**3. Use of inert bridges**

The use of biomaterial bridges has been an attractive alternative for neuroregeneration. Inert bridges are temporary structures that support cell and tissue growth. These materials are biodegradable, they can foster mechanical strength, they can be fibers or porous channels, and they have the capacity of cell adhesion [21]. Hydrogels, which are biocompatible implants for repair after a TSCI, also form bridges for regeneration as well as preventing fibroglial scar formation, thus promoting a permissive environment for regeneration. Third-dimensional nanofibers have also been designed, which provide better cell adhesion and promote migration, cell proliferation, and differentiation [21].

These bridges can be made of biological materials such as collagen or fibronectin; or of natural polymers such as alignate, agarose, or chitosan; or they can also be composed of synthetic polymers such as polyhydroxy-α, poly-2-hydroxyethylmethacrylate, or polyethylene glycol [22, 23].

It has been shown that these materials in TSCI models (contusions, transection, or hemisections) can favor and direct axonal growth, since they act as bridges [24, 25]. They have also been found to be compatible when used in combination with other treatments such as cell or trophic factors, promoting a permissive environment for this axonal growth [26–28]. Furthermore, it has been observed that they help the adhesion of oligodendrocytes, or Schwann cells, thus favoring remyelination of damaged axons [29].

## **4. Cellular therapy**

The term cellular therapy (CT) refers to any type of strategy that uses cells as a therapeutic agent. Neural transplantation has been used to repair injured SC in both acute and chronic phases. The use of cell transplants has been a positive alternative for axonal regeneration. Different cell types have been used during these transplants such as: Schwann cells, olfactory ensheathing glia (OEG) cells, embryonic stem cells, hematopoietic cells, neural stem cells and bone marrow stromal cells (BMSCs) [30].

#### **4.1 Schwann cells**

In the PNS, unlike the CNS, regeneration is efficient due to the presence of Schwann cells (Cs). Cs have been used to perform transplants in different animal models since they are capable of: engulfing cellular debris, producing trophic factors necessary for the survival of the neuron (especially brain-derived neurotrophic factor (BDNF) and neurotrophin 4/5 (NT4/5)), secreting cell matrices of inhibitory molecules that help axonal regrowth, and producing myelin layers to envelop the naked axons and increase the impulse speed of nerve cells to improve their functioning [31]. In rodent models, Cs implants have been shown to foster remyelination, thus improving motor functions in contusion and complete section injuries [32, 33]. Combination with other materials has also been shown to help guide axonal regrowth after a TSCI [34, 35].
