Table 2.

Studies Using Olfactory Ensheathing Cells–Seeded Scaffolds.

Study	Cell types	Scaffold type	Outcome	References
Partial recovery with dorsal root injury in rats Injury model: Rat unilateral four root dorsal transection injury (C6, C7, C8, and T1 region)	Human olfactory bulb OECs	3D collagen scaffold	4.8 mg/ml collagen with 1 × 106 cells gave an optimal cellular network of OECs. Microglial activation in the deep dorsal horn of cervical C7 and C8 level or axonal loss in C3 level was observed in the responder rats; 30% errors observed in climbing performance of control rats compared with rats with OEC transplants	Collins et al. 122
OEC collagen grafts do not improve spinal trauma-induced motor deficits. Injury model: Rat 2 mm long unilateral low—thoracic hemisection cavities (T13 region)	Rat olfactory bulb OECs	2 mm long cylindrical collagen scaffolds with diameter of 2 mm	Implantation of collagen scaffold seeded with OECs did not improve or worsen motor outcomes and allodynia following thoracic SCI hemisection in rats	Deumens et al. 123
Phenotypic study of rat OECs on 3D collagen scaffolds	Rat olfactory bulb–derived OECs	The average pore size of the 3D collagen scaffold was 20–100 µm in diameter	3D collagen scaffold is biocompatible with OECs and scaffolds yielded 67% more OECs compared with monolayer culture. Also, spindle-like bipolar morphology of OEC was retained on 3D collagen scaffolds	Wang et al. 124
In vitro biocompatibility of OECs with biomimetic silk scaffold	Rat olfactory bulb OECs	Bombyx mori porous silk scaffold	Water-rinsed silk fibroin scaffolds were biocompatible with OECs, favored cell proliferation and secretion of neurotrophic factors	Wentao et al. 125
Optimal diameter of scaffold helps in guiding growth and migration of OECs	Rat olfactory bulb OECs	SFS	300 nM SFS is biocompatible for culture and unidirectional migration of OECs	Shen et al. 126
Microencapsulation of transplanted OECs reduce pain post sciatic nerve injury L4–L5 dorsal root ganglia C chronic sciatic nerve compression injury	Rat olfactory bulb OECs	Cell suspension was mixed 1:1 with 1.5% alginic acid	Purinergic receptor P2X2/3 expression is elevated in chronic constriction injury (CCI) models. Microencapsulation of OECs reduced pain after sciatic nerve injury	Zhao et al. 127
Potential biomaterials functioning as cell carriers for neuro transplantation	Rat olfactory bulb OECs	2% alginate, alginate-0.025% fibronectin hydrogel 500–800 µm alginate and matrigel preparation	Alginate-fibronectin increased proliferation of OECs but significantly lower than with matrigel. Neurite outgrowth of OECs was increased in alginate-fibronectin hydrogel compared with alginate alone	Novikova et al. 128
Neuroregenerative properties of OECs in multi-layered conductive nanofibrous conduits Injury model: 8 mm transected sciatic nerve in rats	Rat olfactory bulb OECs	Single-walled carbon nanotube/poly (L-lactic acid) (SWCNT/PLLA) scaffolds	OEC-seeded nerve conduits transplanted to the transected rat sciatic nerve improved axonal growth and peripheral nerve regeneration	Kabiri et al. 129
Long-distance axon regrowth in presence of OECs, olfactory nerve fibroblasts and biomaterials Injury model: Rat 2 mm long dorsal hemisected (T11/T12 region) SCI model	Rat olfactory bulb OECs/ONF	Poly(d, l)-lactide matrices	Lack of OEC/ONF migration from the rostral/caudal site of injection to injury site and poor cell survival on biomatrices due to low seeding numbers of OEC/ONF and incompatibility of biomatrices. Modest locomotory function seen in swing speed, stride length in hind limbs, and axonal regrowth after OEC/ONF transplantation	Deumens et al. 130
Enhanced neural regeneration with OECs in PLGA scaffolds Injury model: Rat 2 mm wide complete transected (T9–T10 region) SCI model	Rat olfactory bulb OECs	PLGA pore size 300–500 µM	Enhanced locomotor function, axon myelination, neuronal protection, and decreased astrogliosis post SCI in PLGA and OEC combination compared with PLGA or untreated groups	Wang et al. 131
Directionality and bipolarity of OECs on electrospun nanofibers	Rat OECs	PLGA	Nano composite electrospinning fibers of 237 nm diameter favored bipolarity and unidirectional migration of OECs	Kueh et al. 132
PLGA with OECs for bridging sciatic nerve defects in rats Injury model: 7 mm sciatic was resected to 10 mm nerve defect	Rat olfactory bulb OECs	100 µM diameter PLGA (with 85:15 carboxyl end)	A combination of PLGA and OECs can improve the functional and structural outcome in defective sciatic nerve but the sciatic functional index cannot be recovered in more serious injuries	Li et al. 133
OECs combined with chitosan decreased neuropathic pain. Injury model: Chronic sciatic nerve compression injury in rats	Rat olfactory bulb OECs	Chitosan	OEC-seeded chitosan scaffolds can inhibit Purinergic receptor (P2X7R) overexpression and reduce neuropathic pain	Zhang et al. 134
Electrical stimulation of OECs using conductive polymers	Rat olfactory bulb OECs	0.4 mm Polypyrrole/chitosan polymers	Polypyrrole/chitosan membranes supported cell adhesion and proliferation even without electrical stimulation. Stimulation increased secretion of neurotrophic factors	Qi et al. 135
3D printed polycaprolactone/polypyrrole conducting scaffolds aid neurite outgrowth	Human OE-MSCs	PCL/polypyrrole (PPy) conducting scaffolds	OE-MSCs on scaffolds showed increased differentiation to Schwann-like cells, increased secretion of NGF and BDNF, and increased neurite outgrowth but conductivity of scaffold had no effect on cell attachment, proliferation, viability, and distribution	Entezari et al. 136
Interactions between Schwann cells (SCs) and OECs with starch/polycaprolactone scaffold	Rat olfactory bulb OECs and sciatic nerve Schwann cells	SPCL	OECs and SCs are biocompatible with SPCL. Improved growth, proliferation, and migration of cells was observed in long-term culture	Silva et al. 137
Comparison of scaffolds for migration and growth of glial cells	Rat OECs	PCL and C/PCL	C/PCL biomaterial made scaffold is better suited for cell proliferation, migration, and neurite outgrowth	Schnell et al. 138
Characterization of OECs cultured on polyurethane/polylactide scaffold	Rat olfactory bulb OECs	PU/PLDL scaffold	Different ratio of PU to PLDL did not alter phenotype of OECs but proliferation rate depended upon equal ratio of polymers	Grzesiak et al. 139
BioPEGylation of PHB-polyethylene glycol (PHB-b-DEG) hybrid polymers promotes healthy nerve cell and migration	OECs	Polyhydroxybutyrate-polyethylene glycol	bioPEGylated PHB supported OEC migration, promoted cell proliferation and attachment. No cytotoxicity response in OECs	Chan et al. 140
Compatibility of OECs with a self-assembling peptide scaffold	Rat olfactory bulb OECs	A new peptide hydrogel scaffold GRGDSPmx	On the new scaffold, OEC proliferation was increased, cells showed less apoptosis and maintained spindle-shaped morphology	Zhang et al. 141
Albumin scaffold seeded with adipose-derived stem cells and OECs for spinal cord injury repair	Adipose-derived stem cells and rat OECs	Serum-derived albumin scaffold	Rats treated with cell-seeded scaffolds showed improved locomotor skills and presence of cells expressing neuronal markers at injury site	Ferrero-Gutierrez et al. 142
Improved locomotor behavior in rats after delayed cell transplantation into transected spinal cord Injury model: Rat rostrocaudally 3–4 mm complete transected (T9–T11 region) SCI model	Rat olfactory lamina propria	Three to five 1 mm2 lamina propria pieces/Gelfoam	Olfactory lamina propria grafts result in gradual improvement in locomotor recovery and axonal regeneration	Lu et al. 143

OEC: olfactory ensheathing cell; SFS: silk fibroin scaffolds; SCI: spinal cord injury; ONF: olfactory nerve fibroblasts; PLGA: poly (lactic-co-glycolic-acid); OE-MSC: olfactory ecto–mesenchymal stem cell; PCL: poly-ε-caprolactone; NGF: nerve growth factor; BDNF: brain-derived neurotrophic factor; SPCL: starch-based polycaprolactone scaffold; C/PCL: collagen/Poly-ε-caprolactone; PU/PLDL: polyurethane/polylactide; PHB: polyhydroxybutyrate.