/or bone mineral density (BMD).Thirteen large and twelve small animal studies on AC (21) and CP (4) reconstructions were included. Studies had an unclear-to-high risk of bias. Bone marrow mesenchymal stem cells were the most widely used cell source. Meta-analyses for AC indicated non-significant benefits in favor of: (1) scaffold + cells over scaffold-only (NBF P = .13); and (2) scaffold + cells over empty control (NBF P = .66; BMD P = .31). Interestingly, dog studies using regenerative grafts showed similar to superior bone formation compared to autografts. Meta analysis for the CP group was not possible.AC and CP reconstructions are enhanced by addition of osteogenic cells to biomaterials. Directions and estimates of treatment effect are useful to predict therapeutic efficacy and guide future clinical trials of bone tissue engineering.

Postoperative Daycare as a Safe and Cost-Effective Option for Secondary Alveolar Bone Graft (SABG) Surgery: A Retrospective Comparative Cohort Study.

OBJECTIVE: To evaluate the outcomes of Secondary Alveolar Bone Grafting (SABG) in patients treated either in daycare or with multiple day hospitalization (MDH) in relation to costs and complication rates. DESIGN: Retrospective comparative cohort study. SETTING: The data was collected from two settings: Postoperative daycare or MDH after oral cleft surgery in an Academic Medical Center in The Netherlands. PATIENTS: Data of 137 patients with unilateral Cleft lip, alveolus, and palate (CLAP) treated between 2006-2018 were evaluated. Registered clinical variables: age, gender, cleft subtype, bone donor site, type of hospitalization, length of stay, additional surgery, complications, surgeons, and costs. INTERVENTIONS: Closure of the alveolar cleft with/without closure of the anterior palate. MAIN OUTCOME MEASURES: Univariate analyses. RESULTS: Of the 137 patients, 46.7% were treated in MDH, and 53.3% in daycare. Total costs for daycare were significantly lower (P < .001). All patients treated in daycare received mandibular symphysis bone, whereas in MDH, 46.9% received iliac crest bone instead. Bone donor site was associated with postoperative care type. Complication rates were slightly but not significantly higher in daycare (26%) vs. MDH (14.1%) (P = .09). Most were Grade I (minor) according to Clavien Dindo classification. CONCLUSIONS: Daycare after alveolar cleft surgery is about as safe as MDH, but significantly cheaper.

Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration.

Targeting macrophages to regulate the immune microenvironment is a new strategy for bone regeneration with nano-drugs. Nano-drugs have achieved surprising anti-inflammatory and bone-regenerative effects, however, their underlying mechanisms in macrophages remain to be clarified. Macrophage polarization, immunomodulation, and osteogenesis are governed by autophagy. Rapamycin, an autophagy inducer, has shown promising results in bone regeneration, but high dose-mediated cytotoxicity and low bioavailability hinder its clinical application. This study aimed to develop rapamycin-loaded virus-like hollow silica nanoparticles (R@HSNs) which are easily phagocytosed by macrophages and translocated to lysosomes. R@HSNs induced macrophage autophagy, promoted M2 polarization, and alleviated the degree of M1 polarization as indicated by the downregulation of inflammatory factors IL-6, IL-1ß, TNF-α, and iNOS, and upregulation of anti-inflammatory factors CD163, CD206, IL-1ra, IL-10, and TGF-ß. These effects were nullified by cytochalasin B-induced inhibition of R@HSNs uptake in macrophages. The conditioned medium (CM) collected from R@HSNs-treated macrophages promoted osteogenic differentiation of mouse bone marrow mesenchymal stromal cells (mBMSCs). In a mouse calvaria defect model, free rapamycin treatment was inhibited, but R@HSNs robustly promoted bone defect healing. In conclusion, silica nanocarrier-mediated intracellular rapamycin delivery to macrophages effectively triggers autophagy-mediated M2 macrophage polarization, further enhancing bone regeneration by triggering osteogenic differentiation of mBMSCs.