Peifu Tang

Achieving efficient bone repair necessitates a thorough understanding of the physiological activities of native bone tissue, enabling selection and design of appropriate materials. To date, artificial scaffolds have been developed from inert materials to bioactive materials and demonstrate the capabilities to promote bone repair. However, the complex physiological changes that occur during bone repair pose significant challenges to their practical clinical applications. In this Review, we summarize the studies of bone biology and the evolution of materials design in the context of bone‐tissue engineering applications. Specifically, we emphasize the role of biomaterials from a materials science perspective in regulating cell fates. Furthermore, we introduce the concept of programmable bio‐interactive materials as a potential solution for bone regeneration. These materials possess the ability to dynamically and precisely interact with biological systems, guiding the bone‐tissue regeneration process. Additionally, we discuss the unmet needs and current challenges faced in the development of bio‐interactive materials for bone‐tissue regeneration. By highlighting emerging strategies in the field, we aim to shed light on future directions for research and development in this exciting area of study.

Neural innervation is of vital importance for muscle mass and function, and denervation induces progressive muscle atrophy, which lacks effective treatments. Polyamine metabolism is reported to be innervation responsive and involved in denervation‐induced muscle atrophy, yet the effects of polyamine in denervated muscle atrophy remain unknown. In this study, using a sciatic nerve transection model, we observed progressive increases in putrescine and spermidine, alongside induction of polyamine metabolism enzymes, coincident with the early rapid atrophy phase post denervation. Pharmacological ODC1 inhibition lowered intramuscular polyamines and improved denervated muscle atrophy and fibrosis. In contrast, spermidine supplementation induced muscle atrophy and atrogene expression in healthy and denervated muscle, implicating spermidine as a pro‐atrophic metabolite. Single‐nucleus sequencing revealed an expansion of atrophic myonuclei and depletion of type IIb myonuclei post denervation. DFMO reduced the atrophic myonuclear fraction, increased MuSCs abundance, and suppressed FAPs derived FGF signalling dominated by the Fgf7‐Fgfr2 axis to maintain MuSCs homeostasis. Taken together, our results demonstrate that dysregulated polyamine metabolism is a key contributor to denervation‐induced muscle atrophy, and ODC1 inhibition mitigates muscle atrophy and fibrosis by restraining proteolysis and preserving MuSCs homeostasis, which will provide references for future clinical treatments.

Objective: Hip fracture causes significant morbidity and mortality, necessitating the identification of biomarkers for risk stratification. This study aimed to evaluate the association between N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and incidence of postoperative complications and the 2‐year all‐cause mortality among hip fracture patients. Methods: This retrospective cohort study involved 2595 patients aged from 45 years who received surgery for hip fracture between 2000 and 2022. Preoperative NT‐proBNP levels were used to divide patients into three groups: low (< 123.27 pg/mL), moderate (123.27–349.93 pg/mL), and high (> 349.93 pg/mL) NT‐proBNP group. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the odds ratio (OR) for postoperative complications and the hazard ratio (HR) for mortality, after adjusting for potential confounders. Results: Post‐operative complications were reported in 171 (6.59%) patients with mortality of 226 (8.71%) during the 2‐year follow‐up. Compared to patients with low NT‐proBNP group, the adjusted odds ratio for postoperative complications was 1.21 (95% CI 0.69–2.15) for those in the moderate NT‐proBNP group and 2.33 (95% CI 1.35–4.03) for those in the high NT‐proBNP group. Similarly, the adjusted hazard ratio for 2‐year all‐cause mortality was 1.51 (95% CI 0.91–2.50) for those in the moderate NT‐proBNP group and 2.66 (95% CI 1.63–4.32) for those in the high NT‐proBNP group. Higher pre‐operative NT‐proBNP levels were associated with an increased risk for postoperative complications and 2‐year all‐cause mortality (both p for trend < 0.001) among hip fracture patients. The results were consistent across various subgroup and sensitivity analyses. Conclusion: Preoperative NT‐proBNP is strongly associated with both postoperative complications and 2‐year all‐cause mortality among patients received hip fracture surgery. Higher levels of NT‐proBNP before surgery may serve as a useful biomarker for risk stratification and guiding treatment decisions for this patient subpopulation.

The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age‐related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual’s physiological and molecular state, across diverse Chinese cohorts. This Perspective outlines the core objectives, methodological framework and key deliverables of the X-Age Project, including cohort recruitment, standardized sample collection, multimodal data acquisition and clock model development. By integrating interdisciplinary expertise, we aim to provide a practical and scalable platform for understanding aging complexity and heterogeneity, early detection of accelerated aging and evaluation of aging interventions.

Background: Anteromedial cortex reduction and accurate placement of the cephalomedullary nail is the key point to confront implant failure of intertrochanteric fractures. Existing intramedullary nails cannot compensate for femoral neck‐shaft offset (FNSO), potentially undermining surgical outcome. This study aimed to investigate the effect of FNSO on anteromedial cortex reduction and accurate placement of the cephalomedullary nail for intertrochanteric fractures. Methods: This retrospective study included patients with intertrochanteric fractures treated with short intramedullary nails at our institution from January 2014 to December 2016, who were divided into acceptable and unacceptable groups according to the anteromedial cortex reduction quality. We measured the femoral neck‐shaft offset (FNSO) and offset angle (FNSOA) on the uninjured femur CT. Postoperative CT of the fractured femur was used to measure the offset between the femoral neck axis and the cephalic nail axis (FNCO) and the corresponding angular offset (FNCOA). Cephalic nail insertion alignment was classified into three types (oblique‐forward/rear, coincident, and oblique‐backward/front) based on FNCO/FNCOA values. Group differences were analyzed, and logistic regression identified predictors of poor reduction. Results: Fifty‐seven patients (mean age 78.10 ± 13.47 years; 74% women) were included. The median FNSO and FNSOA of unaffected femurs were 4.31 (IQR 1.50) mm and 4.85° (IQR 2.01). 42.1% of cases had acceptable anteromedial reduction, while 57.9% were unacceptable. Cephalic nail insertion types were: 43.9% oblique‐backward/front, 28.1% coincident, and 28.1% oblique‐forward/rear. The unacceptable reduction group had significantly different FNCO (−2.32 vs. 2.14 mm) and FNCOA (−3.5° vs. 0°) compared to the acceptable group (both p < 0.001), despite similar fracture types and devices. Cephalic nail insertion type differed between groups ( p < 0.001): oblique‐backward/front and coincident insertions were more common in poor reductions. Logistic regression showed that oblique‐backward/front insertion (OR = 51.33, 95% CI 7.60–346.85) and coincident insertion (OR = 9.00, 95% CI 1.52–53.40) were strong independent predictors of unacceptable reduction (both p < 0.001). Among insertion types, oblique‐forward/rear had the lowest median FNCO (3.59 mm) and FNCOA (0.69°) and only 12.5% unacceptable reductions, versus coincident (0 mm, 0°, 56.3%) and oblique‐backward/front (−3.06 mm, −5.84°, 88.0%) ( p < 0.001). Conclusions: It is difficult for existing intramedullary nails to achieve both the reduction of the anterior medial cortex and the accurate implantation of intramedullary nails due to the presence of FNSO. Optimizing intramedullary nailing design and surgical strategy according to FNSO may improve the treatment outcome of intertrochanteric fractures.

Achilles tendon injuries present significant clinical challenges due to limited regenerative capacity and frequent adhesion formation. Here, we report a melatonin-loaded Janus fibrous membrane (MLT@JFM) that mimics the native paratenon's structure and function to promote scarless tendon healing. The biomimetic membrane consists of an inner methacrylated silk fibroin (SFMA) layer that promotes tendon stem cell functions and an outer melatonin-loaded polycaprolactone methacryloyl (PCLMA) layer that prevents adhesion formation. Through photo-cross-linking and structural interlocking, MLT@JFM achieves excellent mechanical properties and stable fixation around injured tendons. In vitro studies demonstrate that MLT@JFM effectively scavenges reactive oxygen species, modulates macrophage polarization, and maintains tendon stem cell phenotype under inflammatory conditions. In a rat Achilles tendon injury model, MLT@JFM significantly enhances functional recovery and biomechanical properties while preventing adhesion formation. Transcriptomic analysis reveals that MLT@JFM promotes scarless healing through synergistic regulation of oxidative-inflammatory cascades and the enhancement of tissue regeneration. This study presents MLT@JFM as a promising therapeutic strategy for tendon repair and provides new insights into biomaterial-mediated tissue regeneration.