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Biodegradable Zwitterion/PLGA Scaffold Enables Robust Healing of Rat Calvarial Defects with Ultralow Dose of rhBMP-2.
Biomacromolecules ( IF 5.5 ) Pub Date : 2020-06-04 , DOI: 10.1021/acs.biomac.0c00540
Peiming Liu 1 , Lian Sun 2 , Zeyi Wang 1 , Jin Sun 1 , Yaning Dong 1 , Lin Cao 1 , Jian Shen 1, 3 , Wei-Bing Zhang 2 , Pingsheng Liu 1
Affiliation  

Designing smart scaffolds to reduce administration dosage under the premise of functional healing of bone defects to avoid the severe side effects associated with BMP-2 treatments is one of the essential goals in bone tissue engineering. Here, we report a novel biodegradable PLGA/PSBMA composite as the scaffold for bone tissue engineering. The introduction of zwitterionic PSBMA components can alter the intrinsic burst degradation behavior of PLGA and enable a sustained degradation of the scaffold over the time. The PLGA/PSBMA scaffold can sequester rhBMP-2 and enable a sustained release of the sequestered rhBMP-2 with preserved bioactivity. Furthermore, PLGA/PSBMA scaffolds were able to guide robust healing of critical-sized nonunion calvarial defects (5 mm) at an ultralow dose of 400 ng/scaffold, at which level successful healing of critical-sized bone defects has never been reported. These findings indicate the PLGA/PSBMA scaffolds as novel high-efficiency rhBMP-2 delivery vehicles for bone tissue engineering, and the concept of utilizing the material, which is capable of maintaining the bioactivity of the proteins in the preparation of scaffolds, may open a new avenue for the design of smart scaffolds/vehicles for high-efficiency protein/bioactive drug therapies.

中文翻译:

可生物降解的两性离子/ PLGA支架能够以超低剂量的rhBMP-2强大地治愈大鼠颅骨缺损。

在骨缺损的功能性愈合的前提下设计智能支架以减少给药剂量,以避免与BMP-2治疗相关的严重副作用,这是骨组织工程学的基本目标之一。在这里,我们报告了一种新型的可生物降解的PLGA / PSBMA复合材料,作为骨组织工程的支架。两性离子PSBMA组分的引入可以改变PLGA固有的爆裂降解行为,并能使支架随时间持续降解。PLGA / PSBMA支架可以螯合rhBMP-2,并能够持续释放螯合的rhBMP-2,同时保留生物活性。此外,PLGA / PSBMA支架能够以400 ng /支架的超低剂量指导关键尺寸的不愈合颅骨缺损(5毫米)的稳固愈合,从未报道过成功治愈关键尺寸骨缺损的水平。这些发现表明,PLGA / PSBMA支架是用于骨组织工程的新型高效rhBMP-2传递载体,利用这种能够在支架制备过程中保持蛋白质生物活性的材料的概念可能会打开为高效蛋白质/生物活性药物治疗设计智能支架/车辆的新途径。
更新日期:2020-07-13
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