title: Injectable Peptide Decorated Functional Nanofibrous Hollow Microspheres to Direct Stem Cell Differentiation and Tissue Regeneration.
abstract: Injectable microspheres are attractive stem cell carriers for minimally invasive procedures. For tissue regeneration, the microspheres need to present the critical cues to properly direct stem cell differentiation. In natural extracellular matrix (ECM), growth factors (GFs) and collagen nanofibers provide critical chemical and physical cues. However, there have been no reported technologies that integrate synthetic nanofibers and GFs into injectable microspheres. In this study, we synthesized functional nanofibrous hollow microspheres (FNF-HMS), which can covalently bind GF-mimicking peptides. Two different GF-mimicking peptides, Transforming Growth Factor-β1 mimicking peptide Cytomodulin (CM) and Bone Morphogenetic Protein-2 mimicking peptide P24, were separately conjugated onto the FNF-HMS to induce distinct differentiation pathways of rabbit bone marrow-derived mesenchymal stem cells (BMSCs). While no existing biomaterials were reported to successfully deliver CM to induce chondrogenesis, the developed FNF-HMS were shown to effectively present CM to BMSCs and successfully induced their chondrogenesis for cartilage formation in bothin vitroandin vivostudies. In addition, P24 was conjugated onto the newly developed FNF-HMS and was capable of retaining its bioactivity and inducing ectopic bone formation in nude mice. These results demonstrate that the novel FNF-HMS can effectively deliver GF-mimicking peptides to modulate stem cell fate and tissue regeneration.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109-1078.
authors.forename: Zhanpeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109-1078.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Gupte
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109-1078.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109-1078 ; Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109-1078 ; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109-1078 ; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, 48109-1078.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
keywords: Bioconjugation; Functional nanofibrous hollow microsphere; Growth factor mimics; Stem cell; Tissue engineering