Biomineralization inspired 3D printed bioactive glass nanocomposite scaffolds orchestrate diabetic bone regeneration by remodeling micromilieu

Zeqian Xu; Xuanyu Qi; Minyue Bao; Tian Zhou; Junfeng Shi; Zhiyan Xu; Mingliang Zhou; Aldo R Boccaccini; Kai Zheng; Xinquan Jiang

doi:10.1016/j.bioactmat.2023.01.024

Biomineralization inspired 3D printed bioactive glass nanocomposite scaffolds orchestrate diabetic bone regeneration by remodeling micromilieu

Bioact Mater. 2023 Feb 8:25:239-255. doi: 10.1016/j.bioactmat.2023.01.024. eCollection 2023 Jul.

Authors

Zeqian Xu^{1

2

3

4

5

6}, Xuanyu Qi^{1

2

3

4

5

6}, Minyue Bao^{1

2

3

4

5

6}, Tian Zhou^{4

7}, Junfeng Shi^{1

2

3

4

5

6}, Zhiyan Xu⁸, Mingliang Zhou^{1

2

3

4

5

6}, Aldo R Boccaccini⁸, Kai Zheng^{9

10}, Xinquan Jiang^{1

2

3

4

5

6}

Affiliations

¹ Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
² College of Stomatology, Shanghai Jiao Tong University, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
³ National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
⁴ National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
⁵ Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
⁶ Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
⁷ Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200023, People's Republic of China.
⁸ Institute of Biomaterials, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058, Erlangen, Germany.
⁹ Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, 210029, People's Republic of China.
¹⁰ Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, People's Republic of China.

Abstract

Type II diabetes mellitus (TIIDM) remains a challenging clinical issue for both dentists and orthopedists. By virtue of persistent hyperglycemia and altered host metabolism, the pathologic diabetic micromilieu with chronic inflammation, advanced glycation end products accumulation, and attenuated biomineralization severely impairs bone regeneration efficiency. Aiming to "remodel" the pathologic diabetic micromilieu, we 3D-printed bioscaffolds composed of Sr-containing mesoporous bioactive glass nanoparticles (Sr-MBGNs) and gelatin methacrylate (GelMA). Sr-MBGNs act as a biomineralization precursor embedded in the GelMA-simulated extracellular matrix and release Sr, Ca, and Si ions enhancing osteogenic, angiogenic, and immunomodulatory properties. In addition to angiogenic and anti-inflammatory outcomes, this innovative design reveals that the nanocomposites can modulate extracellular matrix reconstruction and simulate biomineralization by activating lysyl oxidase to form healthy enzymatic crosslinked collagen, promoting cell focal adhesion, modulating osteoblast differentiation, and boosting the release of OCN, the noncollagenous proteins (intrafibrillar mineralization dependent), and thus orchestrating osteogenesis through the Kindlin-2/PTH1R/OCN axis. This 3D-printed bioscaffold provides a multifunctional biomineralization-inspired system that remodels the "barren" diabetic microenvironment and sheds light on the new bone regeneration approaches for TIIDM.

Keywords: 3D printing; Biomineralization; Enzymatic cross-links; Sr-containing mesoporous bioactive glass nanoparticles; Type II Diabetes mellitus.