Tiam Mana Saffari

176 CHAPTER 8 vascularity in nerve regeneration, which creates an opportunity for elucidating its synergistic pathways in future research. Future applications Future applications integrating stem cell-based therapies with the promotion of angiogenesis are needed to enhance nerve regeneration through multiple pathways. Feasibility with respect to cost and time efficiency is needed for translation to clinical practice. Current research developing future applications includes prevascularized stem cell nerve conduits, three-dimensional printing, and hydrogel scaffolding 29,96,97 . Fan et al. have developed a novel prevascularized nerve conduit based on a MSC sheet for treating spinal cord injuries, resulting in enhanced nerve regeneration and revascularization 96 . Other novel research has focused on three-dimensional printing in order to fabricate a nerve guidance conduit with stem cells that reproduces the complex nerve features of a patient’s long nerve defect, such as branching nerve networks and intrinsic chemical mechanisms that steer regenerating motor and sensory axons along correct anatomical pathways. Three-dimensional printing may provide the desired personalized dimensions and structures for nerve regeneration and cell organization 97 . Another novel future application focusses on promising stem cell delivery methods, which are still in early stages of research, such as stem cell encapsulation delivered in a hydrogel scaffold 29,98 . Hydrogels constructed of natural biomaterials, including collagen and fibrin, as well as synthetic biomaterials such as poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG), may act as carriers for delivery of stem cells or growth factors. The use of hydrogel as a scaffold is attractive due to its high water content mimicking an extracellular matrix as well as its ease of delivery. Hydrogel degradation can be designed to respond to tissue proteases and to deliver stem cells or other growth factors in a timely manner to coincide with the processes of angiogenesis. In vascular tissue engineering, PLGA hydrogels have been designed to ensure a controlled release of angiogenic factors such as VEGF for an extended release time. Basic criteria for the use of hydrogel include effective cell adhesion to the gel matrix, sufficient stem cell survival in the hydrogel, safety for the micro-environment, and mechanical stability 29,99 . The use of prefabricated conduits or encapsulated cells