Physical cues like morphology, light, electric signal, mechanic signal, magnetic signal, and heat can be used as alternative regulators for expensive but short‐acting growth factors in bone tissue engineering to promote osteogenic differentiation and bone regeneration. As physical stimulation applied directly to the tissue cannot be focused on the bone defect area to regulate the cell behaviors and fate in situ, this limits the efficiency of precise bone regeneration. Biomaterials‐mediated in situ physical cues, as an effective strategy combining the synergistic effect of materials themselves, are put forward and studied widely to promote osteogenic differentiation and bone repair efficiently and precisely. Different types of physical cues provide different choices to better satisfy the requirements for targeted bone defect repair. In this review, the recent research about different biomaterials‐mediated physical cues accelerating osteogenesis in vitro and promoting in situ bone formation in vivo is introduced. Meanwhile, the corresponding possible mechanisms of various physical cues regulating cell responses are also discussed. This review provides useful and enlightening guidance for the utilization of intrinsically physical properties of functional materials to achieve efficient bone regeneration, leading to the design and construction of smart biomaterials for practical applications, and eventually promoting clinical translation.

Materials‐Mediated In Situ Physical Cues for Bone Regeneration

Methicillin‐resistant Staphylococcus aureus (MRSA) is threatening human health due to its resistance to multiple antibiotics. Excessive copper (Cu) ions target the lipoylated proteins of tricarboxylic acid cycle of cancer cells, inducing proteotoxic stress and their cuproptosis death. Whether cuproptosis plays a part in killing MRSA by low‐dose supplement of Cu ions remains to be explored. Herein, Cu‐doped hydroxyapatite nanorods (PC) are prepared on polyetheretherketone (PEEK) to resist infection and improve PEEK performance in tissue integration with the assistance of near‐infrared (NIR) irradiation, and the mechanism against MRSA is elucidated. Mild photothermal stimulation increases bacterial membrane permeability, accelerating Cu ions’ intake and consequently inducing cuproptosis‐like death of MRSA. It is confirmed by aggregation of dihydrolipoamide S‐acetyltrans‐ferase (DLAT), deactivation of glutathione peroxides 4 (GPX4), and destabilization of Fe─S cluster proteins ferredoxin (FDX1) and lipoyl synthase (LIAS). Fortunately, fibroblast behaviors are upregulated on NIR‐irradiated PC. In vivo, PC with NIR irradiation exhibits outstanding MRSA elimination, reduced inflammation response, and improved biointegration. Overall, it is demonstrated that bacterial cuproptosis‐like death can be induced by Cu ions at a non‐cytotoxic dose when cooperated with mild heat stimulus, and this photothermal strategy of PC has greatly promising application in improving PEEK performance in clinic.

Low‐Dose Cu Ions Assisted by Mild Thermal Stimulus Inducing Bacterial Cuproptosis‐Like Death for Antibiosis and Biointegration

In diabetic wound healing, M1 macrophage accumulation and elevated inflammation are prevalent issues. Intelligent delivery systems that can sustainably release antioxidizing and anti-inflammatory ingredients are expected for effective wound healing. Herein, a novel glycyrrhetinic acid (GA) liposomes encapsulated microcapsules delivery system that has desired features for inflammatory wound repair is presented. As the bacteria could break down the alginate shells, the GA liposomes could be controllably released from the microcapsules, which promotes M2 macrophage polarization and regulate their responses in the inflammatory wound microenvironment. Based on these, it is demonstrated that the GA liposomes encapsulated microcapsules delivery system exhibits an anti-inflammatory and immunomodulatory effect for diabetic wound healing in a full-thickness defect model in diabetic rats. These results indicate that the immunomodulatory capabilities of the microcapsules can be unitized for efficient wound repair, and such a delivery system is valuable for clinical wound healing applications. 

Glycyrrhetinic Acid Liposomes Encapsulated Microcapsules from Microfluidic Electrospray for Inflammatory Wound Healing

Surgical resection of bone tumors is the primary approach employed in the treatment of bone cancer. Simultaneously, perioperative interventions, particularly postoperative adjuvant anticancer strategies, play a crucial role in achieving satisfactory therapeutic outcomes. However, the occurrence of postoperative bone tumor recurrence, metastasis, extensive bone defects, and infection are significant risks that can result in unfavorable prognoses or even treatment failure. In recent years, there has been significant progress in the development of biomaterials, leading to the emergence of new treatment options for bone tumor therapy and bone regeneration. This progress report aims to comprehensively analyze the strategic development of unique therapeutic biomaterials with inherent healing properties and bioactive capabilities for bone tissue regeneration. These composite biomaterials, classified into metallic, inorganic non-metallic, and organic types, are thoroughly investigated for their responses to external stimuli such as light or magnetic fields, internal interventions including chemotherapy or catalytic therapy, and combination therapy, as well as their role in bone regeneration. Additionally, an overview of self-healing materials for osteogenesis is provided and their potential applications in combating osteosarcoma and promoting bone formation are explored. Furthermore, the safety concerns of integrated materials and current limitations are addressed, while also discussing the challenges and future prospects. 

Innovative Biomaterials for Bone Tumor Treatment and Regeneration: Tackling Postoperative Challenges and Charting the Path Forward.

Abstract This review highlights recent advancements in the synthesis, processing, properties, and applications of 2D‐material integrated hydrogels, with a focus on their performance in bone‐related applications. Various synthesis methods and types of 2D nanomaterials, including graphene, graphene oxide, transition metal dichalcogenides, black phosphorus, and MXene are discussed, along with strategies for their incorporation into hydrogel matrices. These composite hydrogels exhibit tunable mechanical properties, high surface area, strong near‐infrared (NIR) photon absorption and controlled release capabilities, making them suitable for a range of regeneration and therapeutic applications. In cancer therapy, 2D‐material‐based hydrogels show promise for photothermal and photodynamic therapies, and drug delivery (chemotherapy). The photothermal properties of these materials enable selective tumor ablation upon NIR irradiation, while their high drug‐loading capacity facilitates targeted and controlled release of chemotherapeutic agents. Additionally, 2D‐materials ‐infused hydrogels exhibit potent antibacterial activity, making them effective against multidrug‐resistant infections and disruption of biofilm generated on implant surface. Moreover, their synergistic therapy approach combines multiple treatment modalities such as photothermal, chemo, and immunotherapy to enhance therapeutic outcomes. In bio‐imaging, these materials serve as versatile contrast agents and imaging probes, enabling their real‐time monitoring during tumor imaging. Furthermore, in bone regeneration, most 2D‐materials incorporated hydrogels promote osteogenesis and tissue regeneration, offering potential solutions for bone defects repair. Overall, the integration of 2D materials into hydrogels presents a promising platform for developing multifunctional theragenerative biomaterials. 

Emerging 2D Nanomaterials‐Integrated Hydrogels: Advancements in Designing Theragenerative Materials for Bone Regeneration and Disease Therapy

Rapid mineralization of graphene-based 3D porous scaffolds by semi-dry electrodeposition for photothermal treatment of tumor-induced bone defects.

Linoleic acid (LA) is a primary n-6 polyunsaturated fatty acid (PUFA), which is of interest to nutritional professionals as it has been associated with health outcomes. However, as some LA-rich foods offer protection against chronic diseases such as CVD (e.g., fatty fish), while others increase risk (e.g., red meat), the individual foods contributing to LA intake may be an important factor to consider. Therefore, this analysis sought to examine whether there are racial/ethnic differences in the proportion of overall LA intake accounted for by individual food groups, via a cross-sectional analysis of 3815 adults participating in the National Health and Nutrition Examination Survey (NHANES; 2017–2018 cycle). Separate multivariable linear regressions models specified the proportion of overall LA intake attributable to each of the nine food groups (dairy, eggs, fat, fish, fruits and vegetables, grains, meat, nuts, and sweets) as the outcome, and race/ethnicity as the predictor, with age, gender, and socioeconomic status (SES) as covariates, in order to estimate whether there were mean differences by race/ethnicity in the proportion of overall LA intake attributable to each of these foods seperately. After a Bonferroni correction for multiple testing, eggs, grains, fruits and vegetables, meat, and fish each accounted for a different proportion of overall LA intake according to racial/ethnic grouping (all p < 0.006 after a Bonferroni correction). These findings indicate the food sources of LA in the diet differ by race/ethnicity, and warrant future investigations into whether this plays a role in health disparities.

/pdf/dietary-sources-of-linoleic-acid-la-differ-by-race-ethnicity-1psd8txx.pdf

Dietary Sources of Linoleic Acid (LA) Differ by Race/Ethnicity in Adults Participating in the National Health and Nutrition Examination Survey (NHANES) between 2017–2018

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Rapid mineralization of graphene-based 3D porous scaffolds by semi-dry electrodeposition for photothermal treatment of tumor-induced bone defects.

Dietary Sources of Linoleic Acid (LA) Differ by Race/Ethnicity in Adults Participating in the National Health and Nutrition Examination Survey (NHANES) between 2017–2018