Porous PLGA microspheres tailored for dual delivery of biomolecules via layer‐by‐layer assembly

Abstract

Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (α-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. α-MSH and bFGF were released in a sustained manner and the bioactivity of α-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules.

Multilayered pore‐closedPLGAmicrosphere deliveringOGPandBMP‐2 in sequential release patterns for the facilitation ofBMSCs osteogenic differentiation

“…), denoted as PMs (OGP/BMP‐2). As previously reported, the deposition of 5.5 bilayers were selected to ensure the formation of more uniform coating on the PLGA microspheres and reduce BMP‐2 leakage for subsequent a significantly lower release rate constants. Hep was added to facilitate the binding of BMP‐2 to the polyelectrolyte layers and maintain its bioactivity .…”

Porous microspheres support mesenchymal progenitor cell ingrowth and stimulate angiogenesis

“…As a three-dimensional (3D) cell support matrix for cells, porous microspheres have many advantages over their non-porous counterparts; they can provide enhanced nutrient diffusion, a 3D culture environment, and a greatly increased surface area. 16,17 There are many techniques to manufacture porous microsphere systems including supercritical CO 2 , 18 thermally induced phase separation, 19 freeze thaw cycles, 20 particle leaching, 21 and polymerised high internal phase emulsion (polyHIPE) formulations. 22 PolyHIPE fabrication methods are of particular interest because of the extremely high interconnected porosity achievable with this system.…”

Delivery strategies to control inflammatory response: Modulating M1–M2 polarization in tissue engineering applications

“…The short-term in vitro effects and weak in vivo effects were hypothesized to be due to the rapid release of α-MSH. Thus, O'Connor and co-workers modified their system to prolong the release of α-MSH by decreasing the diffusion rate [74]. Specifically, they made porous PLGA microspheres, physically adsorbed α-MSH, and also added polyelectrolyte layers with embedded fibroblast growth factor (FGF) on top of the α-MSH.…”