Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model

Fang, Chih-Hsiang; Sun, Chung-Kai; Lin, Yi-Wen; Hung, Min-Chih; Lin, Hung-Ying; Li, Ching-Hung; Lin, I-Ping; Chang, Hung-Chen; Sun, Jui-Sheng; Chang, Jenny Zwei-Chieng

doi:10.3390/ijms23010558

Open AccessArticle

Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model

by

Chih-Hsiang Fang

^1,†

,

Chung-Kai Sun

^2,†,

Yi-Wen Lin

^3,4,

Min-Chih Hung

⁵,

Hung-Ying Lin

⁵,

Ching-Hung Li

^5,6,

I-Ping Lin

⁷,

Hung-Chen Chang

⁸,

Jui-Sheng Sun

^{1,9,10,11,*,‡}

and

Jenny Zwei-Chieng Chang

^5,6,*,‡

¹

Trauma and Emergency Center, China Medical University Hospital, No. 2, Xueshi Rd., North Dist., Taichung City 40447, Taiwan

²

Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan

³

Institute of Biomedical Engineering, College of Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan

⁴

Institute of Biomedical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan

⁵

Department of Dentistry, National Taiwan University Hospital, No. 1, Chang-Te Street, Taipei 10048, Taiwan

⁶

School of Dentistry, College of Medicine, National Taiwan University, No. 1, Chang-Te Street, Taipei 10048, Taiwan

⁷

Department of Dentistry, National Taiwan University Hospital, Hisnchu Branch, No. 25, Lane 442, Sec. 1, Jingguo Rd., Hsinchu City 30059, Taiwan

⁸

Gin Chen Dental Clinic, No. 31, Long Chiang Rd., Taipei 10606, Taiwan

⁹

College of Medicine, China Medical University, YingCai Campus, No. 91, Xueshi Rd., North Dist., Taichung City 40402, Taiwan

¹⁰

College of Biomedical Engineering, China Medical University, YingCai Campus, No. 91, Xueshi Rd., North Dist., Taichung City 40402, Taiwan

¹¹

Department of Orthopedic Surgery, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan

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^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors contributed equally to this work.

Int. J. Mol. Sci. 2022, 23(1), 558; https://doi.org/10.3390/ijms23010558

Submission received: 23 November 2021 / Revised: 21 December 2021 / Accepted: 22 December 2021 / Published: 5 January 2022

(This article belongs to the Special Issue Bone Development and Regeneration 2.0)

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Abstract

In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen^® groups in a critical size rat alveolar bone defect model. GHMS was synthesized by co-precipitating calcium hydroxide and orthophosphoric acid within gelatin solution, incorporating metformin, and cross-linked by microbial transglutaminase. The morphology, characterization, and biocompatibility of scaffold were examined. The in vitro effects of GHMS on osteogenic gene and protein expressions were evaluated. In vivo bone formation was assessed in a critical size rat alveolar bone defect model with micro-computed tomography and histological examination by comparing GHMS with extraction-only, Sinbone, and Bio-Oss Collagen^®. The synthesized GHMS had a highly interconnected porous structure with a mean pore size of 81.85 ± 13.8 µm. GHMS exhibited good biocompatibility; promoted ALPL, RUNX2, SP7, BGLAP, SPARC and Col1a1 gene expressions; and upregulated the synthesis of osteogenic proteins, including osteonectin, osteocalcin, and collagen type I. In critical size rat alveolar bone defects, GHMS showed superior bone regeneration compared to extraction-only, Sinbone, and Bio-Oss Collagen^® groups as manifested by greater alveolar ridge preservation, while more bone formation with a lower percentage of connective tissue and residual scaffold at the defect sites grafted with GHMS in histological staining. The GHMS presented in this study may be used as a potential bone substitute to regenerate alveolar bone. The good biocompatibility, relatively fast degradation, interconnected pores allowing vascularization, and higher bioactivity properties of the components of the GHMS (gelatin, nHA, and metformin) may contribute to direct osteogenesis.

Keywords: metformin; nanocomposite; critical size defect; alveolar ridge preservation; bone regeneration

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MDPI and ACS Style

Fang, C.-H.; Sun, C.-K.; Lin, Y.-W.; Hung, M.-C.; Lin, H.-Y.; Li, C.-H.; Lin, I.-P.; Chang, H.-C.; Sun, J.-S.; Chang, J.Z.-C. Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model. Int. J. Mol. Sci. 2022, 23, 558. https://doi.org/10.3390/ijms23010558

AMA Style

Fang C-H, Sun C-K, Lin Y-W, Hung M-C, Lin H-Y, Li C-H, Lin I-P, Chang H-C, Sun J-S, Chang JZ-C. Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model. International Journal of Molecular Sciences. 2022; 23(1):558. https://doi.org/10.3390/ijms23010558

Chicago/Turabian Style

Fang, Chih-Hsiang, Chung-Kai Sun, Yi-Wen Lin, Min-Chih Hung, Hung-Ying Lin, Ching-Hung Li, I-Ping Lin, Hung-Chen Chang, Jui-Sheng Sun, and Jenny Zwei-Chieng Chang. 2022. "Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model" International Journal of Molecular Sciences 23, no. 1: 558. https://doi.org/10.3390/ijms23010558

APA Style

Fang, C.-H., Sun, C.-K., Lin, Y.-W., Hung, M.-C., Lin, H.-Y., Li, C.-H., Lin, I.-P., Chang, H.-C., Sun, J.-S., & Chang, J. Z.-C. (2022). Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model. International Journal of Molecular Sciences, 23(1), 558. https://doi.org/10.3390/ijms23010558

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Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model

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