Xiao Yang

Sustained baicalin release from mesoporous silica nanoparticles (MSNs) promotes macrophage M2 polarization via PI3K/AKT/GSK3β signaling, creating an immune-instructive microenvironment for enhanced cutaneous wound healing.

Osteoporotic bone defects remain a major clinical challenge due to impaired osteogenesis, disrupted angiogenesis, and poor scaffold integration. To overcome these limitations, we developed hierarchical micro-/nanostructured hydroxyapatite (nwHA) scaffolds by integrating morphology-specific nanohydroxyapatite (nHA) onto whisker-reinforced hydroxyapatite (wHA) scaffolds. This modular strategy decouples mechanical strength from interfacial bioactivity, enabling programmable topographical control. Five distinct nHA morphologies were used to functionalize wHA scaffolds, which were systematically evaluated both in vitro and in osteoporotic rat models. Among them, nanofiber-coated scaffolds (nwHA1) significantly enhanced bone volume fraction, mineral apposition rate, mechanical strength, and neovascularization. Histological analysis identified three distinct ossification patterns—type I (wall-penetrating), type II (surface-appositional), and a hybrid endochondral–intramembranous mode—whose distribution varied with nHA morphology and the local microenvironment. Mechanistically, nwHA1 activated canonical Hedgehog signaling and upregulated HIF-1α in both MSCs and HUVECs, thereby promoting coordinated osteogenic and angiogenic responses. Pharmacological inhibition with cyclopamine, as well as siRNA-mediated knockdown of GLI1 or HIF-1α, significantly attenuated these pro-osteoangiogenic markers, confirming functional crosstalk between Hedgehog and hypoxia signaling pathways in response to scaffold-induced topographic cues. These findings establish nHA morphology as a critical topographical regulator of bone regeneration and provide a versatile platform for designing adaptive bioceramics tailored to osteoporotic bone repair.

Beta‐tricalcium phosphate (TCP) bioceramic is a widely used artificial bone substitute, but its rapid degradation and inflammatory activation inhibit complete bone healing. Here, we synthesize a novel lignin‐incorporated polyurethane (LPP) exhibiting a temperature‐induced sol–gel transition, which can form a hydrogel at body temperature. This copolymer is further applied as a dual‐functional coating onto TCP porous scaffolds for bone tissue engineering. Our results demonstrate that the polyurethane coating effectively delays the degradation of TCP both in vitro and in vivo. The incorporation of lignin endows the polyurethane backbone with the capacity to reduce immune cell infiltration and promote neovascularization, thus enhancing the osteoinduction in TCP. For the implantation of in vivo femoral defects, the TCP‐LPP scaffold achieves satisfactory bone regeneration, which is attributed to moderate degradation rate, enhanced osteoinductivity, and upregulation of N6‐methyladenosine methylation. In summary, a new strategy of lignin coating with intrinsic antioxidant activity is developed to optimize the regenerative outcomes of TCP bone substitutes.

Implant‐associated infections present a major clinical challenge, as orthopedic implants are required to both suppress bacterial infection and support subsequent bone regeneration. Herein, a mechanically adaptive auxetic titanium scaffold integrated with a lattice‐modulated piezocatalytic coating is developed for infected bone repair. A titanium scaffold with a negative Poisson's ratio structure demonstrates uniform stress distribution under compression. It prolongs fluid residence time by creating complex flow paths, which is favorable for interaction with surrounding bone tissue. Additionally, a potassium sodium niobate (KNN) piezoelectric coating with strontium (Sr) incorporated as a lattice dopant is constructed on the scaffold surface. Strontium doping restructures the electromechanical landscape of KNN, amplifying its piezoelectric response and piezocatalytic reactivity, which underpins potent antibacterial efficacy. Concurrently, the osteogenic bioactivity imparted by Sr enables robust osseointegration and bone regeneration. In a rabbit femoral condyle infected bone defect repairment, the piezo‐coated auxetic scaffold achieves suppression of local infection and inflammation after 1 week of ultrasound treatment. Subsequently, enhanced osseointegration and bone regeneration are observed, accompanied by improved hindlimb strength and motor coordination. This work establishes a multifunctional implant paradigm that couples mechanical adaptation with lattice‐modulated piezocatalysis, enabling synergistic infection eradication and bone regeneration.

Osteochondral defects remain difficult to repair because articular cartilage and subchondral bone differ in structure and regenerative capacity, and stable interface integration is challenging. Here, we developed a structurally continuous yet functionally stratified biphasic scaffold via dual-temperature 3D printing, consisting of a poly(ε-caprolac tone)/β-tricalcium phosphate (PCL/β-TCP) bone-mimetic phase with larger macropores and a pure PCL cartilage-guiding phase with smaller pores. A GelMA/chondroitin sulfate (GelMA/CS) hydrogel was selectively infiltrated into the upper region by immersion and photocrosslinking, while a ∼0.5 mm hydrogel-free transitional zone was preserved as a structural transition region between the chondral hydrogel compartment and the subchondral scaffold. In vitro, GelMA/CS functionalization enhanced chondrocyte adhesion, promoted sGAG secretion and upregulated chondrogenic genes. Under osteochondral induction, the scaffolds supported osteo- and chondrogenic marker expression in human umbilical cord-derived mesenchymal stem cells. Transcriptomic profiling indicated enrichment of ECM- and mechanotransduction-related pathways, consistent with the involvement of TRPV4-associated mechanosensing and PI3K/AKT-related signaling. In a rabbit femoral osteochondral defect model, the GelMA/CS-functionalized scaffold enhanced early subchondral bone regeneration by micro-CT and promoted cartilage-like matrix deposition and chondrogenic marker staining compared with the unmodified scaffold and untreated control at 4 and 8 weeks. This hydrogel-integrated biphasic design offers a scalable strategy for coordinated osteochondral regeneration.

Background: The effect of tourniquet use on cement penetration in primary total knee arthroplasty (TKA) remains controversial. Current assessments rely primarily on radiograph-based 2D measurements, which limit the precision and comprehensiveness of analysis. Therefore, this study investigated the effect of tourniquet use on 3D cement penetration and the association of tourniquet use with mid-term implant stability. Methods: In this prospective randomized controlled trial, 141 Han Chinese (East Asian) patients (mean age, 68.3 years; 85% female) were allocated to 1 of 3 groups: tourniquet (Group A), no tourniquet (Group B), and tourniquet during cementation only (Group C). The primary outcomes were 3D cement penetration (thickness, volume, surface area) and mid-term implant stability assessed on the basis of radiolucent lines (RLLs) and survivorship. Cement penetration metrics across femoral and tibial components were systematically quantified through 3D morphological analysis of metal artifact reduction-computed tomography (MAR-CT) images reconstructed using Avizo software (Thermo Fisher Scientific). Secondary outcomes included blood loss, inflammatory and muscle-injury biomarkers, pain scores, functional scores, postoperative length of stay, and complication rates. Results: All participants were followed for 5 years. No significant intergroup differences in cement penetration (thickness, volume, surface area) around the tibial (p = 0.847, p = 0.473, and p = 0.395, respectively) and femoral (p = 0.203, 0.201, 0.399) components were observed. Cement thickness correlated with preoperative knee deformity but not with implant size. Additionally, Group B demonstrated superior clinical outcomes versus Groups A and C: lower levels of inflammatory and muscle-injury biomarkers, lower early pain scores, and a shorter hospital stay, with enhanced 3-month knee function demonstrated in Groups B and C versus Group A. Total blood loss, mid-term outcomes, and complication rates were comparable. No RLLs or revisions were observed, and the 5-year implant survival rate was 100%. Conclusions: Tourniquet use showed no significant effect on cement penetration and mid-term implant stability in primary TKA, and omitting intraoperative tourniquet use was associated with better early postoperative functional recovery in patients undergoing TKA. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Repairing jawbone defects remains a clinical challenge due to the limited adaptability and regenerative capacity of conventional grafts. In this study, we designed an osteoinductive and piezoelectric composite for jawbone repair which possessed a plasticine-like texture, termed as "osteoplasticine." This material combines a stereocomplex of poly(l/d)-lactic acid and a poly(ε-caprolactone) network, imparting thermoplasticity and enabling uniform dispersion of two functional ceramic nanoparticles. Nanosized hydroxyapatite particles provide bone-forming capability, while the nanopotassium sodium niobate particles promote osteogenic differentiation and metabolic activity through piezoelectric cues upon mechanical loading or ultrasound stimulation. The osteoplasticine we synthesized exhibits good moldability when heated above physiological temperature and elicits measurable electrical signals when used. Leopard-spotted pattern osteogenesis was observed in the osteoplasticine group at both osseous and nonosseous implantation sites. Abundant bone regenerating nodules (∼55 μm) were found in the central region of the material. The local renin-angiotensin-aldosterone system is involved in this process. This work presents a moldable and piezoelectrically responsive bone graft material that shows potential for future integration with noninvasive stimulation strategies to repair complex maxillofacial bone defects.

Objectives: Pelvic reconstruction with conventional 3D‐printed prostheses faces a critical trade‐off, where achieving sufficient porosity for optimal bone ingrowth often compromises essential mechanical stability. To address this challenge, this study evaluates the clinical outcomes of 3D‐printed hemipelvic prostheses incorporating re‐entrant chiral structure (RCS), a novel negative Poisson's ratio design, in patients undergoing pelvic reconstruction following tumor resection. Methods: A retrospective analysis was conducted on 15 patients (eight females and seven males; mean age: 39.3 ± 11.7 years) with pelvic malignancies who underwent reconstruction using 3D‐printed hemipelvic prostheses incorporating RCS between March 2018 and June 2023. The diagnoses included osteosarcoma ( n = 8), Ewing's sarcoma ( n = 3), chondrosarcoma ( n = 2), and high‐grade soft tissue sarcoma ( n = 2). All patients were staged as IIB according to the Enneking system, except for one case of Ewing's sarcoma (stage III). Neoadjuvant chemotherapy (four cycles) was administered to six osteosarcoma patients, and one Ewing's sarcoma patient received six cycles, while other patients proceeded directly to surgery. Patient outcomes were systematically evaluated through oncological status, functional performance (MSTS‐93 score), pain assessment (VAS score), surgical parameters, complications, and radiographic analysis using Tomosynthesis Shimadzu Metal Artifact Reduction Technology (T‐SMART). Results: At the latest follow‐up (44.5 ± 9.4 months), 13 patients (86.7%) remained disease‐free; one patient (6.7%) experienced local recurrence requiring revision surgery, and one patient (6.7%) died of metastatic complications at 32 months post‐surgery. Functional outcomes showed significant improvement, with mean MSTS‐93 scores increasing from 14.5 ± 1.1 preoperatively to 25.8 ± 1.3 at final follow‐up ( p < 0.001). Pain control was satisfactory, with VAS scores decreasing from 5.5 ± 0.6 to 1.5 ± 0.5 ( p < 0.001). The mean surgical duration was 289.3 ± 30.4 min, with an average intraoperative blood loss of 3540 ± 621.5 mL. Early complications included delayed wound healing in three cases (20%), successfully managed with wound care protocols and VAC therapy. One patient (6.7%) developed deep prosthetic infection at 14 months post‐surgery, necessitating a two‐stage revision procedure. No mechanical failures, aseptic loosening, or prosthesis fractures were observed during the follow‐up period. Radiographic analysis demonstrated progressive bone ingrowth into the RCS porous regions in all cases, with no signs of osteolysis or implant migration in the remaining prostheses. Conclusion: D‐printed custom hemipelvic prostheses with RCS offer an effective solution for pelvic reconstruction by achieving an optimal balance between mechanical stability and biological integration, leading to promising clinical outcomes.

Recent studies have revealed a great diversity and complexity in extracellular vesicles and particles (EVPs). The developments in techniques and the growing awareness of the particle heterogeneity have spurred active research on new particle subsets. Latest discoveries highlighted unique features and roles of non-vesicular extracellular nanoparticles (NVEPs) as promising biomarkers and targets for diseases. These nanoparticles are distinct from extracellular vesicles (EVs) in terms of their smaller particle sizes and lack of a bilayer membrane structure and they are enriched with diverse bioactive molecules particularly proteins and RNAs, which are widely reported to be delivered and packaged in exosomes. This review is focused on the two recently identified membraneless NVEPs, exomeres and supermeres, to provide an overview of their biogenesis and contents, particularly those bioactive substances linked to their bio-properties. This review also explains the concepts and characteristics of these nanoparticles, to compare them with other EVPs, especially EVs, as well as to discuss their isolation and identification methods, research interests, potential clinical applications and open questions.