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

Abstract

Bone tissue regeneration may be more effectively administrated by controlled release of multiple biofactors, given that bone healing comprises a cascade of biological events controlled by numerous cytokines and growth factors (GFs). Here, we propose a novel microcarrier with the capability to sequentially deliver dual biofactors for better controlling the bone regeneration process. First, osteogenic growth peptide (OGP) was incorporated in porous poly(lactic-co-glycolic) acid (PLGA) microspheres by a simple solution dipping method and subsequent pore-closing treatment. Then, a multilayered polyelectrolyte coating ((HA-CS) 2 -Hep-BMP-2-Hep-(CS-HA) 2 ) was prepared on the surface of such OGP-loaded pore-closed PLGA microspheres by layer-by-layer assembly. Results showed that the OGP release was minimal (<17.1%) in the first 15 days but accelerated remarkably thereafter, while at least 60.3% of the bone morphogenetic protein-2 (BMP-2) load was released in the first 15 days and only very slow release was observed subsequently. Further in vitro cell experiments showed that the dual-biomolecule-loaded microspheres elicited more cells with extremely elongated cellular morphology, much higher alkaline phosphatase level and upregulated expression of osteocalcin. Such a dual loading of OGP and BMP-2 had a more positive impact on bone marrow mesenchymal stem cells proliferation and osteogenic differentiation compared with either OGP or BMP-2 alone, suggesting potential synergistic benefit of the sequential release of multiple peptide-based biofactors in a coordinated manner. Overall, this dual delivery system may provide a therapeutic strategy sequentially targeting multiple events (or mechanisms) during bone healing, which is believed to benefit the regenerative repair of bone defects.

Regeneración ósea como un ejemplo de ingeniería tisular en odontología, con énfasis en el desarrollo de los andamios

“…La segunda, aumenta la proliferación y actividad de los osteoblastos, acelerando así la osificación y la formación de la matriz ósea, efecto conocido como modulación. Ambos, inducción y modulación, funcionan de manera sinérgica (14,18,21,22,23) (Tabla 2).…”

Sandwich-structure hydrogels implement on-demand release of multiple therapeutic drugs for infected wounds

“…10,11 Such effects are also achieved using multilayer nanoparticles or microparticles and compartmental nanobers. [12][13][14][15] These drug releasing systems share the similar principle that drugs loaded in the inner layer are released more slowly than those in the outer layer. In addition, the drugs themselves can affect releasing dynamics due to the differences of drug structure, hydrophilia and molecular weight, [16][17][18] which consequently lead to phased drug release.…”

Microspheres with Tunable Porosity Based on Reactive Block Copolymer: Preparation and Vapor‐Healing Behavior

“…The main Porous microspheres (PMS) have found their application in drug delivery, adsorption and separation, catalysis, and cargo for small molecules, due to their high specific surface area, high permeability, stability, and low density. Particularly, healable PMS attracted special attention because of their unique advantages in guest carrying and control release . The strategy to prepare PMS usually includes: PMS formed during the copolymerization of hydrophobic and partially hydrophilic monomers, selective swelling followed by evaporating or etching of partial component of microspheres, and drying of multiple emulsion stabilized by partially hydrophilic polymers .…”