An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration.

IF 6.4 1区 医学 Q1 CELL & TISSUE ENGINEERING npj Regenerative Medicine Pub Date : 2023-09-29 DOI:10.1038/s41536-023-00330-2
Juan Antonio Romero-Torrecilla, José María Lamo-Espinosa, Purificación Ripalda-Cemboráin, Tania López-Martínez, Gloria Abizanda, Luis Riera-Álvarez, Sergio Ruiz de Galarreta-Moriones, Asier López-Barberena, Naiara Rodríguez-Flórez, Reyes Elizalde, Vineetha Jayawarna, José Valdés-Fernández, Miguel Echanove-González de Anleo, Peter Childs, Elena de Juan-Pardo, Manuel Salmeron-Sanchez, Felipe Prósper, Emma Muiños-López, Froilán Granero-Moltó
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Abstract

During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 μg/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses.

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一种在骨再生过程中有效递送rhBMP-2和间充质祖细胞的工程骨膜。
在骨再生过程中,骨膜充当关键再生线索的载体,将骨软骨前生殖细胞和关键生长因子输送到受伤的骨中。我们开发了一种生物相容性的3D聚己内酯(PCL)熔融电写膜,用作模拟骨膜。PCL膜的聚(丙烯酸乙酯)涂层允许通过纤连蛋白和低剂量重组人BMP-2(rhBMP-2)(10-25μg/ml)介导的功能化,从而在体外产生有效、持续的骨诱导。在体内,rhBMP-2功能化的模拟骨膜在治疗大鼠临界尺寸股骨缺损方面表现出再生潜力,具有高效的愈合和功能恢复(80%-93%)。通过移植骨膜衍生的间充质细胞迁移到骨缺损及其存活,模拟骨膜也被证明对细胞递送是有效的。最终,模拟骨膜证明了其将关键干细胞和形态发生素输送到损伤部位的能力,当与前所未有的低剂量rhBMP-2结合时,在体内暴露出治疗和翻译潜力。
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来源期刊
npj Regenerative Medicine
npj Regenerative Medicine Engineering-Biomedical Engineering
CiteScore
10.00
自引率
1.40%
发文量
71
审稿时长
12 weeks
期刊介绍: Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.
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