Preclinical assessment of resorbable silk splints for the treatment of pediatric tracheomalacia.

OBJECTIVE

Tracheomalacia is characterized by weakness of the tracheal wall resulting in dynamic airway collapse during respiration; severe cases often require surgical intervention. Off-label external splinting with degradable implants has been reported in humans; however, there remains a need to develop splints with tunable mechanical properties and degradation profiles for the pediatric population. The objective of this pilot study is to assess the safety and efficacy of silk fibroin-based splints in a clinically relevant preclinical model of tracheomalacia.

METHODS

Silk splints were evaluated in a surgically induced model of severe tracheomalacia in N = 3 New Zealand white rabbits for 17, 24, and 31 days. An image-based assay was developed to quantify the dynamic change in airway area during spontaneous respiration, and histopathology was used to study the surrounding tissue response.

RESULTS

The average change in area in the native trachea was 23% during spontaneous respiration; surgically induced tracheomalacia resulted in a significant increase to 86% (P < 0.001). The average change in airway area after splint placement was reduced at all terminal time points (17, 24, and 31 days postimplantation), indicating a clinical improvement, and was not statistically different than the native trachea. Histopathology showed a localized inflammatory reaction characterized by neutrophils, eosinophils, and mononuclear cells, with early signs suggestive of fibrosis at the splint and tissue interface.

CONCLUSIONS

This pilot study indicates that silk fibroin splints are well tolerated and efficacious in a rabbit model of severe tracheomalacia, with marked reduction in airway collapse following implantation and good tolerability over the studied time course.

METHODS

NA. Laryngoscope, 2018.