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Hu L.,Huazhong University of Science and Technology | Hu L.,Center for Craniofacial Regeneration | Yang G.,Center for Craniofacial Regeneration | Hagg D.,Center for Craniofacial Regeneration | And 8 more authors.
Stem Cells | Year: 2015

Adipogenesis is essential for soft tissue reconstruction following trauma or tumor resection. We demonstrate that CD31-/34+/146- cells, a subpopulation of the stromal vascular fraction (SVF) of human adipose tissue, were robustly adipogenic. Insulin growth factor-1 (IGF1) promoted a lineage bias towards CD31-/34+/146- cells at the expense of CD31-/34+/146+ cells. IGF1 was microencapsulated in poly(lactic-co-glycolic acid) scaffolds and implanted in the inguinal fat pad of C57Bl6 mice. Control-released IGF1 induced remarkable adipogenesis in vivo by recruiting endogenous cells. In comparison with the CD31-/34+/146+ cells, CD31-/34+/146- cells had a weaker Wnt/β-catenin signal. IGF1 attenuated Wnt/β-catenin signaling by activating Axin2/PPARγ pathways in SVF cells, suggesting IGF1 promotes CD31-/34+/146- bias through tuning Wnt signal. PPARγ response element (PPRE) in Axin2 promoter was crucial for Axin2 upregulation, suggesting that PPARγ transcriptionally activates Axin2. Together, these findings illustrate an Axin2/PPARγ axis in adipogenesis that is particularly attributable to a lineage bias towards CD31-/34+/146- cells, with implications in adipose regeneration. Stem Cells 2015;33:2483-2495 © 2015 AlphaMed Press.

Brown A.,598 Salk Hall | Brown A.,Center for Craniofacial Regeneration | Brown A.,360nter for Bioengineering | Zaky S.,598 Salk Hall | And 7 more authors.
Acta Biomaterialia | Year: 2015

Sixty percent of implant-supported dental prostheses require bone grafting to enhance bone quantity and quality prior to implant placement. We have developed a metallic magnesium particle/PLGA composite scaffold to overcome the limitations of currently used dental bone grafting materials. This is the first report of porous metallic magnesium/PLGA scaffolds synthesized using a solvent casting, salt leaching method. We found that incorporation of varying amounts of magnesium into the PLGA scaffolds increased the compressive strength and modulus, as well as provided a porous structure suitable for cell infiltration, as measured by mercury intrusion porosimetry. Additionally, combining basic-degrading magnesium with acidic-degrading PLGA led to an overall pH buffering effect and long-term release of magnesium over the course of a 10-week degradation assay, as measured with inductively coupled plasma-atomic emission spectroscopy. Using an indirect proliferation assay adapted from ISO 10993:5, it was found that extracts of medium from degrading magnesium/PLGA scaffolds increased bone marrow stromal cell proliferation in vitro, a phenomenon observed by other groups investigating magnesium's impact on cells. Finally, magnesium/PLGA scaffold biocompatibility was assessed in a canine socket preservation model. Micro-computed tomography and histological analysis showed the magnesium/PLGA scaffolds to be safer and more effective at preserving bone height than empty controls. Three-dimensional magnesium/PLGA composite scaffolds show promise for dental socket preservation and also, potentially, orthopedic bone regeneration. These scaffolds could decrease inflammation observed with clinically used PLGA devices, as well as enhance osteogenesis, as observed with previously studied magnesium devices. © 2014 Published by Elsevier Ltd. on behalf of Acta Materialia Inc.

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