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 both in vitro and in vivo studies. 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.

Fine‐Tunable and Injectable 3D Hydrogel for On‐Demand Stem Cell Niche

“…Furthermore, the previous studies also had demonstrated that the viability of stem cells encapsulated in 3D hydrogel was greater than 2D plated stem cells. [13] Moreover, in vivo MSC maintenance was measured using IVIS for the reason that the local presence of MSCs over longterm remained MSCs enhanced their therapeutic efficiency. Basically, the in vivo biocompatibility of postfabrication with β-CD PPZ, and use of ratio-controlled Ad-peptides and MSCs was confirmed using hematoxylin and eosin (H&E) staining.…”

“…[12] Although there are various types of biocompatible and injectable stem cell scaffolds such as poly(lactic acid) derivate, [13] hyaluronic acid, [14] and supramolecular hydrogel, [15] the controlled differentiation of stem cells is of foremost importance to the attainment of the desired tissue construction. [12] Although there are various types of biocompatible and injectable stem cell scaffolds such as poly(lactic acid) derivate, [13] hyaluronic acid, [14] and supramolecular hydrogel, [15] the controlled differentiation of stem cells is of foremost importance to the attainment of the desired tissue construction.…”

Fluorescence light-up AIE probe for monitoring cellular alkaline phosphatase activity and detecting osteogenic differentiation

“…11 And specific differentiation factors (physical or chemical stimuli) are needed to accelerate the osteogenic differentiation and bone regeneration process. [12][13][14][15][16] During osteogenic differentiation, a series of enzymes, genes and proteins are up-regulated, which were identified as osteogenic markers to evaluate cell osteogenic differentiation. 17 Among them, alkaline phosphatase (ALP) has been identified as an important marker for osteogenic differentiation.…”

Hybrid microscaffold-based 3D bioprinting of multi-cellular constructs with high compressive strength: A new biofabrication strategy

“…microspheres and microfibrils30, fabricated from biodegradable polymeric materials such as polyesters23, polypeptides31, polysaccharides32, and their combinations33, could serve the same purpose in this context. The scaffolds provide 2D surfaces with pseudo-3D environment for the anchorage-dependent cells to adhere and proliferate.…”