Advanced bioactive glue tethering Lubricin/PRG4 to promote integrated healing of avascular meniscus tears.

Meniscus injuries are extremely common with approximately one million patients undergoing surgical treatment annually in the U.S. alone, but no regenerative therapy exist. Previously, we showed that controlled applications of connective tissue growth factor (CTGF) and transforming growth factor beta 3 (TGFß3) via fibrin-based bio-glue facilitate meniscus healing by inducing recruitment and stepwise differentiation of synovial mesenchymal stem/progenitor cells. Here, we first explored the potential of genipin, a natural crosslinker, to enhance fibrin-based glue's mechanical and degradation properties. In parallel, we identified the harmful effects of lubricin on meniscus healing and investigated the mechanism of lubricin deposition on the injured meniscus surface. We found that the pre-deposition of hyaluronic acid (HA) on the torn meniscus surface mediates lubricin deposition. Then we implemented chemical modifications with heparin conjugation and CD44 on our bioactive glue to achieve strong initial bonding and integration of lubricin pre-coated meniscal tissues. Our data suggested that heparin conjugation significantly enhances lubricin-coated meniscal tissues. Similarly, CD44, exhibiting a strong binding affinity to lubricin and hyaluronic acid (HA), further improved the integrated healing of HA/lubricin pre-coated meniscus injuries. These findings may represent an important foundation for developing a translational bio-active glue guiding the regenerative healing of meniscus injuries.

The role of absolute monocyte counts in predicting severity of necrotizing enterocolitis.

OBJECTIVE: Necrotizing enterocolitis (NEC) is an inflammatory bowel disease of preterm infants marked by an absolute monocyte count (AMC) drop in peripheral blood. Our objective was to determine whether the degree of AMC drop at illness onset correlates with eventual severity of disease. STUDY DESIGN: The percentage change in AMC was retrospectively calculated for each of 29 rule-out NEC and 76 NEC cases from baseline to illness onset, and then compared across stages. RESULTS: Median AMC changes of +0.5% (p = 0.56) were found in rule-out NEC, compared with -44.5% (p < 0.0001) in Stage 2 and -81.9% (p < 0.0001) in Stage 3. An AMC change cutoff of -75% distinguishes Stages 2 and 3. CONCLUSIONS: The severity of NEC correlated with the extent of AMC change in a dose-response fashion. Percent AMC change may be a useful marker for identifying NEC at onset and prognosticating disease severity.