On the use of dexamethasone-loaded liposomes to induce the osteogenic differentiation of human mesenchymal stem cells

Abstract

Stem cells have received considerable attention by the scientific community because of their potential for tissue engineering and regenerative medicine. The most frequently used method to promote their differentiation is supplementation of the in vitro culture medium with growth/differentiation factors (GDFs). The limitations of that strategy caused by the short half-life of GDFs limit its efficacy in vivo and consequently its clinical use. Thus, the development of new concepts that enable the bioactivity and bioavailability of GDFs to be protected, both in vitro and in vivo, is very relevant. Nanoparticle-based drug delivery systems can be injected, protect the GDFs and enable spatiotemporal release kinetics to be controlled. Liposomes are well-established nanodelivery devices presenting significant advantages, viz. a high load-carrying capacity, relative safety and easy production, and a versatile nature in terms of possible formulations and surface functionalization. The main objective of the present study was to optimize the formulation of liposomes to encapsulate dexamethasone (Dex). Our results showed that the optimized Dex-loaded liposomes do not have any cytotoxic effect on human bone marrow-derived mesenchymal stem cells (hBMSCs). More importantly, they were able to promote an earlier induction of differentiation of hBMSCs into the osteogenic lineage, as demonstrated by the expression of osteoblastic markers, both phenotypically and genotypically. We concluded that Dex-loaded liposomes represent a viable nanoparticle strategy with enhanced safety and efficacy for tissue engineering and regenerative medicine.

Nanoparticles for bone tissue engineering

“…SEM images of liposomes (A, adapted from Ref. , with permission from John Wiley & Sons) and polyester NPs (B, adapted from Ref. , with permission from John Wiley & Sons).…”

“…Such bivalent systems are then able to support cells and also provide growth and differentiation factors . Studies using several types of NPs such as polymeric, liposomes, silica, and calcium phosphate ceramic NPs indicated that the use of nanoparticulate systems as carriers allow a sustained delivery of their cargo. Table summarizes the outcomes of NPs used as drug and gene carriers.…”

“…In vivo studies in rat revealed the effective osteoblast differentiation and bone regeneration after 3 weeks of intramuscular implantation. Liposomes were also reported as carriers for Dex intracellular delivery, promoting earlier osteogenic differentiation of human bone marrow MSCs without cytotoxicity . Liposomes are also being used for the delivery of other components, such as antibacterial drugs that can be released within scaffolds to inhibit the growth of bacterial biofilms, and for epidermal growth factor (EGF) delivery on rat tooth sockets.…”

Liposomes in tissue engineering and regenerative medicine

“…An adequate combination of signalling molecules should be provided by controlled release systems in order to promote the desired regenerative outcome [112,[157][158][159]. Therefore, liposomes can be used as carriers for the spatio-temporal controlled delivery of GFs, improving stem cell proliferation and differentiation in vitro [160,161].…”

Influence of PDLA nanoparticles size on drug release and interaction with cells

“…Indeed, the use of these structured biomaterials as delivery devices allows surpassing solubility problems of the therapeutic agents, leading to reduced systemic toxicity and tissue damage . Additionally, they can be designed to protect drugs, peptides, proteins and nucleic acids from premature degradation and undesirable interactions with the biological environment, preserving its bioavailability for longer periods of time . The undesirable side effects in surrounding healthy tissues, due to drug distribution throughout the entire organism, can also be circumvented by delivering therapeutic agents into a specific organ or tissue, using antibodies, peptides or other targeting moieties linked to the surface of the delivery devices …”