Stem cell homing using local delivery of plerixafor and stromal derived growth factor‐1alpha for improved bone regeneration around Ti‐implants

Abstract

Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1α/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1α, from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1α were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2466-2475, 2016.

Local SDF-1α application enhances the therapeutic efficacy of BMSCs transplantation in osteoporotic bone healing

“…SDF-1α/CXCR4 signaling plays a pivotal role in the regulation of BMSCs homing and the engraftment of transplanted BMSCs for the design of innovative biomaterials and therapies to achieve regeneration of damaged tissues [27]. Analogously, local administration of SDF-1α has a stimulatory effect on stem cell recruitment to promote osteointegration of titanium implants in rat tibia [33]. Moreover, some researchers attempted to improve stem cell therapy by overexpressing Sdf-1α or Cxcr4 gene of BMSCs before transplantation [34,35].…”

Mesenchymal Stromal Cell-Based Bone Regeneration Therapies: From Cell Transplantation and Tissue Engineering to Therapeutic Secretomes and Extracellular Vesicles

“…Due to these complexities with viable cells and tissue transplantation, a number of investigations have also focused on enhanced mobilization and homing of endogenous cells (which has not been extensively investigated in the clinic) (Yao and Lane, 2015; Karlsson et al, 2016; Yao et al, 2016) and on novel, secretome-based therapeutic approaches. Whereas clinical translation of the whole secretome might prove challenging as well, re-constitution of major secreted growth factor components (e.g., by using recombinant proteins) in concentrations similar to those in the MSC secretome might recapitulate the therapeutic effects, as was recently demonstrated (Ogata et al, 2018).…”

The Critical Role of Cell Homing in Cytotherapeutics and Regenerative Medicine

“…Although a collagen scaffold with radially oriented channels effectively induced cell migration, the addition of SDF‐1 led to an improved outcome, enhancing osteochondral regeneration . Furthermore, local delivery of SDF‐1α and plerixa to target the chemotactic SDF‐1α/CXCR4 axis toward enhanced cell homing promoted osseointegration around titanium implants . All these cell‐homing‐based approaches allow injured or lost tissues to be regenerated by utilizing a target‐specific scaffold, often loaded with selected growth factors, that recruits endogenous host cells to the scaffold location without a need for outside cell manipulation and transplantation 48a,76c.…”