No abstract

In the past decade, substantial strides have been taken toward the use of human adipose-derived stromal/stem cells (hASC) in the regeneration of bone. Since the discovery of the hASC osteogenic potential, many models have combined hASC with biodegradable scaffold materials. In general, rats and immunodeficient (nude) mice models for nonweight bearing bone formation have led the way to assess hASC osteogenic potential in vivo. The goal of this review is to present an overview of the recent literature describing hASC osteogenesis in conjunction with three-dimensional scaffolds for bone regeneration.

In this study, three different akermanite:poly-ϵ-caprolactone (PCL) composite scaffolds (wt%: 75:25, 50:50, 25:75) were characterized in terms of structure, compression strength, degradation rate and in vitro biocompatibility to human adipose-derived stem cells (hASC). Pure ceramic scaffolds [CellCeram™, custom-made, 40:60 wt%; β-tricalcium phosphate (β-TCP):hydroxyapatite (HA); and akermanite] and PCL scaffolds served as experimental controls. Compared to ceramic scaffolds, the authors hypothesized that optimal akermanite:PCL composites would have improved compression strength and comparable biocompatibility to hASC. Electron microscopy analysis revealed that PCL-containing scaffolds had the highest porosity but CellCeram™ had the greatest pore size. In general, compression strength in PCL-containing scaffolds was greater than in ceramic scaffolds. PCL-containing scaffolds were also more stable in culture than ceramic scaffolds. Nonetheless, mass losses after 21 days were observed in all scaffold types. Reduced hASC metabolic activity and increased cell detachment were observed after acute exposure to akermanite:PCL extracts (wt%: 75:25, 50:50). Among the PCL-containing scaffolds, hASC cultured for 21 days on akermanite:PCL (wt%: 75:25) discs displayed the highest viability, increased expression of osteogenic markers (alkaline phosphatase and osteocalcin) and lowest IL-6 expression. Together, the results indicate that akermanite:PCL composites may have appropriate mechanical and biocompatibility properties for use as bone tissue scaffolds.

Failure to resolve inflammation underlies many prevalent pathologies. Recent insights have identified lipid mediators, typified by lipoxins (LXs), as drivers of inflammation resolution, suggesting potential therapeutic benefit. We report the asymmetric preparation of novel quinoxaline-containing synthetic-LXA 4 -mimetics (QNX-sLXms). Eight novel compounds were screened for their impact on inflammatory responses. Structure–activity relationship (SAR) studies showed that ( R )- 6 (also referred to as AT-02-CT) was the most efficacious and potent anti-inflammatory compound of those tested. ( R )- 6 significantly attenuated lipopolysaccharide (LPS)- and tumor-necrosis-factor-α (TNF-α)-induced NF-κB activity in monocytes and vascular smooth muscle cells. The molecular target of ( R )- 6 was investigated. ( R )- 6 activated the endogenous LX receptor formyl peptide receptor 2 (ALX/FPR2). The anti-inflammatory properties of ( R )- 6 were further investigated in vivo in murine models of acute inflammation. Consistent with in vitro observations, ( R )- 6 attenuated inflammatory responses. These results support the therapeutic potential of the lead QNX-sLXm ( R )- 6 in the context of novel inflammatory regulators.