Evaluation of a Tissue Engineered Material for Flexor Tendon Grafting in a Rabbit Model
ABSTRACT
The ideal tendon repair material combines availability, minimal donor-site morbidity and operative time, with reliable healing and satisfactory postoperative function. A commercially available tissue-engineered porcine small-intestinal submucosa may be a suitable human flexor tendon substitute. Flexor tendon grafting using small-intestinal submucosa was compared to tendon autografting in the rabbit flexor zone II equivalent.
A 1-cm segment of the flexor digitorum profundus tendon was excised from the zone II forepaw middle digit in 40 male New Zealand White rabbits. Rabbits were randomized to tendon deficit repair with reversed autograft or small-intestinal submucosa. Both materials were passed beneath the A2 and A4 pulleys. Forepaws were statically splinted in wrist and metacarpophalangeal joint flexion for 3 weeks followed by unrestricted motion. Animals were sacrificed at 7, 14, 28, and 56 days. Specimens were analyzed for hydroxyproline content and tensile strength. Hematoxylin-eosin and Movat-stained sections of the central graft and distal repair site were semiquantitatively scored by a blinded pathologist for total cellularity, inflammatory cell content, foreign-body reaction, vascularity, elastin, mature collagen content, and new collagen deposition.
Net autograft collagen degradation reduced hydroxyproline content to 80% by 2 weeks. Collagen deposition in the small-intestinal submucosa was evident microscopically by 1 week. Hydroxyproline content in the small-intestinal submucosa was equivalent to autograft by 2 weeks. New collagen deposition was slower in autograft than small-intestinal submucosa (Movat). Greater increases in total and inflammatory cellularity occurred more rapidly in small-intestinal submucosa than in autograft during the initial 4 weeks. However, a foreign-body reaction did not occur until 4 weeks postoperatively. Neovascularization of small-intestinal submucosa occurred more quickly than autograft and is markedly greater at 1, 2, and 4 weeks (P=.076-week 2). Although hydroxyproline content remained less than autograft at 4 weeks, small-intestinal submucosa had better intrinsic tensile strength (suture removed) at 4 weeks than either autograft or suture material (P=.059). Tendon excursion was poor in both groups. Transforming growth factor-ß and TGF-ß receptor staining will be discussed.
Small-intestinal submucosa is a promising tissue-engineered material for flexor tendon grafting. Early neovascularization and autogenous collagen deposition offsets initial collagen degradation. Small-intestinal submucosa intrinsic repair strength exceeds that of autograft and suture strength by 4 weeks. Inflammatory adhesions to small-intestinal submucosa may not affect humans performing early active motion. Evaluation at 8 weeks will determine whether a foreign body reaction to small-intestinal submucosa impairs healing at 8 weeks, and the feasibility of proceeding with tendon grafting with small-intestinal submucosa in humans.