Engineering the Ratios of Nanoparticles Dispersed in Triphasic Nanocomposites for Biomedical Applications

Cheyann Wetteland; Changlu Xu; Sebo Michelle Wang; Chaoxing Zhang; Elizabeth Juntilla Ang; Cole Gabriel Azevedo; Huinan Hannah Liu

doi:10.1021/acsami.4c14712

Engineering the Ratios of Nanoparticles Dispersed in Triphasic Nanocomposites for Biomedical Applications

ACS Appl Mater Interfaces. 2025 Jan 6. doi: 10.1021/acsami.4c14712. Online ahead of print.

Authors

Cheyann Wetteland¹, Changlu Xu², Sebo Michelle Wang¹, Chaoxing Zhang², Elizabeth Juntilla Ang¹, Cole Gabriel Azevedo², Huinan Hannah Liu^{1

2

3}

Affiliations

¹ Department of Bioengineering, University of California, Riverside, 900 University Avenue, Riverside, California 92521, United States.
² Materials Science and Engineering Program, University of California, Riverside, 900 University Avenue, Riverside, California 92521, United States.
³ Stem Cell Center, University of California, Riverside, 900 University Avenue, Riverside, California 92521, United States.

PMID: 39761195
DOI: 10.1021/acsami.4c14712

Abstract

Polymer/ceramic nanocomposites integrated the advantages of both polymers and ceramics for a wide range of biomedical applications, such as bone tissue repair. Here, we reported triphasic poly(lactic-co-glycolic acid) (PLGA, LA/GA = 90:10) nanocomposites with improved dispersion of hydroxyapatite (HA) and magnesium oxide (MgO) nanoparticles using a process that integrated the benefits of ultrasonic energy and dual asymmetric centrifugal mixing. We characterized the microstructure and composition of the nanocomposites and evaluated the effects of the HA/MgO ratios on degradation behavior and cell-material interactions. The PLGA/HA/MgO nanocomposites were composed of 70 wt % PLGA and 30 wt % nanoparticles made of 20:10, 25:5, and 29:1% by weight of HA and MgO, respectively. The results showed that the nanocomposites had a homogeneous nanoparticle distribution and as-designed elemental composition. The cell study indicated that reducing the MgO content in the triphasic nanocomposite increased the BMSC adhesion density under both direct and indirect contact conditions. Specifically, after the 24 and 48 h of culture, the PLGA/HA/MgO group with a weight ratio of 70:29:1 (P70/H29/M1) exhibited the greatest average cell adhesion density under direct and indirect contact conditions among triphasic nanocomposites. During a 28-day degradation study, the mass loss of triphasic nanocomposites was 18 ± 2% for P70/H20/M10, 9 ± 2% for P70/H25/M5, and 7 ± 1% for P70/H29/M1, demonstrating that MgO nanoparticles accelerated the degradation of the nanocomposites. Postculture analysis showed that the pH values and Mg²⁺ ion concentrations in the media increased with increasing MgO content in the nanocomposites. Triphasic nanocomposites provided different degradation profiles that can be tuned for different biomedical applications, especially when a shorter or longer period of degradation would be desirable for optimal bone tissue regeneration. The concentration and ratio of nanoparticles should be adjusted and optimized when other polymers with different degradation modes and rates are used in the nanocomposites.

Keywords: biodegradation; bone marrow-derived mesenchymal stem cells (BMSCs); cell–material interactions; hydroxyapatite (HA); magnesium oxide (MgO); poly(lactic-co-glycolic acid) (PLGA); triphasic nanocomposites.