The promotion of mandibular defect healing by the targeting of S1P receptors and the recruitment of alternatively activated macrophages
| Autor: | Claire E. Segar, Brian B. Hughley, Daniel T. Bowers, Anusuya Das, Edward A. Botchwey |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Polyesters Biophysics Nanofibers Bioengineering Bone healing Mandible Article Biomaterials Paracrine signalling Mice Sphingosine medicine Animals Progenitor cell Receptor Mice Inbred BALB C Wound Healing business.industry Fingolimod Hydrochloride Regeneration (biology) Macrophages Chemotaxis Cell biology Rats Mice Inbred C57BL Receptors Lysosphingolipid medicine.anatomical_structure Mechanics of Materials Propylene Glycols Ceramics and Composites Bone marrow Lysophospholipids business Wound healing Biomedical engineering |
| Popis: | Endogenous signals originating at the site of injury are involved in the paracrine recruitment, proliferation, and differentiation of circulating progenitor and diverse inflammatory cell types. Here, we investigate a strategy to exploit endogenous cell recruitment mechanisms to regenerate injured bone by local targeting and activation of sphingosine-1-phosphate (S1P) receptors. A mandibular defect model was selected for evaluating regeneration of bone following trauma or congenital disease. The particular challenges of mandibular reconstruction are inherent in the complex anatomy and function of the bone given that the area is highly vascularized and in close proximity to muscle. Nanofibers composed of poly(DL-lactide-co-glycolide) (PLAGA) and polycaprolactone (PCL) were used to delivery FTY720, a targeted agonist of S1P receptors 1 and 3. In vitro culture of bone progenitor cells on drug-loaded constructs significantly enhanced SDF1α mediated chemotaxis of bone marrow mononuclear cells. In vivo results show that local delivery of FTY720 from composite nanofibers enhanced blood vessel ingrowth and increased recruitment of M2 alternatively activated macrophages, leading to significant osseous tissue ingrowth into critical sized defects after 12 weeks of treatment. These results demonstrate that local activation of S1P receptors is a regenerative cue resulting in recruitment of wound healing or anti-inflammatory macrophages and bone healing. Use of such small molecule therapy can provide an alternative to biological factors for the clinical treatment of critical size craniofacial defects. |
| Databáze: | OpenAIRE |
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