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新型AMP2涂层电纺复合支架用于口腔内骨再生的评估:一项概念验证研究。

An evaluation of novel AMP2-coated electrospun composite scaffolds for intraoral bone regeneration: a proof-of-concept study.

作者信息

Slavin Blaire V, Wu Shangtao, Sturm Savanah R, Hwang Kevin K, Almada Ricky, Mirsky Nicholas A, Nayak Vasudev Vivekanand, Witek Lukasz, Coelho Paulo G

机构信息

University of Miami Miller School of Medicine, Miami, FL, United States.

Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, United States.

出版信息

Front Bioeng Biotechnol. 2025 Apr 17;13:1443280. doi: 10.3389/fbioe.2025.1443280. eCollection 2025.

Abstract

BACKGROUND

Alveolar ridge preservation by guided bone regeneration (GBR) is a surgical procedure that can be performed prior to implant placement to increase the likelihood of survival. Autogenic, allogenic, or xenogeneic derived bone (particulate graft) are frequently placed in conjunction with a barrier membrane for GBR; however, advancements in tissue engineering have led to the development of promising synthetic alternatives. Fiber-based scaffolds exhibit high surface-to-volume ratio and thereby improve cellular adhesion, reduce the likelihood of dehiscence and poor bone regeneration often associated with poorly immobilized particulate graft. This study aimed to evaluate the performance of a novel electrospun composite scaffold coated in a recombinant variant of human bone morphogenetic protein-2 (OsteoAdapt) relative to a porcine-derived xenograft. Further, it sought to determine if OsteoAdapt would remain within the defect without a membrane in place, as this is not feasible with the particulate xenograft currently used in clinical practice.

METHODS

Four-walled mandibular defects were created in each adult beagle dog (n = 4 defects per dog; n = 4 dogs for a total of 16 defects). Each defect received one of three experimental (test) groups: (i) OsteoAdapt without membrane (OA), (ii) OsteoAdapt with porcine membrane (OA/ZM), (iii) OsteoAdapt mixed with porcine particulate xenograft (Zcore™) with porcine membrane (OA/P/ZM) and compared to a positive control - Zcore™ with porcine membrane (CTRL). After 4-weeks , bone regeneration was assessed through qualitative volumetric reconstruction, qualitative and quantitative histological analyses.

RESULTS

Histomorphometric measurement of bone regeneration (% bone) within the region of interest revealed no significant differences between OA, OA/ZM, or OA/P/ZM in comparison to the CTRL at 4-weeks ( = 0.086, = 0.218, and = 0.806, respectively). Similarly, evaluation of soft tissue presence (% soft tissue) indicated no significant differences between experimental groups OA, OA/ZM, or OA/P/ZM relative to the CTRL ( = 0.341, = 0.679, = 0.982, respectively). However, qualitative analysis of the histological micrographs demonstrated advanced bone healing characterized by an abundance of nucleation sites for regeneration to occur in defects treated with OA relative to the CTRL. Bone overgrowth beyond the limits of defect borders was observed in groups treated OA/ZM and OA/P/ZM. In contrast to the treatment groups, minimal woven bone was visualized in the CTRL group.

CONCLUSION

Compared to defects treated with porcine-derived particulate and barrier membrane (CTRL), defects filled with OA exhibited bone regeneration throughout the defect, with bone overgrowth when covered by a barrier membrane at 4-weeks . This suggests that the novel combination of AMP-2 and a bioceramic/synthetic polymer-based electrospun scaffold is a suitable candidate for GBR procedures, without a barrier membrane to secure its place within a defect.

摘要

背景

通过引导骨再生(GBR)进行牙槽嵴保存是一种可在种植体植入前进行的外科手术,以提高种植体存活的可能性。自体、异体或异种来源的骨(颗粒移植物)经常与屏障膜联合用于GBR;然而,组织工程学的进展已促使有前景的合成替代物的开发。基于纤维的支架具有高的表面积与体积比,从而改善细胞黏附,降低裂开的可能性以及常常与固定不良的颗粒移植物相关的骨再生不良的可能性。本研究旨在评估一种涂覆有重组人骨形态发生蛋白-2变体(OsteoAdapt)的新型电纺复合支架相对于猪源异种移植物的性能。此外,研究试图确定OsteoAdapt在没有屏障膜的情况下是否会保留在缺损内,因为这对于目前临床实践中使用的颗粒异种移植物是不可行的。

方法

在每只成年比格犬中创建四壁下颌骨缺损(每只犬4个缺损;共4只犬,总计16个缺损)。每个缺损接受三个实验组(测试组)之一:(i)无膜的OsteoAdapt(OA),(ii)带猪膜的OsteoAdapt(OA/ZM),(iii)与猪颗粒异种移植物(Zcore™)混合并带猪膜的OsteoAdapt(OA/P/ZM),并与阳性对照组——带猪膜的Zcore™(CTRL)进行比较。4周后,通过定性体积重建、定性和定量组织学分析评估骨再生情况。

结果

在感兴趣区域内对骨再生(骨百分比)的组织形态计量学测量显示,在4周时,与CTRL相比,OA、OA/ZM或OA/P/ZM之间无显著差异(分别为P = 0.086、P = 0.218和P = 0.806)。同样,对软组织存在情况(软组织百分比)的评估表明,实验组OA、OA/ZM或OA/P/ZM与CTRL相比无显著差异(分别为P = 0.341、P = 0.679、P = 0.982)。然而,组织学显微照片的定性分析表明,与CTRL相比,用OA治疗的缺损中出现了以大量再生成核位点为特征的高级骨愈合。在接受OA/ZM和OA/P/ZM治疗的组中观察到骨生长超出缺损边界。与治疗组相比,CTRL组中可见的编织骨最少。

结论

与用猪源颗粒和屏障膜治疗的缺损(CTRL)相比,填充有OA的缺损在整个缺损处均表现出骨再生,在4周时当被屏障膜覆盖时会有骨过度生长。这表明AMP-2与生物陶瓷/合成聚合物基电纺支架的新型组合是GBR手术的合适候选物,无需屏障膜来将其固定在缺损内。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fda6/12043485/c76b0c1f452a/fbioe-13-1443280-g001.jpg

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