Industrial Electrospinning Machine| Micromotion-Driven "Mechanical-Electrical-PharmaceuticalCoupling" Bone-Guiding Membrane Modulates Stress.ConcentratingInflammation Under Diabetic Fractures
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Author: Nanofiberlabs
Publish Time: 2025-06-09
Origin: Mechanical-Electrical-Pharmaceutical Coupling System
Zhang Hao/Xiaochen Zhang (Advanced Materials): Micromotion-Driven "Mechanical-Electrical-Pharmaceutical Coupling" Bone-Guiding Membrane Modulates Stress-Concentrating Inflammation in Diabetic Fractures
The use of piezoelectric materials to convert micromechanical energy at fracture sites into electrical signals for modulating stress-concentrated inflammation has emerged as a promising strategy for treating diabetic fractures. However, traditional bone-guiding membranes face challenges in diabetic fracture repair due to their passive and imprecise drug release profiles.
Recently, Hao Zhang and colleagues from the First Affiliated Hospital of Naval Medical University developed a breakthrough "mechanical-electrical-pharmaceutical coupling" bone-guiding membrane (Met-PF@PPy), providing an innovative solution for active regulation in diabetic fracture healing. Junhao Sui, an attending physician at the First Affiliated Hospital, is the first author, with Professors Shuogui Xu and Hao Zhang, and Xiaochen Zhang from Shanghai Ninth People's Hospital, serving as corresponding authors.The team constructed the Met-PF@PPy system, which converts mechanical energy from fracture micromotion into electrical signals to reconstruct the disrupted electrical microenvironment at the fracture site. This transforms the adverse factor of excessive micromotion in diabetic patients into a healing-promoting electrical microenvironment, powered solely by natural fracture micromotion without external energy sources. The generated electrical signals inhibit inflammation via M1-to-M2 macrophage polarization and enhance osteogenesis. Meanwhile, metformin (Met) suppresses the NF-κB pathway to reduce pro-inflammatory cytokines and activates the AMPK pathway to promote osteogenesis and angiogenesis.
The study was published in Advanced Materials under the title "Micromotion-Driven 'Mechanical-Electrical-Pharmaceutical Coupling' Bone-Guiding Membrane Modulates Stress-Concentrating Inflammation Under Diabetic Fractures."
Construction and Validation Experiments of Met-PF@PPy:
A piezoelectric PVDF bone-guiding membrane was fabricated via electrospinning to mimic the unique micromechanical environment of diabetic fracture sites. Metformin (Met) was incorporated into a polypyrrole (PPy) coating through in-situ oxidative polymerization, creating a micromotion-driven "mechanical-electrical-pharmaceutical" coupled membrane (Figure 1a). In vitro cell assays investigated the effects of electrical signals on osteogenic differentiation of stem cells and macrophage polarization, while a diabetic mouse femoral fracture model validated the efficacy of electrical stimulation and drug release in promoting healing. This strategy leverages PVDF's piezoelectric properties to convert mechanical energy into electrical signals, triggering electrochemical reduction of PPy for precise drug release. By integrating inflammation modulation and bone repair, this innovation addresses multifaceted challenges in diabetic fracture healing and advances piezoelectric materials in regenerative medicine.
Figure 1: Schematic of Met-PF@PPy preparation via electrospinning and its application in diabetic fracture repair in mice. (a) Fabrication process; (b) Repair mechanism.
Synthesis and Characterization of Met-PF@PPy:
The piezoelectric PVDF membrane was prepared via electrospinning, with Met doped into the PPy coating through in-situ polymerization to form Met-PF@PPy, which exhibits excellent piezoelectricity and biocompatibility. The membrane's conductivity, stability, hydrophilicity, and controllability enable conversion of mechanical energy to electrical energy, promoting bone healing, angiogenesis, and anti-inflammation. Synthesis and characterization results are shown in Figure 2.
Figure 2: Synthesis and characterization of Met-PF@PPy.
Anti-Inflammatory Performance of Met-PF@PPy:
In vitro experiments demonstrated that Met-PF@PPy promotes macrophage polarization toward the anti-inflammatory M2 phenotype, evidenced by downregulation of CD86 and upregulation of CD206—critical for tissue healing in diabetic conditions. Sequencing analysis revealed significant suppression of M1-associated inflammatory pathways (MAPK, Toll-like receptor, NF-κB). Met-PF@PPy reduces M1 macrophage activation and ROS production without impairing macrophage recruitment, acting as an immunomodulatory biomaterial that regulates polarization rather than depletes macrophages (Figure 3).
Figure 3: In vitro evaluation of anti-inflammatory performance of Met-PF@PPy.
Osteogenic Performance of Met-PF@PPy:
Osteogenic differentiation of rBMSCs was evaluated via ALP activity, calcium deposition, and gene expression (ALP, RUNX2, BMP2, OPN, OCN, COL1). The Met-PF@PPy group showed significantly higher ALP activity and uniform calcium deposition, indicating a favorable immune microenvironment for osteogenesis. Upregulated osteogenic gene expression further confirmed its superior osteoinductive properties (Figure 4).
Figure 4: In vitro evaluation of osteogenic performance of Met-PF@PPy.
Conclusion and Outlook:
This study introduces the "mechanical-electrical-pharmaceutical coupling" system via the Met-PF@PPy nanomembrane, which converts continuous fracture micromotion into local electrical signals and enables precise Met release to dynamically regulate inflammation and osteogenesis. The findings highlight the importance of integrating biomechanical stimulation, electrical signaling, and targeted drug delivery in fracture repair under inflammatory conditions. Insights from micromotion research underscore the role of controlled mechanical forces in optimizing healing, particularly for small-gap fractures. Future research may focus on material design optimization and applications in other clinical scenarios, paving the way for personalized bone repair therapies.
