In situ mineralized PLGA/zwitterionic hydrogel composite scaffold enables high-efficiency rhBMP-2 release for critical-sized bone healing

Peiming Liu; Tianyi Bao; Lian Sun; Zeyi Wang; Jin Sun; Wan Peng; Donglin Gan; Guoyong Yin; Pingsheng Liu; Wei-Bing Zhang; Jian Shen

doi:10.1039/D1BM01521D

In situ mineralized PLGA/zwitterionic hydrogel composite scaffold enables high-efficiency rhBMP-2 release for critical-sized bone healing†

Peiming Liu,

‡^ab Tianyi Bao,‡^c Lian Sun,‡^c Zeyi Wang,^a Jin Sun,^a Wan Peng,^a Donglin Gan,^a Guoyong Yin,^c Pingsheng Liu,

*^a Wei-Bing Zhang*^cd and Jian Shen*^ae

Author affiliations

* Corresponding authors

^a Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Bio-Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, P. R. China
E-mail: liups@njnu.edu.cn

^b Changzhou Institute of Materia Medica Co., Ltd., Changzhou, Jiangsu 213000, China

^c Department of Orthopedics, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, P. R. China

^d Department of Stomatology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, China
E-mail: wbzhang@suda.edu.cn

^e Jiangsu Engineering Research Center of Interfacial Chemistry, Nanjing University, Nanjing 210093, P. R. China
E-mail: shenjian@nju.edu.cn

Abstract

Osteoconductive and osteoinductive scaffolds are highly desirable for functional restoration of large bone defects. Here, we report an in situ mineralized poly(lactic-co-glycolic acid)/poly[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide hydrogel (PLGA/PSBMA) scaffold as a novel high-efficiency carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2) for bone tissue regeneration. By virtue of the oppositely charged structure, the zwitterionic PSBMA component is able to template well-integrated dense mineralization of calcium phosphate throughout the PLGA/PSBMA scaffold. The high affinity between rhBMP-2 and the mineralized matrix, combined with the capability of the zwitterionic hydrogel to sequester and to enable sustained release of ionic proteins, endows the mineralized PLGA/PSBMA scaffolds with high-efficiency sustained release of rhBMP-2 (only 1.7% release within 35 days), thus enabling robust healing of critical-sized (5 mm) nonunion calvarial defects in rats at an ultralow dosage of rhBMP-2 (150 ng per scaffold), at which level successful healing of critical-sized bone defects has never been reported. These findings show that the mineralized PLGA/PSBMA scaffold is promising for bone defect repair.

Biomaterials Science

In situ mineralized PLGA/zwitterionic hydrogel composite scaffold enables high-efficiency rhBMP-2 release for critical-sized bone healing†

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In situ mineralized PLGA/zwitterionic hydrogel composite scaffold enables high-efficiency rhBMP-2 release for critical-sized bone healing

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