Successful application of tissue-engineering techniques to damaged biological structures is determined by functional performance in vivo. This study evaluated the in vivo response of a tissue-engineered construct composed of a polylactic acid-alginate amalgam seeded with bone marrow-derived mesenchymal stem cells and stimulated in vitro with transforming growth factor beta for cartilage tissue engineering. Constructs were placed in cylindrical osteochondral defects in the canine femoral condyle and examined 6 weeks postoperatively by gross, histological, immunohistochemical, and biomechanical analyses. In the course of 6 weeks in vivo, the defects filled with a cartilaginous tissue regardless of whether cell-seeded (experimental) or cell-free (control) constructs were implanted; however, the quality of the tissue differed between the experimental and control defects. Cell-seeded experimental defects showed more cartilage-like matrix quality, cell distribution, and proteoglycan staining. Biomechanically, experimental and control specimens exhibited similar behavior; however, both tissues were still immature compared with normal cartilage. The evidence accumulated in this study showed a modest acceleration of the in vivo healing of cell-seeded constructs but also demonstrated a reparative response of cell-free constructs. This finding suggests that the constructs prepared from the PLA-alginate amalgam may serve as a means for host cell attachment.
Bypass grafting around a neuroma-in-continuity entails coapting a nerve graft above and below the injured segment using two sequential end-to-side repairs. The proximal repair is analogous to what has been classically described as an end-to-side repair; the axons from the intact nerve sprout into the end of a recipient nerve and travel distally. At the distal connection, however, axons in the graft must enter the side of the intact nerve and find their way to appropriate end organs. This process has not been well investigated. To examine this, a reverse end-to-side repair, suturing the distal end of the peroneal nerve to the side of a transected and repaired tibial nerve, was performed in 20 rats. A primary end-to-end repair of the tibial nerve was performed in 10 additional rats. Twelve weeks later, contraction forces of the gastrocnemius muscle were measured following proximal stimulation. Measurements were repeated following elimination of potential axonal pathways to identify which axons (peroneal or tibial) had achieved greater reinnervation. The results indicated that both groups of axons had achieved significant reinnervation. This study supports the idea that a reverse end-to-side repair can result in axonal invasion of an intact but regenerating nerve and achieve functional recovery.
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