Controlling Adult Stem Cell Behavior Using Nanodiamond-Reinforced Hydrogel: Implication in Bone Regeneration Therapy

Abstract

Nanodiamonds (NDs) have attracted considerable attention as drug delivery nanocarriers due to their low cytotoxicity and facile surface functionalization. Given these features, NDs have been recently investigated for the fabrication of nanocomposite hydrogels for tissue engineering. Here we report the synthesis of a hydrogel using photocrosslinkable gelatin methacrylamide (GelMA) and NDs as a three-dimensional scaffold for drug delivery and stem cell-guided bone regeneration. We investigated the effect of different concentration of NDs on the physical and mechanical properties of the GelMA hydrogel network. The inclusion of NDs increased the network stiffness, which in turn augmented the traction forces generated by human adipose stem cells (hASCs). We also tested the ability of NDs to adsorb and modulate the release of a model drug dexamethasone (Dex) to promote the osteogenic differentiation of hASCs. The ND-Dex complexes modulated gene expression, cell area, and focal adhesion number in hASCs. Moreover, the integration of the ND-Dex complex within GelMA hydrogels allowed a higher retention of Dex over time, resulting in significantly increased alkaline phosphatase activity and calcium deposition of encapsulated hASCs. These results suggest that conventional GelMA hydrogels can be coupled with conjugated NDs to develop a novel platform for bone tissue engineering.

Deciphering the role of substrate stiffness in enhancing the internalization efficiency of plasmid DNA in stem cells using lipid-based nanocarriers

“…Paxillin staining was carried out to investigate the differences in cell focal adhesion expression. 23 A greater focal adhesion area was observed for the hASCs seeded on the stiff hydrogels, and this result is congruent with previous reports that investigated paxillin expression in other cells lines (Figure 1C). 24 Aside from a change in the focal adhesion area, a higher number of actin stress fibers was quantified in the hASCs on the 32 kPa hydrogels (Figure 1D).…”

Adoption of nanodiamonds as biomedical materials for bone repair

“…This advantage has encouraged scientists to investigate NDs for a broad range of applications [8] in regenerative medicine with a primary focus on bone tissue engineering. NDs possess versatile surface functionalities and they can be loaded with virtually any type of biomolecule, thereby enabling their use as delivery vehicles in bone-healing applications [9]. The presence of surface functional groups can efficiently control the interfacial reactions between the nanoparticle and the active biomolecule, eventually maximizing the therapeutic efficiency of the delivered biomaterial.…”

Fabrication of a Double-Cross-Linked Interpenetrating Polymeric Network (IPN) Hydrogel Surface Modified with Polydopamine to Modulate the Osteogenic Differentiation of Adipose-Derived Stem Cells

“…Alkaline phosphatase (ALP) expression was evaluated at 7 and 14 days based on our previous study, demonstrating that the maximum expression of the ALP gene in hASCs is observed after 14 days of culture in osteogenic medium. 28 Staining of ALP revealed a more-significant presence of the enzyme in the hASCs cultured on the Dex group compared to the system of pDA/Dex at day 7. This difference may be due to the larger desorption of the drug observed from the hydrogel that did not possess a pDA layer, which resulted in a higher presence of dexamethasone in the media.…”