Injectable hydrogel composite containing modified gold nanoparticles: implication in bone tissue regeneration

Abstract

Donghyun Lee,1 Dong Nyoung Heo,2 Ha Ram Nah,3 Sang Jin Lee,1 Wan-Kyu Ko,4 Jae Seo Lee,3 Ho-Jin Moon,1 Jae Beum Bang,5 Yu-Shik Hwang,6 Rui L Reis,1,7 Il Keun Kwon1 1Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea; 2Department of Engineering Science and Mechanics, Pennsylvania State University, Pennsylvania 16802, USA; 3Department of Detistry, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; 4Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do 13496, Republic of Korea; 5Department of Dental Education, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea; 6Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea; 7The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Barco, Guimarães, Portugal Background: For effective bone regeneration, it is necessary to implant a biocompatible scaffold that is capable of inducing cell growth and continuous osteogenic stimulation at the defected site. Here, we suggest an injectable hydrogel system using enzymatic cross-linkable gelatin (Gel) and functionalized gold nanoparticles (GNPs). Methods: In this work, tyramine (Ty) was synthesized on the gelatin backbone (Gel-Ty) to enable a phenol crosslinking reaction with horseradish peroxidase (HRP). N-acetyl cysteine (NAC) was attached to the GNPs surface (G-NAC) for promoting osteo-differentiation. Results: The Gel-Ty hydrogels containing G-NAC (Gel-Ty/G-NAC) had suitable mechanical strength and biocompatibility to embed and support the growth of human adipose derived stem cells (hASCs) during a proliferation test for three days. In addition, G-NAC promoted osteo-differentiation both when it was included in Gel-Ty and when it was used directly in hASCs. The osteogenic effects were demonstrated by the alkaline phosphatase (ALP) activity test. Conclusion: These findings indicate that the phenol crosslinking reaction is suitable for injectable hydrogels for tissue regeneration and G-NAC stimulate bone regeneration. Based on our results, we suggest that Gel-Ty/G-NAC hydrogels can serve both as a biodegradable graft material for bone defect treatment and as a good template for tissue engineering applications such as drug delivery, cell delivery, and various tissue regeneration uses. Keywords: nanomaterial, gelatin, enzymatic cross-linking, osteogenesis, N-acetyl cysteine

Keywords

• Nanomaterial
• Gelatin
• Enzymatic cross-linking
• Osteogenesis
• N-acetyl cysteine.