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Surgical site infections are a major postoperative complication because microbial contamination may destabilize healing and undermine the effectiveness of regenerative biomaterials. Conventional approaches tend to focus on infection control and tissue regeneration in isolation, thereby restricting their efficacy in complicated surgical procedures. Recent advancements in bioinspired and living multiscale composite materials offer new methods of antimicrobial functionality and regenerative support through hierarchical material design and bioinspired strategies. This review presents an extensive discussion on bioinspired and living multiscale composites in regenerative medicine to address surgical site infections. This review discusses the principles of biology, design of multiscale architectures, and provides an overview of how inert implants have evolved into bioactive, antimicrobial, and adaptive multiscale material systems. Most important material classes and fabrication strategies are addressed, with literature on the modes of incorporating structural hierarchy, antimicrobial strategies, and biological integration through the composite platform. The existing uses in preventing infections, regeneration of contaminated defects, delivering infection-responsive drugs, and biosensing have been critically evaluated. Translational, industrial, and regulatory issues, as well as the problems of scale-up, manufacturing obstacles, biosafety, standardization, and clinical integration specifically for living and hybrid systems, are also discussed here. This review summarizes the prospects and shortcomings of multiscale composite strategies through the synthesis of materials science, biology, and translational research to identify key directions for creating effective, safe, and clinically viable anti-infective regenerative materials.

Prepectoral breast reconstruction (PBR) offers several advantages, including reduced postoperative pain, fewer animation deformities, shorter operative time, better aesthetic outcomes, and greater patient comfort, and has gradually become an important option for post-mastectomy reconstruction. However, most current prepectoral reconstruction procedures still rely on mesh (such as acellular dermal matrix [ADM] or synthetic mesh) to enhance soft tissue coverage and reduce the risk of implant-related complications, such as capsular contracture and implant exposure. The use of mesh, however, also introduces additional concerns, including high cost, risk of infection, and foreign body reactions. Therefore, this study aims to compare two surgical approaches-prepectoral breast reconstruction with mesh (PBR with mesh) and prepectoral breast reconstruction without mesh (PBR without mesh)-in breast cancer patients, evaluating their clinical outcomes and aesthetic results, and to summarize the advantages of mesh-free prepectoral breast reconstruction. This study retrospectively analyzed the clinical data of 246 patients who underwent PBR between June 2023 and December 2024. Patients were divided into two groups according to the surgical approach: the mesh-free group (128 cases, including 26 who received postoperative radiotherapy) and the mesh group (118 cases, including 25 who received postoperative radiotherapy). Baseline characteristics, perioperative indicators (such as operative time and blood loss), and postoperative complications (including infection, capsular contracture, and implant loss) were thoroughly evaluated and subjected to cost analysis. A subgroup analysis was performed specifically for the 51 patients who received postoperative radiotherapy (26 in the mesh-free group and 25 in the mesh group), with particular focus on comparing the incidence of capsular contracture between the two groups. In addition, the BREAST-Q questionnaire was used to systematically assess patients' postoperative quality of life and satisfaction. Regarding major complications, no statistically significant differences were observed between the mesh-free and mesh groups: infection rate (3.13% vs. 5.08%, p=0.527), severe capsular contracture rate (2.34% vs. 4.24%, p=0.486), wound dehiscence (2.34% vs. 3.39%, p=0.713), and implant loss rate (2.34% vs. 3.39%, p=0.713) (all p>0.05). Regarding perioperative indicators, there was no statistically significant difference in intraoperative blood loss and postoperative drainage volume between the two groups. The operation time in the non-patch group was significantly shorter than that in the patch group (107.50 [95.00, 120.00] vs. 125.00 [115.00, 135.00] minutes, p<0.001) and lower hospitalization costs (42,242.36 [39,999.14, 44,628.14] RMB vs. 60,083.01 [57,592.06, 63,443.36] RMB, p<0.001). In the subgroup analysis of 51 patients who received postoperative radiotherapy, the incidence of severe capsular contracture was higher in the mesh group compared with the mesh-free group (20% vs. 7.7%), although the difference did not reach statistical significance (p=0.193). BREAST-Q results showed no significant differences between the two groups in Satisfaction with breasts (54.00 [53.00, 56.00] vs. 53.50 [52.00, 55.00], p=0.051), Psychological well-being (39.50 [38.00, 41.00] vs. 39.00 [37.00, 40.00], p=0.092), or Sexual well-being (19.00 [18.00, 20.00] vs. 19.00 [18.00, 19.25], p=0.179). However, the mesh-free group had significantly higher scores in Physical well-being: chest (31 [29, 32] vs. 27 [25, 33.25], p=0.005). In selected patient populations, mesh-free prepectoral breast reconstruction is a safe and cost-effective option.

Urethral reconstruction often fails due to the foreign body reaction (FBR) triggered by the graft, leading to chronic inflammation, fibrosis, and lumen obstruction. To address this challenge, we developed an innovative strategy: a 3D-printed polylactic acid (PLA) scaffold was pre-implanted subcutaneously for 14 days to recruit host-derived fibroblasts, monocytes, and adipose-derived stem cells. These cells secreted a biomimetic extracellular matrix (ECM) rich in collagen, elastin, and glycosaminoglycans (GAGs), resulting in a proteoglycan (PG)-enriched, bioactive tissue-engineered urethral graft (TEUG). This PG-rich matrix interface, characterized by a high density of proteoglycans and glycosaminoglycans that mimic the native urethral microenvironment, closely mimicked native urethral tissue in terms of hydrophilicity, surface topography, roughness, and mechanical compliance. More importantly, compared with commercially available small intestinal submucosa (SIS)-based grafts, it significantly enhanced urothelial cell adhesion, spreading, and oriented spatial organization, effectively recapitulating the functional role of the native PG matrix. In a rabbit anterior urethral replacement model, TEUG not only provided essential structural support and elasticity but also maintained the tubular architecture and physiological distensibility of the urethra to accommodate pressure changes during voiding. Furthermore, it acted as a functional bioactive interface that modulated the local immune microenvironment, attenuated inflammatory responses, and resisted FBR. As a result, tissue homeostasis was preserved and regenerative capacity was promoted, leading to early and orderly re-epithelialization with successful formation of a continuous epithelial layer and contractile smooth muscle tissue. In contrast, SIS-mediated regeneration resulted in aberrant epithelial hyperplasia, ultimately causing luminal narrowing or complete occlusion. Throughout the postoperative observation period, TEUG-reconstructed urethras consistently maintained patent lumens and demonstrated superior voiding function. In summary, by engineering an ECM interface with immunomodulatory and anti-FBR properties, our approach offers a simple, efficient, and clinically translatable strategy to achieve functional regeneration in urethral reconstruction.

Conventional morphology-based planning (MB) in total knee arthroplasty (TKA) often results in imbalanced medial-lateral loading, which is a major risk factor for prosthesis loosening. This study aimed to evaluate a full-flexion gap balance planning (GB) approach and compare its biomechanical performance with MB planning. TKA surgical planning was performed on eight subjects. In vivo knee kinematics were obtained using a dual X-ray imaging system. The implant position was optimized within an in silico surgical-planning framework by minimizing medial-lateral gap differences across the full flexion range using in vivo dynamic kinematics. Using 3D-printed in vitro models, joint contact forces were measured at various flexion angles to compare medial-lateral load distribution between GB and MB planning. GB planning optimized femoral varus/valgus by approximately 4&#xb0; within anatomical constraints, significantly reducing the medial-lateral gap difference to a mean of&#x2009;<&#x2009;1&#xa0;mm across the entire flexion range (p&#x2009;<&#x2009;0.05). In contrast, the medial-lateral gap difference exceeded 2&#xa0;mm with MB planning. Furthermore, at mid-to-high flexion angles (30&#xb0;-100&#xb0;), GB planning reduced the medial-lateral load imbalance by approximately 38%-67% compared with MB planning (p&#x2009;<&#x2009;0.05). GB planning significantly improves medial-lateral load balance across the full range of flexion compared to conventional MB planning. This personalized planning optimizes joint loading patterns in vitro, which may theoretically align with principles aimed at reducing flexion-related adverse outcomes.

Partial edentulism in the posterior maxilla is frequently complicated by alveolar bone resorption and maxillary sinus pneumatization, limiting implant placement and negatively affecting oral health-related quality of life (OHRQoL). Minimally invasive sinus augmentation techniques, such as CAS KIT-assisted indirect sinus elevation, aim to reduce surgical morbidity; however, evidence regarding patient-reported outcomes and quality of life following such interventions remains limited. To evaluate oral health-related quality of life and patient-reported outcomes following implant rehabilitation using CAS KIT-assisted indirect maxillary sinus augmentation. This longitudinal observational study included 34 patients who underwent CAS KIT-assisted transcrestal sinus augmentation with implant placement in the posterior maxilla. Postoperative recovery and satisfaction were assessed using the HRQOLquestionnaire over seven postoperative days. OHRQoL was evaluated using the OHIP-14 questionnaire at baseline and one month after prosthetic rehabilitation. Data were analyzed using repeated measures ANOVA with a significance level set at p&#xa0;<&#xa0;0.05. HRQOLscores showed a statistically significant improvement over the seven-day postoperative period (p&#xa0;<&#xa0;0.001), with stabilization observed from Day 5 onward. OHIP-14 scores demonstrated a highly significant reduction from baseline to post-intervention assessment (p&#xa0;<&#xa0;0.001), indicating marked improvement in OHRQoL across all participants. CAS KIT-assisted indirect sinus augmentation followed by implant rehabilitation results in rapid postoperative recovery and significant improvement in patient-reported outcomes, supporting its role as a predictable and patient-centered treatment modality for posterior maxillary rehabilitation.

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Three-dimensional (3D) bioprinting enables the fabrication of complex tissue constructs with integrated vascular architectures, offering promising applications in transplantation. It is commonly assumed that dense, pre-formed microvascular networks are required to ensure survival and function of bioprinted organs immediately after implantation.&#xD;This in vivo study aimed to evaluate the feasibility of bioprinting and transplanting a vascularized pancreatic tissue construct featuring a single perfusable vessel in a porcine model, with a focus on maintaining stable perfusion and supporting post-transplantation microvascular development.&#xD;The study included 14 pigs, in which a 3D-bioprinted construct was transplanted and connected to the iliac artery or abdominal aorta. Two vascular connection strategies were evaluated: the Decell group (n = 5), using decellularized and recellularized external vessels for anastomosis, and the Bionic group (n = 9), using a vascular prosthesis. Immediate perfusion was achieved in all transplanted constructs. Three animals from the Bionic group completed a 4 week follow-up period. Computed tomography imaging and histopathological analyses demonstrated sustained perfusion of the constructs and progressive development of microvascular structures within the bioprinted tissue over time.&#xD;These findings demonstrate the feasibility of fabricating and transplanting a perfusable, mechanically stable, bioprinted pancreatic tissue construct capable of supporting in vivo vascular remodeling without a pre-fabricated dense capillary network. This work provides a preclinical proof-of-feasibility for simplified vascular design strategies in bioprinted tissue constructs and supports their further development toward translational applications.

Augmentation of the alveolar ridge became the backbone for treating the atrophic alveolar ridge. Several augmentation techniques have been proposed for this to compensate for changes in anatomy and ridge morphology and achieve aesthetic and biomechanical outcomes for the implant treatment plane. Increasing bone volume enhances implant stability and long-term implant survival. To compare the efficacy of bovine block inlay graft vs. Onlay graft for 3D alveolar ridge augmentation in the mandible. Twenty-four patients were randomly assigned to the Inlay and Onlay groups. The mandibular ridge was separated for the Inlay group, and a bovine bone block was placed in the space and secured with screws and a microtitanium plate. On a particulate bovine graft, the defect site was decorated and pre-adapted titanium was placed on a 3D module secured with titanium screws for the Onlay group. ONDEMOND software was used to estimate bone volume and evaluate bone density from cone beam computed tomography images, obtained both before and 6 months after surgery. A statistically significantly greater horizontal bone gain was observed in the Onlay group compared to the Inlay group (p = .033), while no statistically significant difference was found in vertical bone gain (p = .606). A comparable amount of vertical bone gain was observed between the two techniques, whereas the Onlay approach was associated with a statistically significantly greater horizontal bone gain. This randomized clinical trial was retrospectively registered at the Pan African Clinical Trial Registry (PACTR202412832590378).

Cell volume serves as a macroscopic indicator of cellular metabolism, growth, and signal transduction. Understanding how cell volume varies across macrophage phenotypes is essential for interpreting their functional states and activation processes. We present a label-free, noninvasive method for 3D morphological characterization and volume quantification of macrophages and apply it to monitor volume variations during their biological behaviors. We employed a home-made off-axis digital holographic microscopy (DHM) system based on a Mach-Zehnder interferometric configuration to reconstruct the 3D morphology of cells. Using the mathematical relationship between the phase map and the cell thickness, we further calculated their cellular volume. Our measurements show that M0 macrophages have a nearly spherical morphology with a volume of 970.54 &#xb1; 153.15 &#x2009;&#x2009; &#x3bc; m 3 . M 1 macrophages exhibit a flattened, pancake-like morphology with pseudopodia, with a significantly larger volume of 3822.00 &#xb1; 437.45 &#x2009;&#x2009; &#x3bc; m 3 . M 2 macrophages present a morphology resembling that of M 0 cells but with a volume of 2743.10 &#xb1; 254.67 &#x2009;&#x2009; &#x3bc; m 3 . It indicates that the cell volume might be a potential parameter to distinguish different polarized macrophages. In addition, we successfully monitored the volume changes of macrophages during cell death, cell division, and the polarization process from M 0 to M 1 . The cell-death process behaved as expected, with the cell volume continuously decreasing and eventually reaching a plateau. The division event we observed occurred together with cell death; during division, the total volume of the cell cluster increased sharply and then gradually decreased as cell death progressed. During the 8-h M 0 -to- M 1 polarization process, two phases of gradual volume increase and two phases of rapid volume increase were observed. In the early stage (0 to 2&#xa0;h), M 0 macrophages were likely not fully activated, showing only mild volume changes but still exhibiting an increasing trend. At 6 to 8&#xa0;h, the cells undergo a sharp increase in volume, reflecting their full activation and transition toward the M 1 phenotype. We demonstrate that DHM offers a powerful label-free strategy for quantifying macrophage volume and capturing the volume dynamic. It might be a potential approach for a macroscopic characterization to observe intracellular activities.

Three-dimensional X-ray histology offers a non-invasive alternative to conventional 2D histology, enabling volumetric imaging of biological tissues without physical sectioning or chemical staining. However, the intrinsic greyscale contrast of X-ray tomography limits its biochemical specificity compared with traditional histological stains. In this study, we extend deep-learning-based virtual staining to the X-ray domain via cross-modality image translation to generate artificially stained slices directly from synchrotron radiation microtomography (&#xb5;CT) scans. Using over 50 co-registered pairs of &#xb5;CT and toluidine blue-stained histology from bone-implant samples, we trained a modified CycleGAN network tailored for limited paired data. Whole-slide histology images were downsampled to the CT voxel size, with on-the-fly data augmentation for patch-based training. The model incorporates pixelwise supervision and greyscale consistency losses, enabling histologically realistic colour outputs while preserving structural detail. Results outperformed Pix2Pix and standard CycleGAN baselines across metrics of structural similarity, perceptual fidelity, and peak signal-to-noise ratio. Once trained, the model can be applied to full &#xb5;CT volumes to produce virtually stained 3D datasets that enhance interpretability without additional sample preparation. This work introduces virtual staining to 3D X-ray imaging, which may provide a scalable route for chemically informative, label-free tissue characterization in biomedical research.

Adenomyosis is increasingly diagnosed in reproductive-aged patients, particularly those undergoing assisted reproductive technology, due to advances in imaging and standardized diagnostic criteria. Its association with infertility and adverse obstetric outcomes has prompted growing interest in understanding disease mechanisms, prognostic features, and optimal fertility-focused management strategies. This review summarizes recent evidence on the pathophysiology, diagnosis, and treatment of adenomyosis in the context of reproductive outcomes. Emerging data highlight multifactorial mechanisms linking adenomyosis to impaired implantation and placentation, including hyperestrogenism, progesterone resistance, junctional zone disruption, immune dysregulation, and chronic inflammation. Studies evaluating imaging features suggest that disease phenotype, lesion size, uterine volume, and junctional zone involvement may influence reproductive outcomes, though findings remain inconsistent. Treatment strategies are evolving, with gonadotropin-releasing hormone agonists, levonorgestrel intrauterine systems, and aromatase inhibitors widely used, and growing evidence supporting pretreatment with prolonged gonadotropin-releasing hormone agonists. Adjunct approaches targeting inflammation, uterine contractility, and hormonal pathways are under investigation. Fertility-preserving procedures, including high-intensity focused ultrasound and adenomyomectomy, show promising but heterogeneous reproductive results. Adenomyosis remains a clinically heterogeneous condition requiring individualized fertility management. Standardized diagnostic frameworks and well designed prospective studies are needed to clarify prognostic factors and optimize therapeutic strategies to improve reproductive outcomes.

Access to cardiac implantable electronic device (CIED) therapy varies substantially across Europe, yet data from the ESC EuroAsia region remain limited. We aimed to compare implantation activity of pacemakers (PM), implantable cardioverter-defibrillators (ICD), and cardiac resynchronization therapy (CRT) devices across ESC EuroAsia Task Force (TF) countries, and to examine how infrastructure, workforce capacity, and health financing patterns relate to device uptake. National-level aggregated data were collected in 2025 through a standardized ESC EuroAsia TF survey and contextualized using EHRA Atlas indicators and World Bank/WHO health expenditure data. Implantation rates per million population were compared across Armenia, Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan, Turkmenistan, and Uzbekistan. Pacemaker implantation showed moderate variability (21-333 per million), whereas ICD (0.1-172 per million) and particularly CRT (1-135 per million) implantation demonstrated pronounced disparities. Countries with higher density of implanting centers and greater electrophysiology workforce availability-most notably Georgia-had substantially higher per-capita ICD and CRT implantation rates. Exploratory analyses suggested moderate positive correlations between national health expenditure (%GDP) and ICD and CRT implantation rates, whereas financing structure (out-of-pocket vs. government share) showed no consistent association. CIED implantation activity in the ESC EuroAsia region follows a clear complexity gradient (PM > ICD > CRT), indicating that access to advanced device therapy is primarily determined by system capacity rather than guideline awareness alone. Strengthening predictable reimbursement pathways, structured referral networks, workforce development, and national registries may reduce inequities and narrow the evidence-practice gap in sudden cardiac death prevention and heart failure management.

Pathological activity within frontal cortical circuits is common in many neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD). We developed an invasive brain mapping protocol in which temporary electrodes are implanted in candidate sites to identify personalized stimulation targets that can acutely relieve OCD symptoms. We found that stimulation within segments of the anterior limb of the internal capsule (ALIC) focally suppressed the structurally and functionally connected region of prefrontal and cingulate cortex. By leveraging the topographic organization of the ALIC, we reversibly inactivated frontal cortical sites with ALIC stimulation to determine which cortical regions are necessary for sustaining OCD symptoms. Stimulation of ventral capsule (VC) near the globus pallidus within the ALIC was associated with suppression of lateral orbitofrontal cortex activity and acute and long-term improvements in OCD symptoms. These results provide a paradigm for leveraging ALIC topography to deliver targeted connectomic neuromodulation to frontal cortex to treat neuropsychiatric disorders.

Transcatheter tricuspid valve replacement (TTVR) is an emerging therapy for severe tricuspid regurgitation with an evolving complication profile. Fatal prosthetic valve endocarditis (PVE) following orthotopic TTVR appears exceptionally rare, with detailed pathologic description through specialist cardiovascular autopsy remaining limited. A 65-year-old man with severe functional tricuspid regurgitation and persistent atrial fibrillation underwent TTVR. The following day, he developed complete heart block requiring pacemaker implantation. He remained well at 1 and 3 months, with improving symptoms and unremarkable bloods. At 6 months, he developed nonspecific viral-like symptoms over 48 hours culminating in death at home. Routine postmortem examination attributed death to coronary artery disease. Specialist cardiovascular pathology demonstrated PVE with large vegetations, atrioventricular nodal obliteration, left atrial communication enabling systemic septic embolization, diffuse coronary microembolization, and widespread left ventricular microabscesses. Fatal PVE after TTVR may present with nonspecific prodromal symptoms. Unexplained death after transcatheter valve intervention warrants specialist cardiovascular pathology. Prosthetic valve endocarditis after transcatheter tricuspid valve replacement may present with nonspecific symptoms and rapid clinical deterioration; unexplained death should prompt specialist cardiovascular pathology.

Evidence for a bilateral cochlear implant (BiCI) advantage in quiet is inconsistent, in part because many studies compare binaural versus acutely monaural conditions within BiCI users, which cannot model long-term unilateral (UniCI) adaptation. The authors asked whether BiCI confers a measurable benefit over UniCI for speech perception in quiet after rigorously controlling selection bias, and which patient factors modulate this benefit. Single-center retrospective cohort of 184 postlingually deafened adults (109 UniCI, 75 BiCI) implanted between February 2013 and March 2025. The authors performed 1:1 propensity-score matching (PSM) using age, sex (exact match), and principal component composites of preoperative audiology to yield 120 patients (60 UniCI, 60 BiCI) with excellent balance. Speech perception in quiet (mono-, di-syllable, sentence) was assessed at 3, 6, and 12 months after activation. Longitudinal trajectories were analyzed with linear mixed-effects models, with cumulative auditory experience (Average Daily Device Use &#xd7; Months Post-Activation) modeled via restricted cubic splines. Prespecified interactions tested effect modification by sex, age group (20 to 50 versus 50 to 70), cumulative use, and preoperative performance. Sensitivity analyses used a stricter PSM caliper (0.1). Before matching, BiCI recipients-despite poorer baselines-improved more steeply and achieved higher scores across time points. After PSM, BiCI showed a significant main effect for monosyllabic word recognition (&#x3b2; = 12.70, p = 0.005), with parallel results under stricter matching (&#x3b2; = 13.53, p = 0.005). Cumulative auditory experience strongly predicted improvement (both spline terms p < 0.001), but there was no significant Group &#xd7; Cumulative-use interaction, indicating comparable use-performance slopes in BiCI and UniCI. Thus, the BiCI advantage cannot be attributed to greater device use. A significant Preoperative Score &#xd7; Sex interaction (&#x3b2; = 14.49, p = 0.021) indicated that higher preoperative performance was more prognostic in males than females; this effect was specific to monosyllables. Disyllables showed a smaller yet significant BiCI effect; sentences trended in the same direction. Age group (20 to 50 versus 50 to 70) did not significantly modify the BiCI effect, and combining age groups was required to detect statistical significance, consistent with an age-independent bilateral benefit. In a rigorously matched cohort with longitudinal modeling, BiCI yielded a robust advantage over UniCI for quiet monosyllabic recognition that persisted after controlling for behavioral and demographic confounders. The absence of a Group &#xd7; Use interaction and the pattern restricted to low-context tasks support an interpretation most consistent with neurophysiological mechanisms (e.g., binaural summation, interaural-timing integration, cortical-level plasticity), rather than motivational or selection-related artifacts. Because this advantage was not significantly modified by age, the data suggest that bilateral stimulation offers broadly preserved benefits across adult age ranges. These findings provide clinically actionable evidence to inform counseling and strengthen policy discussions on expanding adult coverage from unilateral to bilateral implantation under public insurance frameworks. Larger, prospective cohorts with mechanistic endpoints remain essential to confirm durability, generalizability, and neural underpinnings.

Osteoporosis is a prevalent metabolic skeletal disorder characterized by reduced bone mass, deteriorated trabecular microarchitecture, and increased fragility fracture risk, imposing substantial global medical, social and economic burdens. Current first-line antiresorptive and anabolic therapeutics are severely constrained by long-term adverse reactions, insufficient patient adherence, and compromised bone microenvironment remodeling capacity, leaving a large unmet clinical demand for multitargeted and translational interventions. The gut-bone axis has been recognized as a core interorgan regulatory signaling network, in which gut microbiota orchestrates bone homeostasis through multiple cascaded mechanisms, including microbial metabolite production (short-chain fatty acids, tryptophan derivatives and bile acids), osteoimmune balance modulation (Th17/Treg axis and macrophage polarization), intestinal barrier maintenance, as well as the regulation of estrogen bioavailability, calcium-phosphorus absorption and vitamin D/VDR signaling. In parallel, advanced functional biomaterials, including modified bone cements, injectable hydrogels, intelligent nanocarriers and immune-regulatory scaffolds, have overcome the defects of conventional bone grafts and inert implant materials, exhibiting tunable mechanical properties, controllable degradation and precise bioactive cargo delivery for osteoporotic bone repair. Notably, the emerging integration of biomaterial engineering with gut-bone axis microbiology has established an innovative "material-microbiota-metabolism-bone" therapeutic paradigm. rationally designed gut-targeted biomaterial platforms, such as metabolite-releasing nanoparticles, probiotic-encapsulated microcarriers and ion-doped multifunctional hydrogels, enable simultaneous local bone defect reconstruction and systemic intestinal microecology homeostasis regulation, thereby alleviating gut dysbiosis-derived chronic inflammation and preventing progressive bone loss. This review systematically elaborates the core molecular and pathological mechanisms by which gut microbiota regulates osteoporosis progression, summarizes the research advances and inherent limitations of traditional bone repair biomaterials, and highlights the latest progress of multifunctional biomaterials targeting gut-bone axis crosstalk. We further conduct a critical comparison of three mainstream administration routes (oral delivery, local bone delivery and systemic delivery) in terms of targeting efficiency, biosafety and clinical applicability, and clarify the translational trade-offs of different material-based strategies. Despite encouraging preclinical outcomes, the clinical translation of gut microbiota-modulating biomaterials remains hindered by individual microbial heterogeneity, long-term biocompatibility risks, and incomplete clarification of material-gut-bone interactive mechanisms. Collectively, this comprehensive review constructs a refined interdisciplinary framework and provides actionable theoretical guidance for the development of next-generation personalized, multi-pathway combined biomaterial therapies for osteoporosis.