Abstract
Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3–4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. Both in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds.
Highlights
Bone regeneration is a complex cascade of biological events controlled by numerous bioactive molecules that provide signals at local injury sites allowing progenitors and inflammatory cells to migrate and trigger healing processes
The results reveal that scaffolds engrafted with NPTH and induced modified alkaline phosphatase (ALP) levels post seeded with hFOB cells, which increased as the treatment time increased (Figure 12a)
parathyroid hormone (PTH) (1–34) with that of total PTH (1–34) obtained from nanoparticles and released PTH (1–34) at different time intervals such as 1, 4 and 8 h on cyclic adenosine monophosphate (cAMP) production in hFOB cells cultured in growth medium as a tool to detect the in vitro bio activity. These results indicate that PTH (1–34) loaded nanoparticles prepared by this method retained PTH (1–34) activity after the formulation and during the release
Summary
Bone regeneration is a complex cascade of biological events controlled by numerous bioactive molecules that provide signals at local injury sites allowing progenitors and inflammatory cells to migrate and trigger healing processes. Conventional tissue engineering strategies utilise combination of cells, biodegradable scaffolds and systemic administration of bioactive molecules to promote natural processes of tissue regeneration and development [1]. One of the most common methods of creating controlled and localised release is to utilise the physical properties of the scaffolds. This can be achieved by simple mixing of the target biomolecules with the materials during scaffold fabrication [7]. In such systems, the properties of the scaffold, such as pore size or crosslinking density could regulate their release rate by diffusion.
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