In this study, we aimed to overcome poor osseointegration at the implant-bone interface by engineering a bioactive interface using the polymer-induced liquid precursor strategy. By systematically modulating mineralization parameters, we constructed biomimetic mineralized collagen (BMC)-modified interfaces on 3D porous titanium alloy implants. The optimized composite interface exhibited homogeneous mineralized collagen distribution and significantly enhanced physicochemical properties, including a 32 degrees reduction in water contact angle, along with 1.6- and 1.4-fold increases in histone and albumin adsorption, respectively. These modifications promoted cell adhesion and osteogenic differentiation, as evidenced by 1.8-fold higher mineral deposition, 2.4-fold elevated ALP activity, and upregulated ALP, RUNX-2, BMP-2, and Col I expression. In a rabbit femoral condyle defect model, the BMC-modified interface upregulated osteogenesis-related genes (RUNX-2, ALP, and BMP-2) and increased the mineral apposition rate by 33%. It also enhanced new bone volume within the implant by 55%, improved bone formation in defect regions by 38%, and increased interfacial bonding strength by 2.8-fold. These findings provide a theoretical foundation and demonstrate the clinical potential of this strategy for next-generation biofunctionalized orthopedic implants. (c) 2026 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology.

The Salter osteotomy (SO) and the Pemberton osteotomy (PO) are common surgical methods for treating paediatric developmental dysplasia of the hip (DDH). Although they each have their own advantages, complications resulting from open surgeries are still relatively common. This study aimed to evaluate the clinical outcomes of SO and PO in the treatment of DDH and to identify prognostic factors associated with postoperative outcomes. Between April 2011 and May 2018, we retrospectively reviewed 72 DDH patients who underwent open reduction combined with pelvic osteotomy (SO/PO) at our hospital, and divided them into two groups based on the different surgical procedures: SO and PO. The minimum follow-up duration was 5 years. Subsequently, general patient information, along with clinical and radiographic results, were collected for comparative analysis. We introduced the congruity index, defined as the percentage of femoral head coverage by the acetabulum, to evaluate the prognosis of DDH. The Pearson’s chi-square test and Student t tests were used for comparisons of outcomes between the groups. Multivariable logistic regression models were used to analyze factors associated with avascular necrosis (AVN) and with the poorer McKay classification. A total of 65 patients completed the final follow-up. Laterality, duration of follow-up, and preoperative CEA differed significantly between the groups. Patients in the SO group had higher postoperative congruity index than those in the PO group (P < 0.001). According to the Severin and McKay classifications, satisfactory radiographic outcomes (Severin class I or II) were achieved in 88.9

The regeneration of aged bone is severely compromised by a deteriorating microenvironment characterized by excessive reactive oxygen species (ROS) and consequential endoplasmic reticulum stress (ERS). Herein, we report a biomimetic nanozyme engineered through synergistic p-d orbital hybridization and youthful membrane camouflage to precisely reverse this degenerative cascade. The designed Cu-Sn dual-atom core exhibits exceptional multi-enzymatic activity, scavenging superoxide anions with a 2.5-fold higher efficiency than Cu single-atom control. Mechanistic studies confirm that p-d hybridization redistributes electron density at the Sn site, lowering the energy barrier for ROS adsorption and conversion. This catalytic core is cloaked with a hybrid membrane derived from young mesenchymal stem and endothelial cells, which facilitates targeted delivery to senescent bone niches and provides intrinsic pro-regenerative signals. The composite nanozyme effectively mitigates intracellular oxidative stress and ERS in aged cells, rescuing their osteogenic and angiogenic potential. In an aged mouse model of jawbone defect, a single treatment regimen promoted robust bone regeneration, increasing the bone volume fraction (BV/TV) by 1.7-fold and significantly enhancing new bone mineralization. This work establishes a dual-principle design-orbital hybridization for catalytic amplification and youthful membrane for targeted rejuvenation-offering a versatile platform for treating a spectrum of senescence-associated diseases.

Diabetic wound healing is impaired by the loss of mechanical tension at wound edges, a key driver of cellular proliferation and migration. This process remains unaddressed by conventional biochemical-focused therapies. Therefore, a shape memory adhesive regenerative therapeutic (SMART) patch was engineered for autonomous mechanical contraction and sustained bioactive ion release. The SMART patch consists of a shape memory polymer layer (LA-CA@Fe SMP) and an adhesive layer (LA-Zn Adhesive). The LA-CA@Fe SMP exhibited high shape recovery rate triggered at body temperature. The LA-Zn Adhesive offered robust wet adhesion with an interfacial shear strength of 22.30 kPa and controlled Zn2+ delivery. The patch demonstrated antibacterial efficacy and promoted fibroblast proliferation. In diabetic mice, the SMART patch achieved wound traction and promoted collagen deposition that accelerated wound closure by 50% and facilitated true skin regeneration with hair follicles and sebaceous glands. Furthermore, the SMART patch reshaped the wound microenvironment by enhancing M2 macrophage polarization and reducing oxidative stress. Transcriptomic analysis and verification of the protein expression levels indicated upregulation of yes-associated protein (YAP) and nuclear factor erythroid 2-related factor 2 (Nfr2) pathways involved in extracellular matrix remodeling, immune modulation, and cellular proliferation. This study introduces a combined mechano-chemical delivery system that addresses key limitations in diabetic wound healing, offering a promising controlled-release platform for regenerative therapy.

Objectives: Critical-sized bone defects continue to represent a substantial challenge in orthopedic clinical practice. Decellularized bone matrix (DBM) possesses favorable osteoconductive properties due to its retention of native extracellular matrix architecture and collagen components. However, its limited osteogenic bioactivity restricts its application in complex bone defect repair. This study aimed to construct a dendritic mesoporous silica (DMSN)-modified DBM composite scaffold loaded with teriparatide (DBM-DMSN@TPTD) and to systematically evaluate its physicochemical properties, drug release behavior, biocompatibility, and osteogenic differentiation-promoting capacity. Methods: A DBM scaffold was prepared from bovine femoral cancellous bone via a combined freeze–thaw and chemical detergent decellularization method. DMSNs were synthesized through a sol–gel method, amine-functionalized with APTES, and covalently grafted onto the DBM surface via EDC/NHS crosslinking. Teriparatide was loaded onto the composite scaffolds at three concentrations (1, 10, and 100 nmol/L). The scaffolds were characterized via SEM, TEM, BET, EDS and XPS. Decellularization efficacy was assessed by DAPI staining and nucleic acid quantification. Drug release behavior was evaluated through in vitro release studies, while biocompatibility and osteogenic differentiation of rat BMSCs were examined using Live/Dead staining, phalloidin/DAPI cytoskeletal staining, CCK-8 assays, ALP staining, and RUNX2/OCN immunofluorescence. Results: DMSNs demonstrated a dendritic mesoporous architecture, featuring a specific surface area of 390.44 ± 1.78 m2/g and pore diameters within the range of 15–20 nm. DBM showed effective removal of immunogenicity, with well-preserved collagen architecture. Drug release displayed a biphasic pattern, with 56.03% released within the first 72 h and 83.23% by day 16. None of the tested scaffolds showed obvious cytotoxicity under the experimental conditions. The DBM-DMSN@TPTD-M group (10 nmol/L) produced the strongest effects on BMSC proliferation and osteogenic differentiation, as indicated by the highest ALP activity and elevated RUNX2 and OCN expression (p < 0.05). Conclusions: The DBM-DMSN@TPTD scaffold offers a native bone microenvironment, sustained drug release, and osteogenic activity in vitro. These features may support BMSC proliferation and osteogenic differentiation. Accordingly, this scaffold warrants further investigation as a potential strategy for bone defect repair.

Mesenchymal stem cells (MSCs) possess immunomodulatory properties and are concurrently influenced by the local inflammatory microenvironment. Extracellular vesicles (EVs) derived from MSCs (MSCs-EVs) replicate the therapeutic effects of their parent cells while avoiding the limitations of cell therapy. Elucidating the impact of diverse inflammatory factors on the composition and functionality of MSCs-EVs is crucial for their optimal use, though this remains incompletely understood. The aim of this study was to explore the immunomodulatory effects and underlying mechanisms of EVs derived from adipose-derived stem cells (ADSCs) pretreated with TNF-α and TGF-β1 (α-EVs and β-EVs) on macrophages and tissue-engineered cartilage regeneration. Isolation and identification of EVs from ADSCs cultured in 3D spheres. The effects on chondrocyte and macrophage proliferation, migration, and polarization were evaluated in vitro. In vivo, chondrocytes-laden porous GelMA hydrogel with EVs were implanted into mice to assess chondrocyte regeneration and macrophage infiltration. Small RNA sequencing revealed distinct EVs-miRNA expression profiles, and the target validation confirmed the molecular mechanism. In vitro, both α-EVs and β-EVs demonstrated the capacity to modulate macrophage phenotypes. α-EVs more effectively reduced M1 macrophage markers and enhanced M2 polarization. Besides, β-EVs exhibited a stronger inhibitory effect on macrophage proliferation and migration, while also promoting chondrocyte proliferation and extracellular matrix (ECM) formation. In vivo, β-EVs significantly improved ECM deposition and chondrocyte maintenance, while both EVs groups reduced M1 infiltration and increased M2 presence. Small RNA sequencing identified miR-378a-3p upregulation in both α-EVs and β-EVs, targeting Signal-regulatory protein alpha (SIRPα) to modulate the immune status of macrophages. Both TNF-α and TGF-β1 enhanced the immunomodulatory effects of EVs, with TGF-β1 showing a stronger capacity to promote chondrocyte proliferation and ECM synthesis. The miR-378a-3p/SIRPα axis was identified as a key mechanism underlying the protective effects of both α-EVs and β-EVs. This study provides valuable insights into optimizing EVs-based regenerative strategies to regulate the local inflammatory microenvironment and promote the regeneration of engineered tissues.

Natural antioxidant enzymes play a central role in regulating oxidative stress within living organisms. During tissue repair following injury, these enzymes act synergistically to scavenge excess reactive oxygen species and maintain cellular redox homeostasis, thereby supporting cell proliferation and differentiation, resolving inflammation, and facilitating extracellular matrix remodeling. Inspired by the catalytic properties and regulatory mechanisms of natural antioxidant enzyme systems, antioxidant nanozymes are artificial catalytic nanomaterials that mimic the activity of natural antioxidant enzymes and have emerged as a promising platform to overcome the limitations of natural enzymes and promote tissue regeneration. This review systematically summarizes the classification and catalytic mechanisms of antioxidant nanozymes, along with mechanism-guided design strategies. We further highlight recent advances in their application in regenerative medicine, including skin wound healing, cardiovascular repair, cartilage regeneration, neural tissue repair, bone tissue regeneration, and ocular repair. Finally, the challenges and future prospects of antioxidant nanozymes in regenerative medicine are discussed.

Stress shielding caused by metal implants may result in implant failure due to the mismatched mechanical properties between metal implants and bone. Meanwhile the bio-inertia nature of metal implants often leads to poor osseointegration. Herein, a triply-bioinspired strategy called ‘topology-micromorphology-component-trio’ is proposed to solve these two problems and to enable metal implants for drug delivery. First, to mimic the topology of spongy bone tissues, Ti-6Al-4V (TC4) scaffolds of Triply Periodic Minimal Surfaces (TPMS) lattices (Gyroid, Split-P and Schwarz) and strut-based lattices (Weaire Phelan and Diamond) were designed with Large (L) and Small (S) pores and manufactured by 3D printing. Second, various alkaline treatments were tested on TC4 to achieve a micromorphology with microfibers resembling blood clots. Third, an injectable hydrogel mimicking extracellular matrix components was infused into porous TC4 scaffolds. It was then photo-crosslinked to obtain TC4 scaffolds with interpenetrating Double Network (DN) hydrogel. Overall, the L-Gyroid lattice of TPMS shows superior 3D-printing manufacturability, mechanical properties, and cytocompatibility than the others. The alkaline treatment condition of 16.6 wt

Despite significant progress in repairing osteochondral injuries using 3D printing technology, most cartilage layer scaffolds are made of degradable materials, making it difficult to simultaneously provide extracellular matrix functionality while replicating the mechanical properties of natural cartilage layers. Additionally, their degradation rate is challenging to align with cartilage regeneration. Furthermore, double-layer scaffolds commonly used for repairing osteochondral often exhibit inadequate bonding between the cartilage layer scaffolds and bone layer scaffolds. To solve these problems, we presented a bilayer scaffold composed of a 3D printed non-degradable thermoplastic polyurethane (TPU) scaffold filled with hydrogel (Gel) made of gelatin and sodium alginate as the cartilage layer (noted as TPU/Gel), meanwhile, a 3D printed polylactic acid (PLA) scaffold containing 10 % hydroxyapatite (HA) as the bone layer (noted as PLA/HA). At the junction of the bone layer and cartilage layer, TPU tightly bonded with the bone layer scaffold under high temperatures. The hydrogel filling within the TPU layer of cartilage served not only to lubricate the joint surface but also aided in creating a 3D microenvironment. The non-degradable nature of TPU allowed the cartilage layer scaffold to seamlessly integrate with the surrounding regenerated cartilage, achieving permanent replacement and providing shock absorption and weight-bearing effects. This effectively addressed the mechanical challenges associated with cartilage regeneration and resolved the inconsistency between cartilage regeneration and material degradation rates.

Medical implants of exogenous materials often induce foreign body response (FBR) in hosts, which is characterized by inflammation and fibrosis. Herein, composite scaffolds with interpenetrating hard and soft phases were fabricated, consisting of titanium alloy and a biomatrix mimicking extracellular matrix. Spermidine-functionalized biomatrix (CST@GOA) not only inhibits inflammatory response and osteoclastogenesis of macrophages, but also fosters migration and osteogenesis of MC3T3-E1 cells. Interestingly, CST@GOA can mitigate acute inflammation and fibrosis, characteristics of FBR, against silicone implanted in rats. Moreover, bone repair experiments in rabbits show that CST@GOA-interpenetrated porous titanium alloy scaffolds attenuate FBR against metal implants and promote osseointegration. Meanwhile, diethylenetriamine, a polyamine resembling spermidine in chemistry, has been used in place of spermidine to enable ‘operando’ comparison in both cell and animal experiments. Proteomic analysis of rabbit bone tissues reveals that spermidine modulates PI3K-Akt pathway by upregulating PTEN, which may play a pivotal role in coordinating downstream signaling of inflammation, autophagy and bone homeostasis. Together, it is demonstrated that spermidine can endow either synthetic polymers or metal implants with anti-FBR activity by regulating host response and nurture peri-implant niche to improve osseointegration of metal implants. Hence, spermidine affords a natural and elegant strategy to alleviate FBR against medical implants.

Inadequate osseointegration remains a major clinical challenge in joint replacement surgery, frequently resulting in aseptic loosening and necessitating revision procedures. Herein, we present a novel approach that combines 3D printing, tissue engineering, and biomimetic technologies to address this problem. We developed a novel surface modification strategy to engineer two functional interfaces on microporous titanium implants (PTi): an intrafibrillar/extrafibrillar mineralized collagen interface (I-EMC/PTi) and an extrafibrillar mineralized collagen interface (EMC/PTi). The fabrication process involves dopamine self-polymerization, covalent collagen immobilization, and subsequent biomineralization through ion-mediated crystallization and polymer-induced liquid-precursor techniques. This hierarchical method achieves comprehensive functionalization of the microporous titanium surface. The engineered hybrid interfaces markedly improved the surface properties of PTi, including roughness, hydrophilicity, and protein adsorption capacity. Notably, the I-EMC/PTi interface exhibited nanostructural features resembling natural bone tissue and optimal surface roughness, demonstrating superior osteoinductive properties. Moreover, this interface modulates the bone immune microenvironment by promoting M2 macrophage polarization, thereby enhancing osteogenic differentiation of bone marrow mesenchymal stem cells. In vivo evaluation using a rabbit femoral condyle defect model confirmed that the I-EMC/PTi implant significantly promoted new bone formation and improved bone-implant integration, as quantitatively confirmed through micro-computed tomography and histological analyses. Overall, this study provides a promising strategy for constructing artificial implants with enhanced bioactivity and establishes a robust foundation for developing next-generation implant materials with enhanced clinical performance.

Rationale: Bilateral gluteus medius contractures in adults are rare in clinical practice, with only a few cases reported. These contractures may result from repeated intramuscular injections during childhood. Understanding the clinical manifestations, diagnostic process, treatment, and outcomes can provide insights into effective management strategies. Patient concerns: A 28-year-old female presented with an abnormal walking posture characterized by an out-toeing gait. She reported long-standing difficulties in walking and sought medical attention to improve her mobility and quality of life. Diagnoses: The patient was diagnosed with bilateral gluteus medius contractures. Interventions: The patient underwent open surgical release of the contractures on both sides, followed by a structured rehabilitation program to restore muscle function and improve gait. Postoperative exercise guidance was provided to ensure optimal recovery. Outcomes: At the 1-year follow-up, the patient demonstrated significant improvement in gait, functional abilities, and overall quality of life. She expressed high satisfaction with the surgical and rehabilitative outcomes. Lessons: Once diagnosed with gluteus medius contracture, early surgical intervention is recommended. Through case reports and literature review, we have summarized the etiology, diagnostic methods, clinical characteristics, and existing treatment options for this condition.

Periodontitis is a chronic inflammatory condition affecting the periodontal tissue. This condition worsens in diabetic patients due to oxidative stress and inflammation. Herein, we investigated a treatment using bioactive Zn-V-Si-Ca glass nanoparticle hydrogel microneedles. The microneedles contain bioactive glass nanoparticles codoped with zinc and vanadium ions. They also include gallic acid and oxidized methacrylated hyaluronic acid. These microneedles address bacterial dysbiosis and oxidative stress in diabetic periodontitis. They provide antibacterial and antioxidant effects. The microneedles deliver therapeutic agents directly into the gingival tissue. This enhances drug retention and absorption by penetrating the mucosal barrier. In vitro studies demonstrated biocompatibility, excellent antioxidant properties, and acceptable mechanical properties. Meanwhile, the microneedle patches demonstrated antibacterial properties effective against a Gram-negative periodontal pathogen as well as a Gram-positive oral bacterium. In vivo experiments were performed using a diabetic rat model with periodontitis. Results showed significant improvement in alveolar bone regeneration. The hydrogel modulated the inflammatory microenvironment effectively. Ribonucleic acid sequencing revealed downregulation of JAK-STAT and NF-kappa B inflammation signaling pathways. This work presents a distinctive approach to suppressing the inflammatory response and modulate immune responses for the purpose of treating diabetic periodontitis early.

The RNA found in the circular system is known as extracellular RNA (exRNA). This kind of RNA has been found to play a biological role similar to that of a messenger. They can be used as indicators of disease status or the physiological health of an organism. A large number of RNA-based biomaterials have been developed by simulating the biological function and structure of natural RNA molecules. The structural programmability of RNA-based biomaterials provides the spur for scientists to pioneer new approaches in disease detection and prevention. Nevertheless, the link between exRNA function and the design of RNA-based biomaterials has not been fully understood. Understanding the biological structure and function of exRNA will contribute to the clinical translation of this novel biotechnology. The present review discusses the research progress associated with exRNA and their derivatives to bridge the gap between natural exRNA and RNA-based biomaterials.

Purpose:To evaluate whether the joint function, stability and safety of tibial supplementary fixation in anterior cruciate ligament reconstruction is superior compared with tibial screw fixation alone. Methods:PubMed, Cochrane Library, EMBASE and Web of Science were searched, tracking until 12 April 2025. Eligible studies included published randomized controlled trials (RCTs) and low-risk cohort studies comparing clinical outcomes and complications between tibial screw interference with supplementary fixation (Group I) and tibial screw interference alone or with a sheath (Group II). RCTs were assessed using the Cochrane Risk of Bias tool, while cohort studies were evaluated with the Newcastle-Ottawa Scale and Methodological index for non-randomized studies. Model selection (random or fixed-effects) was based on data heterogeneity. Results:This meta-analysis included eight studies with 943 patients (Group I: 386, Group II: 557). Group I showed no significant differences in side-to-side difference (SSD) in the sheath subgroup at 24 months, SSD <3 mm at 9.1 kg at 12 and 24 months, or manual maximum testing at 24 months, Pivot test at 8-12 and 24 months, Lachman test at 8-12 months, International Knee Documentation Committee objective and subjective score at 24 months compared to Group II. Group I demonstrated statistically significant reductions in SSD (mean difference: -1.02; 95% CI: -1.79 to -0.25; p = 0.009) in the no-sheath subgroup and lower Lachman test positivity (odds ratio [OR] = 0.30; 95% confidence interval [CI]: 0.13-0.71; p = 0.01) at 24 months. Ligament retear rates were similar; however, Group I experienced a substantially higher incidence of kneeling pain (OR = 6.28; 95% CI: 1.86-2.25; p < 0.01), an outcome that could adversely affect patient comfort and long-term functional recovery. Conclusion:Enhanced supplementary tibial fixation with soft tissue autografts and allografts offers similar joint function and a modest enhancement of stability compared to tibial interference screw fixation alone, but is associated with a higher incidence of pain. Level of Evidence:Level III, retrospective cohort studies have been analysed, alongside RCTs, and thus this is the level of evidence.

Clinically, intraoperative treatment of bone tumors presents several challenges, including the effective inactivation of tumors and filling of irregular bone defects after tumor removal. In this study, intelligent thermosensitive composite materials with shape-memory properties were constructed using polylactic acid (PLA) and polycaprolactone (PCL), which have excellent biocompatibility and degradability. Additionally, beta-tricalcium phosphate (β-TCP), with its osteogenic properties, and magnesium (Mg) powder, with its photothermal and bone-promoting abilities, were incorporated to improve the osteogenic potential of the composite and enable the material to respond intelligently to near-infrared (NIR) light. Utilizing 3D printing technology, the composite material was prepared into an NIR-responsive shape-memory bone-filling implant that deforms when the scaffold temperature increases to 48 ℃ under NIR laser irradiation. Moreover, at a lower temperature of 42 ℃, mild photothermal therapy promotes macrophage polarization toward the M2 phenotype. This process regulates the secretion of interleukin (IL)-4, IL-10, tumor necrosis factor-α, IL-6, and bone morphogenetic protein (BMP)-2, reducing local inflammation, enhancing the release of pro-healing factors, and improving osteogenesis. Overall, this innovative scaffold is a promising and efficient treatment for filling irregular bone defects after bone tumor surgery.

Background: Immunometabolism, the regulation of immune cell function through metabolic pathways, has emerged as a key focus in regenerative medicine. Traditional bone healing therapies primarily target the osteoblast–osteoclast regulatory axis, overlooking the metabolic reprogramming of immune cells (e.g., macrophages) and limiting regenerative efficiency. Macrophages orchestrate bone healing through dynamic shifts between proinflammatory (M1-like) and reparative (M2-like) metabolic phenotypes. Recent studies have shown that their immunometabolic transitions govern the sequential phases of bone healing. Therefore, targeting macrophage immunometabolism may offer a novel therapeutic paradigm for bone regeneration. Aim of review: This review summarizes recent advances in understanding how macrophage metabolism regulates bone healing, emphasizing the critical role of immunometabolism in resolving inflammation and regenerating tissue throughout the repair process. By integrating insights from the fields of cellular metabolism, microenvironmental signals, and biomaterial science, this review aims to offer an integrative perspective on how targeting macrophage metabolic control could serve as a therapeutic strategy to enhance bone regeneration. Key scientific concepts of review: This review addresses five core concepts. First, it delineates the spatiotemporal roles and phenotypic shifts of macrophages in the different phases of bone healing. Second, it explores how the reprogrammed metabolism of glucose, lipids, and amino acids underlies macrophage polarization and function. Third, it emphasizes how microenvironmental cues, including cytokines, metabolic intermediates, and microbiota-derived metabolites, modulate macrophage immunometabolism. Fourth, it summarizes emerging therapeutic strategies designed to regulate macrophage metabolism for bone regeneration, such as cell-based therapies, immunomodulatory hydrogels, and nanotechnologies. Finally, it identifies major challenges in this field. These include the temporal–spatial complexity of immunometabolism, the lack of human-relevant models, the emerging concepts of cross-system regulation, and the technological limitations in targeted regulation. Together, these insights provide a conceptual basis for future precision immunometabolic interventions in bone repair.

Maxillofacial bone repair demands implants that match native mechanics, yet conventional designs struggle to balance strength and toughness. We present an interpenetrating phase composite (IPC) that couples a PLA lattice with a PETG network, printed via multimaterial FDM into P-type TPMS architectures with offset thickness d = 0.4-1.2 mm. The IPC shows a synergistic "1 + 1 > 2" effect: versus porous PLA, compressive strength increases by 153-244 %. Finite-element analysis reveals more uniform stress fields and delayed local buckling under compression. A modified dual-phase Gibson-Ashby model predicts elastic modulus and yield strength across densities and compositions, with good agreement to experiments. Calcein-AM/PI and CCK-8 assays indicate high cell viability and negligible cytotoxicity. ALP activity and Alizarin Red staining support preserved osteogenic potential, while short-term subcutaneous implantation demonstrates favorable tissue responses with neovascularization and collagen remodeling. Simulated body-fluid immersion shows composition-dependent, predictable hydrolytic behavior. Collectively, the rigid-flexible coupling of PLA/PETG IPC TPMS structures yields concurrent gains in strength, toughness, and energy absorption with reassuring biosafety, positioning this platform as a promising option for load-bearing, patient-specific craniofacial implants and offering a practical framework for performance prediction and design optimization.

Deer antlers, the only mammalian bony organs capable of complete regeneration, exhibit a growth rate of 2.7 cm/day, far surpassing human long bones (1 mm/day). Long-bone critical defects (LBCDs) occur when defects exceed intrinsic healing capacity. While antler stem cells drive regeneration, their immunogenicity limits clinical translation. Antler extracellular matrix (ECM) components have been proven to enhance bone repair, the role of its unique "longitudinal tubule-transverse connection" structure remains unexplored. Here, matrix scaffolds (devoid of cellular/active components) were prepared along longitudinal (L) or horizontal (H) axes, with cancellous scaffolds (R) as controls. Histological and in vitro analyses confirmed structural integrity and immunogenicity elimination. Bone marrow mesenchymal stem cells (BMSCs) exhibited structural guidance in morphology and migration on L. Ectopic implantation revealed no intrinsic osteogenic activity but demonstrated robust alignment of soft tissues along scaffold scaffolds. In rat femoral segmental defect models, L induced significantly greater depth and volume of oriented new bone (vs. H or R) while effectively blocking fibrous encapsulation. This study identifies antler-specific structural topology-rather than cellular or biochemical factors-as the critical osteoconductive driver enabling rapid bone regeneration. The findings establish a proof-of-concept for bioinspired structural designs in addressing LBCDs, providing guidance for the development of antler-derived bone replacement implants and biomimetic design of additive manufacturing implants.

Small extracellular vesicles (sEVs) are cell-derived particles used for intercellular communication in living organisms that have gained great interest from researchers for their use as drug carriers and diagnostic agents. However, the isolation and storage of sEVs lead to issues including lipid membrane disruption, protein denaturation, and nucleic acid degradation. Herein, a surface functionalization strategy is reported for encapsulating single sEV into selectively disassemblable protective shells composed of metal-phenolic networks (MPNs) post-modified with poly(ethylene glycol) (PEG). Disassemblable MPN shells can be rapidly deposited on sEVs in a one-step manner and post-modified with PEG. These coatings enhance the colloidal stability of sEVs and protect them against harsh storage conditions, while the non-covalent and selectively disassemblable nature of the MPN shell allows recovery after storage without compromising their surface integrity and functionality. It is demonstrated that various triggers, such as pH adjustment, competitive chelation, and redox reactions, can be used to disassemble the MPN shell, thereby offering widely adoptable strategies depending on the target applications. This approach potentially overcomes conventional challenges associated with sEV processing and storage and may contribute to reducing cold-chain requirements and transportation costs of future sEVs-based therapeutics and diagnostics.