Effects of lubricant and autologous bone marrow stromal cell augmentation on immobilized flexor tendon repairs

Abstract

The purpose of the study was to test a novel treatment that carbodiimide-derivatized-hyaluronic acid-lubricin (cd-HA-lubricin) combined cell-based therapy in an immobilized flexor tendon repair in a canine model. Seventy-eight flexor tendons from 39 dogs were transected. One tendon was treated with cd-HA-lubricin plus an interpositional graft of 8 × 10(5) BMSCs and GDF-5. The other tendon was repaired without treatment. After 21 day of immobilization, 19 dogs were sacrificed; the remaining 20 dogs underwent a 21-day rehabilitation protocol before euthanasia. The work of flexion, tendon gliding resistance, and adhesion score in treated tendons were significantly less than the untreated tendons (p < 0.05). The failure strength of the untreated tendons was higher than the treated tendons at 21 and 42 days (p < 0.05). However, there is no significant difference in stiffness between two groups at day 42. Histologic analysis of treated tendons showed a smooth surface and viable transplanted cells 42 days after the repair, whereas untreated tendons showed severe adhesion formation around the repair site. The combination of lubricant and cell treatment resulted in significantly improved digit function, reduced adhesion formation. This novel treatment can address the unmet needs of patients who are unable to commence an early mobilization protocol after flexor tendon repair.

Keywords: bone marrow stromal cells; flexor tendon; hyaluronic acid; immobilization; lubricin; tendon repair.

Figure 1

Gross observation after dissection of the repaired tendon. Treated repairs showed smooth tendon surfaces without adhesion at days 21 (A) and 42 (C). Untreated repairs showed adhesions (arrows) around the repair site at days 21 (B) and 42 (D).

Figure 2

Normalized work of flexion (A) and repaired tendon gliding resistance (B) studies showed improved digit function and gliding ability in treated tendons. Groups with different letters indicate a significant difference (p < 0.05).

Figure 3

Maximum failure strength of repaired tendons was lower in treated tendons versus untreated tendons (A); this difference might be attributable to excessive adhesions in untreated tendons. However, stiffness was similar between treated and untreated repaired tendons on postoperative day 42 (B). Groups with different letters indicate a significant difference (p < 0.05), for example, a < b < c < d.

Figure 4

Histology (hematoxylin and eosin) showed a viable cell-seeded patch on postoperative day 21 at the lacerated tendon ends (A and B), but acellular features at the repair site were noted in untreated tendons (C and D). After 42 days, lacerated tendon ends were fused in treated and untreated tendons (E and G). Treated tendons had a smooth surface at the repair site (E and F), but untreated tendons had abundant adhesions at the repair site surface (G and H).

Figure 5

Transplanted cells labeled with Vybrant DiI cell tracking solution (red fluorescence) were observed at the repair site of the treated tendons (A, 21 days; C, 42 days). Untreated tendons were negative for fluorescence under confocal microcopy (B and D).