Nanoindentation for Monitoring the Time-Variant Mechanical Strength of Drug-Loaded Collagen Hydrogel Regulated by Hydroxyapatite Nanoparticles

Hyo Gi Jung; Dongtak Lee; Sang Won Lee; Insu Kim; Yonghwan Kim; Jae Won Jang; Jeong Hoon Lee; Gyudo Lee; Dae Sung Yoon

doi:10.1021/acsomega.1c00824

Nanoindentation for Monitoring the Time-Variant Mechanical Strength of Drug-Loaded Collagen Hydrogel Regulated by Hydroxyapatite Nanoparticles

ACS Omega. 2021 Mar 23;6(13):9269-9278. doi: 10.1021/acsomega.1c00824. eCollection 2021 Apr 6.

Authors

Hyo Gi Jung^{1

2}, Dongtak Lee¹, Sang Won Lee¹, Insu Kim¹, Yonghwan Kim^{1

2}, Jae Won Jang^{1

2}, Jeong Hoon Lee³, Gyudo Lee^{4

5}, Dae Sung Yoon^{1

2}

Affiliations

¹ School of Biomedical Engineering, Korea University, Seoul 02841, South Korea.
² Interdisciplinary Program in Precision Public Health, Korea University, Seoul 02841, South Korea.
³ Department of Electrical Engineering, Kwangwoon University, Seoul 01897, South Korea.
⁴ Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, South Korea.
⁵ Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, South Korea.

Abstract

Hydroxyapatite nanoparticle-complexed collagen (HAP/Col) hydrogels have been widely used in biomedical applications as a scaffold for controlled drug release (DR). The time-variant mechanical properties (Young's modulus, E) of HAP/Col hydrogels are highly relevant to the precise and efficient control of DR. However, the correlation between the DR and the E of hydrogels remains unclear because of the lack of a nondestructive and continuous measuring system. To reveal the correlations, herein, we investigate the time-variant behavior of E for HAP/Col hydrogels during 28 days using the atomic force microscopy (AFM) nanoindentation technique. The initial E of hydrogels was controlled from 200 to 9000 Pa by the addition of HAPs. Subsequently, we analyzed the relationship between the DR of the hydrogels and the changes in their mechanical properties (ΔE) during hydrogel degradation. Interestingly, the higher the initial E value of HAP/Col hydrogels is, the higher is the rate of hydrogel degradation over time. However, the DR of hydrogels with higher initial E appeared to be significantly delayed by up to 40% at a maximum. The results indicate that adding an appropriate amount of HAPs into hydrogels plays a crucial role in determining the initial E and their degradation rate, which can contribute to the properties that prolong DR. Our findings may provide insights into designing hydrogels for biomedical applications such as bone regeneration and drug-delivery systems.