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Programmable DNA-Peptide Conjugated Hydrogel via Click Chemistry for Sequential Modulation of Peripheral Nerve Regeneration

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机构: [1]Shanghai Jiao Tong Univ, Tongren Hosp, Hongqiao Int Inst Med, Ctr Spinal Minimally Invas Res,Lab Key Technol & M, Shanghai 200336, Peoples R China [2]Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Dept Rehabil Med, Shanghai 200336, Peoples R China [3]Fudan Univ, Eye & ENT Hosp, Eye Inst, Shanghai 200031, Peoples R China [4]Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200031, Peoples R China [5]Fudan Univ, Chinese Acad Med Sci, NHC Key Lab Myopia, Key Lab Myopia, Shanghai 200031, Peoples R China [6]Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Traumatol & Orthopaed, Dept Orthopaed,Shanghai Key Lab Prevent & Treatme, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China
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关键词: click chemistry DNA hydrogel peripheral nerve regeneration regenerative medicine tissue engineering

摘要:
During peripheral nerve regeneration, current deoxyribonucleic acid (DNA)-based therapeutic platforms face the challenge of precisely regulating Schwann cells (SCs) fate to sustain their repair phenotype due to their inability to stably and precisely integrate multiple bioactive components. Herein, the strain-promoted azide-alkyne cycloaddition reaction is utilized to integrate the neurotrophic factor mimetic peptide RGI and the laminin-derived peptide IKVAV into DNA monomers. Through DNA sequence self-assembly, a programmable DNA-peptide conjugated hydrogel is constructed for loading bone marrow mesenchymal stem cell-derived exosomes. This programmable hydrogel can rapidly, stably, and precisely integrate various bioactive components into the hydrogel network, thereby enabling sequential modulation of peripheral nerve repair. In vitro, studies show that this hydrogel, through sequential modulation mechanisms, can activate the neuregulin-1 (Nrg1)/ErbB pathway to induce the reprogramming of SCs and promote the recruitment and proliferation of repair SCs. The induced repair SCs promote neuronal axon outgrowth and enhance tube formation in endothelial cells. In vivo, this programmable hydrogel can gelate in situ through intraneural injection in a rat sciatic nerve crush injury model, promoting nerve regeneration and functional recovery. In summary, this work provides an effective and practical strategy for peripheral nerve regeneration.

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出版当年[2025]版:
大类 | 1 区 材料科学
小类 | 1 区 化学:综合 1 区 材料科学:综合 1 区 纳米科技 1 区 物理:应用 1 区 物理:凝聚态物理
最新[2025]版:
大类 | 1 区 材料科学
小类 | 1 区 化学:综合 1 区 材料科学:综合 1 区 纳米科技 1 区 物理:应用 1 区 物理:凝聚态物理
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出版当年[2023]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 CHEMISTRY, PHYSICAL Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY Q1 PHYSICS, APPLIED Q1 PHYSICS, CONDENSED MATTER
最新[2023]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 CHEMISTRY, PHYSICAL Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY Q1 PHYSICS, APPLIED Q1 PHYSICS, CONDENSED MATTER

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第一作者机构: [1]Shanghai Jiao Tong Univ, Tongren Hosp, Hongqiao Int Inst Med, Ctr Spinal Minimally Invas Res,Lab Key Technol & M, Shanghai 200336, Peoples R China
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通讯机构: [3]Fudan Univ, Eye & ENT Hosp, Eye Inst, Shanghai 200031, Peoples R China [4]Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200031, Peoples R China [5]Fudan Univ, Chinese Acad Med Sci, NHC Key Lab Myopia, Key Lab Myopia, Shanghai 200031, Peoples R China
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