Successful Incorporation of Tissue-Engineered Porcine Small-Intestinal Submucosa as Substitute Flexor Tendon Graft Is Mediated by Elevated TGF-β1 Expression in the Rabbit

Purpose: Ideal tendon repair materials combine minimal donor-site morbidity and ready availability with excellent healing and postoperative function. Bioengineered porcine small-intestinal submucosa (SIS) was compared with tendon autografts as a potential human flexor tendon graft substitute. Methods: Rabbit zone II flexor digitorum profundus segments were excised in 40 rabbits. Randomized tendon repair consisted of either interposition reversed autograft or SIS, passed beneath the A2 and A4 pulleys. Forepaws were statically splinted for 3 weeks followed by unrestricted motion. Animals were killed at 7, 14, 28, and 56 days. Specimens were analyzed for hydroxyproline content (absorption spectroscopy) and tensile strength. Hematoxylin-eosin and Movat-stained sections of the central graft and distal repair site were semiquantitatively scored for total cellularity, inflammatory cell content, foreign-body reaction, vascularity, mature collagen content, and new collagen deposition. Transforming growth factor-β (TGF-β1) and TGF-β1 receptor immunostaining was performed. Results: At week 1, SIS hydroxyproline content was significantly reduced compared with autograft hydroxyproline content. However, week 2 SIS hydroxyproline content increased to equivalent values. Collagen deposition was evident in SIS by week 1 but negligible in autograft. More rapid total and inflammatory cell increases occurred in SIS by 4 weeks. A stronger early inflammatory reaction also occurred. More rapid SIS neovascularization occurred despite a greater foreign-body reaction. Small-intestinal submucosa vascularity was markedly greater at weeks 1 and 2 and equivalent thereafter. At week 4, SIS intrinsic tensile strength (suture removed) exceeded that of both autograft and suture material. Preoperative TGF-β1 immunostaining in SIS was less than that of autograft but greater during weeks 2 and 4. Conclusions: Earlier neovascularization, increased TGF-β1 levels, and increased collagen deposition, along with greater intrinsic repair strength relative to both autograft and suture strength at week 4, make SIS a promising flexor tendon graft substitute. Future studies examining tendon excursion are planned.