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Topical application of laminin-332 to diabetic mouse wounds

      Summary

      Background

      Keratinocyte migration is essential for wound healing and diabetic wound keratinocytes migrate poorly. Keratinocyte migration and anchorage appears to be mediated by laminin-332 (LM-332). Impaired diabetic wound healing may be due to defective LM-332 mediated keratinocyte migration.

      Objective

      To evaluate LM-332 expression in diabetic (db/db) and control (db/−) mice and to test LM-332 wound healing effects when applied to mouse wounds.

      Methods

      LM-332 expression in mouse wounds was evaluated using immunohistochemistry. LM-332 wound healing effects were evaluated by directly applying soluble LM-332, a LM-332 biomaterial, or a control to mouse wounds. Percent wound closure and histology score, based on healing extent, were measured.

      Results

      Precursor LM-332 expression was markedly reduced in db/db when compared to db/− mice. In vitro, soluble LM-332 and LM-332 biomaterial demonstrated significant keratinocyte adhesion. In vivo, soluble LM-332 treated wounds had the highest histology score, but significant differences were not found between wound treatments (p > 0.05). No differences in percentage wound closure between treatment and control wounds were found (p > 0.05).

      Conclusion

      The db/db wounds express less precursor LM-332 when compared to db/−. However, LM-332 application did not improve db/db wound healing. LM-332 purified from keratinocytes was primarily physiologically cleaved LM-332 and may not regulate keratinocyte migration. Application of precursor LM-332 rather than cleaved LM-332 may be necessary to improve wound healing, but this isoform is not currently available in quantities sufficient for testing.

      Keywords

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