Tiam Mana Saffari

174 CHAPTER 8 Table 2 – Overview of delivery methods of stem cells, showing its efficiency, advantages, and disadvantages. 17,51,53 Methods Efficiency Advantage Limitations Intravenous injection 100% - Does not induce nerve damage and cell-leakage - Focusses on the trophic function of stem cells - Entrapment stem cells in capillaries - The desired amount at the recipient site may not suffice - Reduction stem cell viability after needle passage due to pressure build-up Intramuscular injection 100% - Does not induce nerve damage and cell-leakage - Significantly improves functional recovery and neuro-conduction velocity compared to intravenous injection - Enhances nerve regeneration - Reduction stem cell viability after needle passage due to pressure build-up, low number of stem cells at nerve regeneration site Dynamic seeding on nerve grafts or conduits 89.2% - Does not harm stem cells or nerve infrastructure - More successful than static seeding, uniform distribution of adhered stem cells - Upregulation neurotrophic factors - Very promising method - Stem cells do not migrate from the delivery site - Can only be used when the nerve gap is bridged with a nerve graft or conduit Intra-neural microinjection 10-40% - Delivers a high quantity of cells directly to the site of the inner and middle nerve zones - Traumatic to stem cells as well as intra-neural architecture - Unpredictable cell distribution, reduction stem cell viability after needle passage due to pressure build-up - Leakage cells - May obstruct axonal ingrowth Microinjection around nerve 10-40% - Does not induce nerve damage and cell-leakage - Outcomes comparable to intra-neural microinjection - Reduction stem cell viability after needle passage due to pressure build-up Cell encapsulation Unknown - Overcomes side effects of transplantation (e.g. teratoma formation, tumors) - Prevents in vivo migration of cells - Enhances the formation of multicellular aggregates - A high volume of micro-particles needed to reach a beneficial number of cell release Hydrogel Unknown - Similarity to extracellular matrix - Can be processed under mild conditions - Minimally invasive delivery - Degradation can be designed to coincide with angiogenesis and revascularization - Potentially clinical translatable - Research is still in the early stage - Degradation hydrogel may affect stem cell survivability 3-D printing Unknown - Includes the personalized complex features of the nerve structures - Research is still in the early stages - Technical challenges to realize the formation of the desired nerve structure