Polydopamine-Assisted Osteoinductive Peptide Immobilization of Polymer Scaffolds for Enhanced Bone Regeneration by Human Adipose-Derived Stem Cells

Abstract

Immobilization of osteoinductive molecules, including growth factors or peptides, on polymer scaffolds is critical for improving stem cell-mediated bone tissue engineering. Such molecules provide osteogenesis-stimulating signals for stem cells. Typical methods used for polymeric scaffold modification (e.g., chemical conjugation or physical adsorption), however, have limitations (e.g., multistep, complicated procedures, material denaturation, batch-to-batch inconsistency, and inadequate conjugation) that diminish the overall efficiency of the process. Therefore, in this study, we report a biologically inspired strategy to prepare functional polymer scaffolds that efficiently regulate the osteogenic differentiation of human adipose-derived stem cells (hADSCs). Polymerization of dopamine (DA), a repeated motif observed in mussel adhesive protein, under alkaline pH conditions, allows for coating of a polydopamine (pDA) layer onto polymer scaffolds. Our study demonstrates that predeposition of a pDA layer facilitates highly efficient, simple immobilization of peptides derived from osteogenic growth factor (bone morphogenetic protein-2; BMP-2) on poly(lactic-co-glycolic acid) (PLGA) scaffolds via catechol chemistry. The BMP-2 peptide-immobilized PLGA scaffolds greatly enhanced in vitro osteogenic differentiation and calcium mineralization of hADSCs using either osteogenic medium or nonosteogenic medium. Furthermore, transplantation of hADSCs using pDA-BMP-2-PLGA scaffolds significantly promoted in vivo bone formation in critical-sized calvarial bone defects. Therefore, pDA-mediated catechol functionalization would be a simple and effective method for developing tissue engineering scaffolds exhibiting enhanced osteoinductivity. To the best of our knowledge, this is the first study demonstrating that pDA-mediated surface modification of polymer scaffolds potentiates the regenerative capacity of human stem cells for healing tissue defect in vivo.

Control of stem cell fate by engineering their micro and nanoenvironment

“…Curran et al [66] Peptide sequence Alginate Osteopontin peptide Increase in hMSC osteogenic markers Lee et al [67] HA-PLG Osteocalcin peptide Increase hMSC osteogenic markers Lee et al [68] PLGA BMP-2 peptide Increase rMSC ALP expression in osteogenic medium and promotion of ectopic bone formation in vivo Lin et al [15] RGD BCP/PLA hMSC osteogenic differentiation Shin et al [70] Molecule PLGA BMP-2 hMSC osteogenic differentiation Ko et al [71] PLLA BMP-2 hMSC osteogenic differentiation Beazley et al [16] Collagen-PLGA hybrid Collagen-binding domain derived from fibronectin (CBD-BMP4) hMSC osteogenic differentiation Lu et al [72] Methacrylamide chitosan hydrogel coated glass substrates Laminin and collagen Supported hNSC differentiation Wilkinson et al [73] PMMA-g-PEG EGF MSC osteogenic differentiation Platt et al [74] Agarose PDGF-AA MSC neural differentiation Aizawa et al [75] PCL/PCL-PEG NGF MSC neural differentiation Cho et al [76] Chitosan/collagen Ⅳ VEGF Endothelial differentiation Chiang et al [77] , Poh et al [78] , Rahman et al [79] hESC: Human embryonic stem cell; hMSC: Human mesenchymal stem cell; rMSCs: Rat mesenchymal stem cell; hNSC: Human neural stem cell; PEG: Polyethylene glycol; HA-PLG: Hydroxyapatite (HA)/poly(lactic-co-glycolic acid); BMP: Bone morphogenetic protein; PLGA: Poly(lactic-co -g lycolic acid); PLA: Poly(lactic acid); PLLA: Poly(L-lactide); PCL: Polycaprolactone; PMMA-g-PEG: Poly(methyl methacrylate)-graft-poly(ethylene glycol; BCP: Biphasic calcium phosphate; EGF: Epidermal growth factor; NGF: Nerve growth factor; PDGF-AA: Platelet-derived Growth Factor AA; VEGF: Vascular endothelial growth factor.…”

Effect of Titanium Surface Modifications of Dental Implants on Rapid Osseointegration

“…Eight weeks later, the modifi ed materials exhibited enhanced new bone formation around the bone defects. In another animal experiment, human adipose-derived stem cells (hADSCs) cultured on the PDA and BMP-2-modifi ed PLGA scaffold were implanted in mice skull defects, and the modifi ed materials were also found to effectively enhance new bone formation [ 56 ]. It is reported that PDA coating is a biocompatible coating which can be reduced by PDA-modifi ed PLLA of infl ammation and immune responses [ 57 ].…”

The Effects of <b><i>Hypericum perforatum</i></b> L. on the Proliferation, Osteogenic Differentiation, and Inflammatory Response of Mesenchymal Stem Cells from Different Niches

“…Osteoinductive agents aim to stimulate seeded cell migration, proliferation, and migration, and modulate immune responses, involving the stimulation of MSCs and/or osteoprogenitors to differentiate into osteoblasts. There are many osteogenic proteins that stimulate the proliferation and differentiation of MSCs and/or progenitors in vitro and in vivo [Govender et al, 2002;Giannoudis et al, 2005;Ko et al, 2013]. However, they have a short half-life, and so require either high concentrations or sustained delivery for bone tissue engineering [Itoh et al, 2001].…”