Plastic Surgery Research Council
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TISSUE ENGINEERED TENDON-BONE COMPOSITE GRAFTS FOR RECONSTRUCTION OF THE TENDON-BONE INTERFACE - AN EXPERIMENTAL STUDY IN RAT
Presenter: Simon Farnebo, MD PhD
Co-Authors: Woon CY; Bronstein JA; Schmitt T; Lindsey DP; Chang J
Stanford University

Restoration of biomechanical strength following surgical reconstruction of tendon insertion tears are challenging because these injuries typically heal as fibrous scars. We hypothesize that injuries at the tendon-bone interface (TBI), such as digital flexor Zone I injuries, would benefit from reconstruction with decellularized grafts. Tendon-bone composite grafts were harvested from rats. Grafts subjected to physicochemical decellularization, including targeted ultrasonication were compared histologically and biomechanically with untreated grafts. Decellularized and untreated grafts were then compared in a new in vivo model. Sprague Dawley rats underwent Wistar TBI allograft reconstruction using a pair-matched design. The rats were sacrificed at 2 or 4 weeks and tested biomechanically. Also, B-cell and macrophage infiltration was determined using immunohistochemistry. Finally, the decellularized grafts were seeded with adipoderived stem cells transfected with a GFP and luciferin construct. Bioluminescence of seeded grafts was evaluated in vitro, and continuously up to 14 days after in vivo reconstruction. Physicochemical decellularization resulted in almost complete reduction of visible cells and nucleic acid material, with preserved structure. Biomechanical comparison of decellularized and untreated grafts revealed no difference in failure load (706 N vs 7618, p=0.24). There was improved failure load in decellularized grafts compared to untreated grafts at both 2 weeks (33.67.5N vs 24.09.8N, p=0.044) and 4 weeks (46.57.5N vs 22.77.3N, p=0.042) after in vivo reconstruction. A persistent increase in B-cell and macrophage infiltration was observed in both in the capsule surrounding the TBI, and the tendon substance, in the untreated compared with the decellularized group. Ex vivo seeded grafts that were re-implanted showed cell survival over a 2-week period. Histology demonstrated successful GFP+ cell revitalization of all component tissues in the composite construct. In the future, decellularized tissue grafts reseeded with stem cells may constitute a treatment option for reconstruction of TBI injuries.


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