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

Abstract

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. Conclusion 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. Level of Evidence NA Laryngoscope, 129:2189–2194, 2019

Novel Therapy for Acquired Tracheomalacia with a Tissue-Engineered Extraluminal Tracheal Splint and Autologous Mesenchymal-Derived Chondrocytes

“…Traditionally, rabbits have been used as models of tracheal airway collapse because the diameter and elasticity 27 of their trachea are similar to that of the human pediatric trachea. However, in adulthood, rabbits have almost complete tracheal rings, making this model unsuitable for our study.…”

Renal tissue engineering for regenerative medicine using polymers and hydrogels

“…It is typically produced by insect larvae in the form of cocoons at the stage of metamorphosis to become an adult. Generally, silk is recognised in tissue engineering for its biocompatibility, biodegradability and bioresorbable properties, 82,83 in addition to its processability by spin coating, 84 electrospinning 85 and cross-linking. 86 Typical silk used for tissue engineering includes silkworms from the Bombycidae and Saturniidae family, with Bombyx mori as a common species with highquality fibres.…”

Insight into Silk-Based Biomaterials: From Physicochemical Attributes to Recent Biomedical Applications

“…167,198 Resorbable SF splits for treatment of tracheomalacia (weakness/collapse of the tracheal wall) were seen to be well tolerated in acute tracheomalacia induced rabbit models. 199 Apart from medical implants, SF-based wearable resorbable microelectronics have also come into focus in recent years. 200 For instance, resorbable SF-based wireless heating devices for remotely controlled drug delivery application 201 and development of transient circuits, 202 which can be easily dissolved in aqueous conditions, hold potential for futuristic smart resorbable biomedical implants.…”

“…A few selected instances include the following: the use of micromolded and machined SF-based tympanostomy tube or ear tube for treatment of otitis media effusion (a pediatric pathological condition) showed good promise in nascent myringotomy defects in chinchillas after 8 weeks of implantation . Resorbable bone screws fabricated through macro-molding, machining for fracture fixation, and fiber-reinforced SF scaffolds for large volume defects show promising results in bone defect rabbit models. , Resorbable SF splits for treatment of tracheomalacia (weakness/collapse of the tracheal wall) were seen to be well tolerated in acute tracheomalacia induced rabbit models . Apart from medical implants, SF-based wearable resorbable microelectronics have also come into focus in recent years .…”