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用于骨再生的3D打印支架上的生物活性涂层:在绵羊股骨髁缺损模型中使用锂皂石递送骨形态发生蛋白-2

Bioactive coatings on 3D printed scaffolds for bone regeneration: Use of Laponite® to deliver BMP-2 in an ovine femoral condyle defect model.

作者信息

Marshall Karen M, McLaren Jane S, Wojciechowski Jonathan P, Callens Sebastien J P, Echalier Cécile, Kanczler Janos M, Rose Felicity R A J, Stevens Molly M, Dawson Jonathan I, Oreffo Richard O C

机构信息

Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD, UK.

School of Pharmacy, Faculty of Science, University of Nottingham, Nottingham NG7 2RD, UK.

出版信息

Biomater Adv. 2024 Nov;164:213959. doi: 10.1016/j.bioadv.2024.213959. Epub 2024 Jul 18.

Abstract

Biomaterial-based approaches for bone regeneration seek to explore alternative strategies to repair non-healing fractures and critical-sized bone defects. Fracture non-union occurs due to a number of factors resulting in the formation of bone defects. Rigorous evaluation of the biomaterials in relevant models and assessment of their potential to translate towards clinical use is vital. Large animal experimentation can be used to model fracture non-union while scaling-up materials for clinical use. Growth factors modulate cell phenotype, behaviour and initiate signalling pathways leading to changes in matrix deposition and tissue formation. Bone morphogenetic protein-2 (BMP-2) is a potent osteogenic growth factor, with a rapid clearance time in vivo necessitating clinical use at a high dose, with potential deleterious side-effects. The current studies have examined the potential for Laponite® nanoclay coated poly(caprolactone) trimethacrylate (PCL-TMA900) scaffolds to bind BMP-2 for enhanced osteoinduction in a large animal critical-sized bone defect. An ovine femoral condyle defect model confirmed PCL-TMA900 scaffolds coated with Laponite®/BMP-2 produced significant bone formation compared to the uncoated PCL-TMA 900 scaffold in vivo, assessed by micro-computed tomography (μCT) and histology. This indicated the ability of Laponite® to deliver the bioactive BMP-2 on the PCL-TMA900 scaffold. Bone formed around the Laponite®/BMP-2 coated PCL-TMA900 scaffold, with no erroneous bone formation observed away from the scaffold material confirming localisation of BMP-2 delivery. The current studies demonstrate the ability of a nanoclay to localise and deliver bioactive BMP-2 within a tailored octet-truss scaffold for efficacious bone defect repair in a large animal model with significant implications for translation to the clinic.

摘要

基于生物材料的骨再生方法旨在探索修复不愈合骨折和临界尺寸骨缺损的替代策略。骨折不愈合是由多种因素导致骨缺损形成所致。在相关模型中对生物材料进行严格评估并评估其转化为临床应用的潜力至关重要。大型动物实验可用于模拟骨折不愈合,同时扩大材料用于临床应用。生长因子调节细胞表型、行为并启动信号通路,导致基质沉积和组织形成发生变化。骨形态发生蛋白-2(BMP-2)是一种强效成骨生长因子,其在体内清除时间快,需要高剂量临床使用,存在潜在有害副作用。目前的研究考察了锂皂石纳米粘土涂层聚(甲基丙烯酸三己酯)(PCL-TMA900)支架结合BMP-2以增强大型动物临界尺寸骨缺损骨诱导的潜力。绵羊股骨髁缺损模型证实,与未涂层的PCL-TMA 900支架相比,涂有锂皂石/BMP-2的PCL-TMA900支架在体内产生了显著的骨形成,通过微型计算机断层扫描(μCT)和组织学评估。这表明锂皂石能够在PCL-TMA900支架上递送生物活性BMP-2。在涂有锂皂石/BMP-2的PCL-TMA900支架周围形成了骨,在远离支架材料处未观察到错误的骨形成,证实了BMP-2递送的定位。目前的研究证明了纳米粘土能够在定制的八面体桁架支架内定位并递送生物活性BMP-2,以在大型动物模型中有效修复骨缺损,这对转化到临床具有重要意义。

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