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Sequential SDF-1/CGRP-releasing smart composite hydrogel promotes osteoporotic fracture healing by targeting sensory nerve-regulated bone remodeling

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机构: [1]Soochow Univ, Affiliated Hosp 2, Dept Orthoped, Sanxiang Rd 1055, Suzhou 215004, Peoples R China [2]Shanghai Jiao Tong Univ, TongRen Hosp, Dept Orthoped, Sch Med, Xianxia Rd 1111, Shanghai 200336, Peoples R China [3]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Orthoped, Shanghai 200235, Peoples R China [4]Tongji Univ, Tongji Hosp, Dept Pathol, Shanghai 200065, Peoples R China [5]Shanghai Jiao Tong Univ, Tongren Hosp, Lab Key Technol & Mat Minimally Invas Spine Surg, Sch Med, Shanghai 200336, Peoples R China [6]Shanghai Jiao Tong Univ, Ctr Spinal Minimally Invas Res, Shanghai 200336, Peoples R China
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关键词: Osteoporotic fractures Smart hydrogel Sensory nerves Callus remodeling Fracture healing

摘要:
Osteoporotic fractures typically exhibit delayed healing due to impaired cell recruitment, chronic inflammation, and disrupted neurovascular signaling. Sensory nerve signaling plays a crucial role in fracture repair, and its deficiency is a significant factor leading to delayed healing. Addressing these deficiencies is crucial to overcoming the challenges associated with delayed bone repair in osteoporosis. In this study, a smart composite hydrogel (denoted as OCS-MPC) was synthesized by embedding CGRP-functionalized polydopamine-coated MXene nanosheets (MXene/PDA/CGRP) into boronic acid-modified oxidized hyaluronic acid-crosslinked carboxymethyl chitosan (OHA-PBA/CMCS) hydrogel loaded with SDF-1. OCS-MPC hydrogel enables the controlled release of SDF-1 and CGRP, aiming to promote early callus formation and late-stage callus remodeling in osteoporotic fractures. Due to dynamic crosslinking via imine and borate ester bonds, OCS-MPC exhibits rapid gelation, injectability, and self-healing properties. In vitro experiments demonstrated excellent osteogenic, angiogenic, and neurogenic properties of OCS-MPC hydrogel. In vivo studies using an osteoporotic femoral fracture model showed that OCS-MPC hydrogel enhanced MSCs recruitment via the SDF-1/CXCR4 signaling axis, significantly improving callus formation in the early stages of fracture repair. Additionally, OCS-MPC hydrogel significantly promoted callus mineralization and remodeling in the later stages of osteoporotic fracture healing through enhancing CGRP signaling. Immunofluorescence analysis further confirmed increased expression of TUBB3, CGRP, and CD31, indicating successful regeneration of the neurovascular network. These findings highlight the potential of OCS-MPC hydrogel in addressing both early and late-stage challenges of osteoporotic fracture healing, providing a promising therapeutic strategy for enhancing bone regeneration in osteoporotic patients.

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出版当年[2025]版:
大类 | 1 区 医学
小类 | 1 区 材料科学:生物材料 2 区 工程:生物医学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 材料科学:生物材料 2 区 工程:生物医学
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出版当年[2023]版:
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS
最新[2023]版:
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子: 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

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第一作者机构: [1]Soochow Univ, Affiliated Hosp 2, Dept Orthoped, Sanxiang Rd 1055, Suzhou 215004, Peoples R China [2]Shanghai Jiao Tong Univ, TongRen Hosp, Dept Orthoped, Sch Med, Xianxia Rd 1111, Shanghai 200336, Peoples R China
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通讯机构: [2]Shanghai Jiao Tong Univ, TongRen Hosp, Dept Orthoped, Sch Med, Xianxia Rd 1111, Shanghai 200336, Peoples R China [5]Shanghai Jiao Tong Univ, Tongren Hosp, Lab Key Technol & Mat Minimally Invas Spine Surg, Sch Med, Shanghai 200336, Peoples R China [6]Shanghai Jiao Tong Univ, Ctr Spinal Minimally Invas Res, Shanghai 200336, Peoples R China
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