Development of a multifunctional nanodendrimer system for bone injury treatment
Dendrimers, with their highly branched architecture consisting of a hydrophobic core and a hydrophilic shell, have long been utilised as nanoscale “drug reservoirs” in various biomedical applications. They have proven effective in cancer therapy, wound healing, dentistry, and tissue engineering due to their ability to encapsulate drugs via electrostatic interactions or internal cavities, enabling controlled and sustained drug release. However, challenges remain in terms of drug-loading capacity and precise release control. Moreover, attaching drugs directly to the dendrimer surface can compromise secondary biological functions, which rely on the availability of free surface functional groups.
To address this, a research task funded by the Vietnam Academy of Science and Technology titled “Development of a multifunctional dendrimer system using animal-shell-inspired encapsulation methods to enhance bone regeneration” (code: QTKR01.01/23-24) was initiated with the hope of bringing a breakthrough in the treatment of bone damage. The project is part of a collaboration with the National Research Foundation of the Republic of Korea (NRF), co-led by Prof. Dr. Nguyen Cuu Khoa, former Director of the Institute of Applied Materials Science (now the Institute of Advanced Technology), and Prof. Dr. Jinkee Hong from Yonsei University, the Republic of Korea. The study exploits the branched structure of dendrimers – with a hydrophobic core and hydrophilic exterior – to both carry and release anti-inflammatory agents and osteogenic stimulants in a controlled manner, directly at the site of bone defects.
Prof. Dr. Nguyen Cuu Khoa in the laboratory
In this study, the researchers developed a dendrimer system with dual biological activity: encapsulating the anti-inflammatory drug dexamethasone while simultaneously integrating osteogenic ions and factors to promote biomineralisation in bone defects. This approach combines Vietnam's expertise in multifunctional dendrimer synthesis and its partner's strengths in biomaterials, paving the way for a breakthrough in bone regeneration therapies. Key supporting technologies include: a dual-phase calcium phosphate system capable of delivering BMP-2, enhancing bone regeneration by 2.76 times; Ca²⁺/PO₄³⁻ ion release for enamel remineralisation; and a zwitterionic network with di-tyrosine bonding to improve the mechanical-biological properties of polymers. This partnership aims to provide lasting benefits for the healthcare systems of both countries.
(a) Illustration of the formation and chemical structure of the multifunctional dendrimer system inspired by animal-shell mimicry. (b) Bone regeneration efficacy of the dendrimer system based on the synergistic effects of HAp and slow-releasing anti-inflammatory drugs
The synthesis of PAMAM G3.5 was confirmed via ¹H NMR spectroscopy and mass spectrometry (MS), validating its structure and molecular weight. Encapsulation of DEX using cyclodextrin improved drug retention compared to free DEX and enabled a more stable, slower release profile.
Synthesis and characterisation of PAMAM G3.5 dendrimer with EDA core, including: synthesis schematic (a), ¹H NMR spectrum (b), FT-IR spectrum (c), TEM images showing morphology (d-e), hydrodynamic size via DLS (f), and zeta potential (g)
According to Prof. Dr. Nguyen Cuu Khoa, rather than focusing on a single function, the research group aimed to design a dendrimer system with dual biological activity – both effective anti-inflammatory action and stimulation of osteogenesis. This integrated approach is expected to significantly improve the treatment of complex bone injuries. In the future, the team intends to develop new dendrimer versions incorporating bioactive compounds from Vietnamese medicinal plants, capitalising on local resources to enable broader and more sustainable applications suitable for Vietnam’s long-term treatment needs.
The successful synthesis of PAMAM G3.5 with accurate structure and molecular mass forms a crucial foundation for advanced drug delivery systems. Preliminary results using the DEX-loaded dendrimer system show stable drug retention and release, suitable for chronic disease treatment. Especially when combined with hydroxyapatite, the material system has shown promising potential to promote bone regeneration. This lays the groundwork for further research into improving treatments for musculoskeletal injuries in regenerative medicine.
In vitro experiments: (a) Biocompatibility assessment of G3.5/CD@DEX on L929 cells, (b) Live/dead fluorescence staining of L929 cells after incubation with G3.5/CD@DEX, (c) Haemolytic activity of G3.5/CD and G3.5/CD@DEX formulations, (d) Particle size and zeta potential changes of G3.5/CD@DEX after incubation with BSA for 1–24 hours, (e) NO production inhibition by G3.5/CD@DEX in RAW 264.7 cells.
This research opens up a practical and sustainable direction for applying nanotechnology in medicine, with promising long-term benefits for the community. The team published their findings in the prestigious Journal of Molecular Structure, confirming the potential of dendrimer systems in inflammation treatment and drug delivery. The study also significantly enhanced the research team’s expertise in dendrimer synthesis and application. Collaboration with Yonsei University under the NRF framework (2022–2024) has strengthened Vietnam–the Republic of Korea research ties and laid the groundwork for future projects.
Building on this success, the scientists hope to expand cooperation to develop new dendrimer versions integrating multiple bioactive compounds. Of particular interest is the incorporation of extracts from Vietnamese medicinal plants, harnessing local materials to increase the scientific and economic value of traditional remedies. The next phase of research will focus on evaluating the effectiveness of natural compound-loaded dendrimers in chronic bone-related diseases. At the same time, the team will explore dendrimer material variants to further improve efficacy and biocompatibility under real-world clinical conditions.
Translated by Phuong Huyen
Link to Vietnamese version
