Immobilization of BMP-2 and VEGF within Multilayered Polydopamine-Coated Scaffolds and the Resulting Osteogenic and Angiogenic Synergy of Co-Cultured Human Mesenchymal Stem Cells and Human Endothelial Progenitor Cells

Abstract

We have previously reported the fabrication of a polycaprolactone and hydroxyapatite composite scaffold incorporating growth factors to be used for bone regeneration. Two growth factors were incorporated employing a multilayered coating based on polydopamine (PDA). In particular, Bone morphogenetic protein-2 (BMP-2) was bound onto the inner PDA layer while vascular endothelial growth factor (VEGF) was immobilized onto the outer one. Herein, the in vitro release of both growth factors is evaluated. A fastest VEGF delivery followed by a slow and more sustained release of BMP-2 was demonstrated, thus fitting the needs for bone tissue engineering applications. Due to the relevance of the crosstalk between bone-promoting and vessel-forming cells during bone healing, the functionalized scaffolds are further assessed on a co-culture setup of human mesenchymal stem cells and human endothelial progenitor cells. Osteogenic and angiogenic gene expression analysis indicates a synergistic effect between the growth factor-loaded scaffolds and the co-culture conditions. Taken together, these results indicate that the developed scaffolds hold great potential as an efficient platform for bone-tissue applications.

Topography: A Biophysical Approach to Direct the Fate of Mesenchymal Stem Cells in Tissue Engineering Applications

“…Additionally, the porosity and connectivity among the pores are two important parameters. While high porosities of~80% are regarded as optimal for the regeneration of new bone, cell ingrowth is also highly dependent on the degree of connectivity among the pores [220][221][222][223][224]. Additionally, recent studies are also indicating that interconnected pores are necessary to allow for the circulation of nutrients, waste and to promote the migration of cells to the center of the implant [225,226].…”

A Dual Peptide Sustained-Release System Based on Nanohydroxyapatite/Polyamide 66 Scaffold for Synergistic-Enhancing Diabetic Rats’ Fracture Healing in Osteogenesis and Angiogenesis

“… Dashtimoghadam et al (2020) demonstrated conjugation of BMP-2 growth factor onto monodisperse polymeric microcarriers encapsulating VEGF growth factor, which displayed an additive effect on bone regeneration. Moreover, in the study of Godoy-Gallardo et al (2020) , BMP-2 was bound onto the inner polydopamine layer, whereas VEGF was immobilized onto the outer one, and the two growth factors played a synergistic effect on bone regeneration. Compared with a fast–slow VEGF growth factor delivery followed by a slow-sustained release of BMP-2 growth factor for normal bone in these two studies, we provide a favorable option that supplies BMP-2 and VEGF molecular signals in the form of peptides with greater advantage, and a burst-release followed by slow-sustained release mode of BMP-2 and VEGF peptides is better to fit the specific need of diabetic bone regeneration.…”

Advances in Growth Factor Delivery for Bone Tissue Engineering

“…During tissue regeneration, different GF profiles are present, and the multilayer biotechnology is an open venue that allows for building GF carriers with appropriate delivery kinetics that are able to simulate those GF profiles. For instance, a polydopamine multilayered coating was used to associate BMP-2 and VEGF, where BMP-2 was bound onto the inner layer and VEGF was bound onto the outer layer [ 141 ]. The authors reported a more rapid VEGF delivery succeeded by a gentle and more continuous release of BMP-2.…”