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一种可注射的丝基水凝胶作为用于临界尺寸骨缺损再生的新型生物矿化种子床。

An Injectable silk-based hydrogel as a novel biomineralization seedbed for critical-sized bone defect regeneration.

作者信息

Zhu Yuhui, Gu Hao, Yang Jiawei, Li Anshuo, Hou Lingli, Zhou Mingliang, Jiang Xinquan

机构信息

Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China.

College of Stomatology, Shanghai Jiao Tong University, No. 115 Jinzun Road, Shanghai, 200125, China.

出版信息

Bioact Mater. 2024 Feb 8;35:274-290. doi: 10.1016/j.bioactmat.2024.01.024. eCollection 2024 May.


DOI:10.1016/j.bioactmat.2024.01.024
PMID:38370865
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10873665/
Abstract

The healing process of critical-sized bone defects urges for a suitable biomineralization environment. However, the unsatisfying repair outcome usually results from a disturbed intricate milieu and the lack of in situ mineralization resources. In this work, we have developed a composite hydrogel that mimics the natural bone healing processes and serves as a seedbed for bone regeneration. The oxidized silk fibroin and fibrin are incorporated as rigid geogrids, and amorphous calcium phosphate (ACP) and platelet-rich plasma serve as the fertilizers and loam, respectively. Encouragingly, the seedbed hydrogel demonstrates excellent mechanical and biomineralization properties as a stable scaffold and promotes vascularized bone regeneration in vivo. Additionally, the seedbed serves a succinate-like function via the PI3K-Akt signaling pathway and subsequently orchestrates the mitochondrial calcium uptake, further converting the exogenous ACP into endogenous ACP. Additionally, the seedbed hydrogel realizes the succession of calcium resources and promotes the evolution of the biotemplate from fibrin to collagen. Therefore, our work has established a novel silk-based hydrogel that functions as an in-situ biomineralization seedbed, providing a new insight for critical-sized bone defect regeneration.

摘要

临界尺寸骨缺损的愈合过程迫切需要一个合适的生物矿化环境。然而,令人不满意的修复结果通常是由于复杂的微环境紊乱以及缺乏原位矿化资源所致。在这项工作中,我们开发了一种复合水凝胶,它模仿天然骨愈合过程,并作为骨再生的苗床。氧化丝素蛋白和纤维蛋白作为刚性格栅掺入,无定形磷酸钙(ACP)和富血小板血浆分别作为肥料和壤土。令人鼓舞的是,作为一种稳定的支架,苗床水凝胶表现出优异的力学和生物矿化性能,并在体内促进血管化骨再生。此外,苗床通过PI3K-Akt信号通路发挥类似琥珀酸的功能,随后协调线粒体钙摄取,进一步将外源性ACP转化为内源性ACP。此外,苗床水凝胶实现了钙资源的连续供应,并促进了生物模板从纤维蛋白到胶原蛋白的演变。因此,我们的工作建立了一种新型的基于丝的水凝胶,它作为原位生物矿化苗床发挥作用,为临界尺寸骨缺损再生提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/6fc5f8a5fd95/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/ffe08e7b7eeb/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/a5398b694b29/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/b6891c86f15f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/f40c348f3558/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/7d959cef7ab4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/c2c63dc9f69d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/5da4030484a3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/444975246e36/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/6fc5f8a5fd95/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/ffe08e7b7eeb/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/a5398b694b29/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/b6891c86f15f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/f40c348f3558/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/7d959cef7ab4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/c2c63dc9f69d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/5da4030484a3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/444975246e36/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/10873665/6fc5f8a5fd95/gr7.jpg

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本文引用的文献

[1]
Mineralization of Bone Extracellular Matrix-like Scaffolds Fabricated as Silk Sericin-Functionalized Dense Collagen-Fibrin Hybrid Hydrogels.

Pharmaceutics. 2023-3-28

[2]
Bio-Inspired Multiscale Design for Strong and Tough Biological Ionogels.

Adv Sci (Weinh). 2023-5

[3]
Biomimetic Mineralization of Bone-Like Hydroxyapatite in Hydrogel for the Acceleration of Bone Regeneration.

ACS Appl Mater Interfaces. 2023-1-11

[4]
Role of sodium dependent SLC13 transporter inhibitors in various metabolic disorders.

Mol Cell Biochem. 2023-8

[5]
Self-Adhesive Hydrogel Biomimetic Periosteum to Promote Critical-Size Bone Defect Repair via Synergistic Osteogenesis and Angiogenesis.

ACS Appl Mater Interfaces. 2022-8-17

[6]
Fracture hematoma micro-architecture influences transcriptional profile and plays a crucial role in determining bone healing outcomes.

Biomater Adv. 2022-8

[7]
Orchestration of energy metabolism and osteogenesis by Mg facilitates low-dose BMP-2-driven regeneration.

Bioact Mater. 2022-3-24

[8]
Bioactive Silk Fibroin-Based Hybrid Biomaterials for Musculoskeletal Engineering: Recent Progress and Perspectives.

ACS Appl Bio Mater. 2021-9-20

[9]
Multifunctional Nanomachinery for Enhancement of Bone Healing.

Adv Mater. 2022-3

[10]
Amorphous calcium phosphate nanoparticles using adenosine triphosphate as an organic phosphorus source for promoting tendon-bone healing.

J Nanobiotechnology. 2021-9-8

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