title: Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds.
abstract: Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of a model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of the drug over the period of 28days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in the culture medium. The formation of a mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration.
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston 02115, USA; Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA; Department of Biomedical Engineering, Texas A&M University, College Station 77843, USA; Department of Materials Science & Engineering, Texas A&M University, College Station 77843, USA.
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Gaharwar
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA; 3B's Research Group, Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, University of Minho, AvePark, Taipas, 4806-909 Guimarães, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Mihaila
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: Ashish A
authors.initials: AA
authors.lastname: Kulkarni
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: Alpesh
authors.initials: A
authors.lastname: Patel
authors.affiliation: Tissue Regeneration Department, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, Netherlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Luca
authors.affiliation: 3B's Research Group, Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, University of Minho, AvePark, Taipas, 4806-909 Guimarães, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
authors.affiliation: 3B's Research Group, Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, University of Minho, AvePark, Taipas, 4806-909 Guimarães, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
authors.forename: Manuela E
authors.initials: ME
authors.lastname: Gomes
authors.affiliation: Tissue Regeneration Department, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: van Blitterswijk
authors.affiliation: Tissue Regeneration Department, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, Netherlands. Electronic address: l.moroni@utwente.nl.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moroni
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston 02115, USA; Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA; Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia. Electronic address: alik@rics.bwh.harvard.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D005109:Extracellular Matrix; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D054457:Tissue Scaffolds
chemical_list: D003692:Delayed-Action Preparations; D011091:Polyesters; C041733:poly(1,4-butylene terephthalate); D011092:Polyethylene Glycols; D003907:Dexamethasone; D000469:Alkaline Phosphatase
keywords: Amphiphilic polymer; Drug release; Electrospinning; Fibrous scaffolds; Human mesenchymal stem cells