Hypertrophic scars (HSs) and
keloids are histologically characterized by excessive extracellular matrix (ECM) deposition. ECM deposition depends on the balance between
matrix metalloproteinases (
MMPs) and tissue inhibitors of
metalloproteases (TIMPs).
TIMP-1 has been linked to ECM degradation and is therefore a promising therapeutic strategy. In this study, we generated super
carbonate apatite (sCA) nanoparticle-encapsulated
TIMP-1 small interfering RNA (
siRNA) (siTIMP1) preparations and examined the effect of local
injections on mouse HSs and on ex vivo-cultured
keloids. The sCA-siTIMP1
injections significantly reduced
scar formation,
scar cross-sectional areas,
collagen densities, and
collagen types I and III levels in the lesions. None of the mice died or exhibited abnormal endpoints.
Apatite accumulation was not detected in the other organs. In an ex vivo
keloid tissue culture system, sCA-siTIMP1
injections reduced the thickness and complexity of
collagen bundles. Our results showed that topical sCA-siTIMP1
injections during mechanical stress-induced HS development reduced
scar size. When
keloids were injected three times with sCA-siTIMP1 during 6 days, keloidal
collagen levels decreased substantially. Accordingly, sCA-
siRNA delivery may be an effective approach for
keloid treatment, and further investigations are needed to enable its practical use.