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.
Highlights
Bones are a rigid and complex form of connective tissue that is constantly created and renewed throughout life
In our previous work, we identified the conditions promoting the highest incorporation of growth factors (GFs) and osteogenic differentiation of human mesenchymal stem cells [16], we further characterize the optimal assembly in terms of osteogenic and angiogenic potential
While Bone morphogenetic protein-2 (BMP-2) is a well-known, FDA-approved osteogenic GF, vascular endothelial growth factor (VEGF) plays a central role in angiogenesis, promoting vascularized bone regeneration
Summary
Bones are a rigid and complex form of connective tissue that is constantly created and renewed throughout life. We have previously reported the fabrication of PCL/HA-based scaffolds displaying a highly interconnected network of pores with a bimodal pore size distribution [15] Such an architecture mimics the extracellular matrix of natural bone tissue. We fabricate highly interconnected porous PCL/HA composite scaffolds with a bimodal pore size distribution which are subsequently coated by two independent PDA layers loaded with the two GFs (Scheme 1). Following assembly and characterization of the surface coatings, we evaluate the potential of the scaffolds for BTE applications in terms of the angiogenic and osteogenic gene expression in a co-culture system of hMSCs and human EPCs (hEPCs) This is an important aspect since, the interplay between vessel-forming endothelial cells and bone-forming cells is a crucial aspect in bone healing, involving several and interconnected steps overlapping in time [27]. Npeoxlyt,daonpianmteirnceon(PnDecAti)nlgaydeirthiinoclolrapyoeraitsindgepthoesigterdow(itihi) ftaocatollrowbofnoer mcooartpinhgogweinthetaicspecrotnedinP-2D(ABMlaPye)-r2 c(oini)t.aNineixntg, athneivnatesrccuolnarnenctdinogthdeliitahlioglrolawytehr fiascdtoerp(oVsiEteGdF)(igiir)otwotahllfoawctofro(rivco).aTtihnegcwoaitthedassceacffoonlddsPaDreA elvaayleuratceodnbtayincoin-cgultthuerinvgashcuumlaarnemndeosethnechliyalmgalroswtemth cfealclsto(hr M(VSECGs)Fa)ndgrhouwmthanfaecntdoorth(ievli)a. lTphroegceonaittoerd cseclalsff(ohlEdPsCasr)e(ve)vaanludabtyedasbseysscino-gcuthlteuiridnigffehreunmtiaantiomn einsetoncbhoynme-aflorsmteimng acenldlsve(hssMelS-Cfosr)maingd chelulsmbayn geenndeoetxhperlieaslspiornog(veni)i.tor cells (hEPCs) (v) and by assessing their differentiation into bone-forming and vessel-forming cells by gene expression (vi)
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