Tiam Mana Saffari

240 CHAPTER 11 Collagens are abundantly present in the ECM of peripheral nerves. Of the 29 collagen types, type I and III, specifically, are believed to provide mechanical support for axonal growth and regeneration after peripheral nerve injury 38,39 . In this chapter, a significant increase was found in gene expression profiles of collagen type I and III in nerve allografts wrapped around with the SIEF flap. These SIEF samples also confirmed increased angiogenesis, using various angiogenic markers i.e. Cd34, Pecam1/Cd31, Vegfa and Mmp2. Furthermore, using flowcytometry, peripheral T cells were evaluated in the blood samples of rats. At one week postoperatively, T helper population (CD4) was significantly increased in SIEF rats, compared to baseline, untreated rats. These data support the hypothesis that an adipofascial flap plays a role in suppressing nerve fibrosis after injury, by providing both an immune tolerant paracrine environment and increasing angiogenesis to the nerve allograft. Achieving a reduction of fibrotic tissue formation is a desired aim and hallmark of improved nerve regeneration. The in vivo setting of Chapter 6 brings along both advantages as disadvantages that need to be addressed. First, this study lacks gene expression profile evaluation over time. Gene expression varies significantly over time and following these profiles over a time course may provide more information. Due to experimental logistics, costs of surgery and animal maintenance, obtaining longitudinal gene expression values remains more feasible in vitro 40,41 . Second, data on baseline expression in healthy peripheral nerves is scarce, making it difficult to understand causal relationships in gene regulation pathways. On the other hand, the in vivo setting allowed for environmental cues, such as growth factors and supporting cells, reflecting changes in the context of the ECM environment. These cues influence the proliferation and differentiation of immune cells and stem cells, reflecting a physiologically realistic context 42 . In Chapter 7 , the aimwas to investigate the impact of angiogenesis on motor recovery. While various outcomemeasurements are available to assess motor recovery, isometric tetanic force (ITF) has remained a reliable technique in determining the degree of motor recovery of a reinnervated muscle as a direct measure of reinnervation 43 . In this chapter, it was found that augmentation of decellularized nerve allografts with angiogenesis resulted in enhanced early motor recovery, comparable to autografts. The contributing factors hypothesized to be leading to this result are twofold and answer