The effect of incorporation of SDF-1α into PLGA scaffolds on stem cell recruitment and the inflammatory response

Abstract

Despite significant advances in the understanding of tissue responses to biomaterials, most implants are still plagued by inflammatory responses which can lead to fibrotic encapsulation. This is of dire consequence in tissue engineering, where seeded cells and bioactive components are separated from the native tissue, limiting the regenerative potential of the design. Additionally, these interactions prevent desired tissue integration and angiogenesis, preventing functionality of the design. Recent evidence supports that mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC) can have beneficial effects which alter the inflammatory responses and improve healing. The purpose of this study was to examine whether stem cells could be targeted to the site of biomaterial implantation and whether increasing local stem cell responses could improve the tissue response to PLGA scaffold implants. Through incorporation of SDF-1α through factor adsorption and mini-osmotic pump delivery, the host-derived stem cell response can be improved resulting in 3X increase in stem cell populations at the interface for up to 2 weeks. These interactions were found to significantly alter the acute mast cell responses, reducing the number of mast cells and degranulated mast cells near the scaffold implants. This led to subsequent downstream reduction in the inflammatory cell responses, and through altered mast cell activation and stem cell participation, increased angiogenesis and decreased fibrotic responses to the scaffold implants. These results support that enhanced recruitment of autologous stem cells can improve the tissue responses to biomaterial implants through modifying/bypassing inflammatory cell responses and jumpstarting stem cell participation in healing at the implant interface.

Harnessing and Modulating Inflammation in Strategies for Bone Regeneration

“…10 SDF-1 delivery from subcutaneously implanted PLGA scaffolds significantly reduced in vivo fibrotic encapsulation and inflammatory cell accumulation near the scaffold, 10 demonstrating the potential of this cytokine as a component of future immunomodulatory strategies to prevent foreign body reactions to biomedical implants.…”

Real-time detection of implant-associated neutrophil responses using a formyl peptide receptor-targeting NIR nanoprobe

“…34,35 Hematoxylin and eosin staining was performed on all samples to assess the overall inflammatory reactions. To quantify the number of recruited neutrophils, some tissue sections were immunohistochemically stained with pan-neutrophil antibody (Santa Cruz Biotechnology, Santa Cruz, CA) and then with peroxidase-conjugated goat anti-rat secondary antibodies (Jackson ImmunoResearch Laboratories, West Grove, PA).…”

The Fibrotic Response to Implanted Biomaterials: Implications for Tissue Engineering

“…Given that chemokines regulate cell trafficking (Gerard & Rollins, 2001) and play a key role in the recruitment of inflammatory cells in the peritoneal foreign body response (Luttikhuizen et al, 2007), chemokines may be an important target for intervention. De Visscher et al (2010) have shown that impregnation of bioprosthetic heart valves with SDF-1 and fibronectin modulated the cellular response to produce more biologically relevant tissue with properties very similar to native valves, whilst Thevenot et al (2010) showed that delivery of SDF-1 to the site of biomaterial implantation increased the recruitment of host stem cells, and at the same time reduced the inflammatory response, such that the fibrotic response to scaffold implants was ameliorated. They suggested that enhanced recruitment of autologous stem cells can improve the tissue responses to biomaterial implants through modifying/bypassing inflammatory cell responses and stimulating stem cell participation in healing at the implant interface.…”