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用于椎间盘修复的3D生物打印软骨生成明胶甲基丙烯酸酯-聚(乙二醇)二丙烯酸酯复合支架

3D Bioprinted Chondrogenic Gelatin Methacrylate-Poly(ethylene glycol) Diacrylate Composite Scaffolds for Intervertebral Disc Restoration.

作者信息

Astudillo Potes Maria D, Tilton Maryam, Mitra Indranath, Liu Xifeng, Dashtdar Babak, Camilleri Emily T, Elder Benjamin D, Lu Lichun

机构信息

Mayo Clinic Alix School of Medicine, Rochester, Minnesota, USA.

Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota, USA.

出版信息

Int J Extrem Manuf. 2025 Feb;7(1). doi: 10.1088/2631-7990/ad878e. Epub 2024 Nov 19.

DOI:10.1088/2631-7990/ad878e
PMID:40861018
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12377657/
Abstract

Degenerative spine pathologies, including intervertebral disc (IVD) degeneration, present a significant healthcare challenge due to their association with chronic pain and disability. This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology, specifically visible light-based digital light processing (VL-DLP), to fabricate tissue scaffolds that closely mimic the native architecture of the IVD. Utilizing a hybrid bioink composed of gelatin methacrylate (GelMA) and poly (ethylene glycol) diacrylate (PEGDA) at a 10% concentration, we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD. Preconditioning rat bone marrow-derived mesenchymal stem cell (rBMSC) spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system. Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses. The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders, highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix.

摘要

退行性脊柱疾病,包括椎间盘(IVD)退变,因其与慢性疼痛和残疾相关,给医疗保健带来了重大挑战。本研究探索了一种利用3D生物打印技术,特别是基于可见光的数字光处理(VL-DLP)来进行IVD再生的创新方法,以制造紧密模仿IVD天然结构的组织支架。使用由10%浓度的甲基丙烯酸明胶(GelMA)和聚(乙二醇)二丙烯酸酯(PEGDA)组成的混合生物墨水,我们实现了更高的打印保真度和适合IVD等承重应用的机械性能。在将大鼠骨髓间充质干细胞(rBMSC)球体掺入GelMA-PEGDA支架之前,先用软骨生成培养基对其进行预处理,进一步提高了该系统的再生能力。我们的研究结果表明,这种生物打印支架不仅支持细胞活力和整合,而且在大鼠尾椎间盘模型中有助于恢复椎间盘高度,且不会引发不良炎症反应。该研究强调了结合先进生物打印技术和细胞预处理策略来开发针对IVD退变和其他肌肉骨骼疾病的有效治疗方法的潜力,突出了进一步研究细胞迁移与水凝胶基质之间动态相互作用的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0149/12377657/8f5fc87ec100/nihms-2034619-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0149/12377657/f3fd1dd39d68/nihms-2034619-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0149/12377657/fae2333544ad/nihms-2034619-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0149/12377657/5008c54eb2d6/nihms-2034619-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0149/12377657/8f5fc87ec100/nihms-2034619-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0149/12377657/f3fd1dd39d68/nihms-2034619-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0149/12377657/fae2333544ad/nihms-2034619-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0149/12377657/5008c54eb2d6/nihms-2034619-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0149/12377657/8f5fc87ec100/nihms-2034619-f0004.jpg

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本文引用的文献

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Mesenchymal Stem Cell Spheroids: A Promising Tool for Vascularized Tissue Regeneration.间质干细胞球:用于血管化组织再生的有前途的工具。
Tissue Eng Regen Med. 2024 Jul;21(5):673-693. doi: 10.1007/s13770-024-00636-2. Epub 2024 Apr 5.
2
Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects.基于水凝胶的椎间盘再生策略:进展、挑战与临床前景
Gels. 2024 Jan 15;10(1):62. doi: 10.3390/gels10010062.
3
Application of 3D- printed hydrogels in wound healing and regenerative medicine.3D打印水凝胶在伤口愈合和再生医学中的应用。
Biomed Pharmacother. 2023 Nov;167:115416. doi: 10.1016/j.biopha.2023.115416. Epub 2023 Sep 6.
4
Visible light-induced 3D bioprinted injectable scaffold for minimally invasive tissue regeneration.可见光诱导的 3D 生物打印可注射支架用于微创组织再生。
Biomater Adv. 2023 Oct;153:213539. doi: 10.1016/j.bioadv.2023.213539. Epub 2023 Jun 30.
5
Potential Role for Stem Cell Regenerative Therapy as a Treatment for Degenerative Disc Disease and Low Back Pain: A Systematic Review.干细胞再生治疗作为退行性椎间盘疾病和下腰痛治疗方法的潜在作用:系统评价。
Int J Mol Sci. 2023 May 17;24(10):8893. doi: 10.3390/ijms24108893.
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Three-Dimensional Spheroid Culture of Human Mesenchymal Stem Cells: Offering Therapeutic Advantages and In Vitro Glimpses of the In Vivo State.人骨髓间充质干细胞的三维球体培养:提供治疗优势和对体内状态的体外观察。
Stem Cells Transl Med. 2023 May 15;12(5):235-244. doi: 10.1093/stcltm/szad011.
7
Tissue-Engineered Injectable Gelatin-Methacryloyl Hydrogel-Based Adjunctive Therapy for Intervertebral Disc Degeneration.基于组织工程可注射甲基丙烯酰化明胶水凝胶的椎间盘退变辅助治疗
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Intervertebral Disc Tissue Engineering Using Additive Manufacturing.基于增材制造的椎间盘组织工程
Gels. 2022 Dec 29;9(1):25. doi: 10.3390/gels9010025.
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