Barbizan et al. (2014) [16] |
To investigate two delivery strategies of mononuclear cells (MC), comparing the local injection to the spinal cord with the possibility of mixing MC with HFB on the interface of the CNS/PNS. |
Forty female adult Lewis rats divided into: G1: avulsion only; G2: reimplantation with HFB; G3: root repair with HFB and MC; G4: root repair with HFB and injected MCs. |
HFB enhanced cell therapy effects resulting in greater survival of spinal motoneurons up to four weeks post-surgery. MC added to the HFB increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. The motor recovery was similar to cell-treated groups. |
The use of HFB as a scaffold for the MC delivery approach gave the best and most long-lasting results. MC therapy was neuroprotective by increasing levels of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF). |
Buchaim et al. (2015) [17] |
To assess whether HFB permits the collateral repair of axons originating from a vagus nerve to the interior of a sural nerve graft and whether low-level laser therapy (LLLT) assists in the regeneration process. |
Thirty-two adult male Wistar rats divided into: G1: intact sural nerve; G2: the ends of the sural nerve graft were coapted to the vagus nerve using HFB; G3: same procedures as G2 + LLLT. |
The vagus nerve demonstrated collateral regeneration of axons to the interior of the autologous graft in all groups. G3 was similar to G1 concerning the area and thickness of the myelin sheath. |
HFB + LLLT makes axonal regeneration feasible and is an efficient method to recover injured peripheral nerves, as well as improve myelination. |
Cartarozzi et al. (2015) [18] |
To investigate the effectiveness of mesenchymal stem cells (MSCs) associated with HFB for the peripheral regenerative process after nerve tubulization. |
One hundred adult Lewis rats divided into G1: empty tube; G2: tube filled with HFB; G3: tube filled with HFB and grafted with MSCs. |
G3 had a greater value for myelinated axon counting, more compact fibers, and a tendency to increase the thickness of the myelin sheath; with better motor function. |
MSCs + HFB treatment was effective in improving nerve regeneration, as it positively modulated Schwann Cells reactivity. |
Buchaim et al. (2016) [19] |
To assess the impact of LLLT on the repair of the buccal branch of the facial nerve using two surgical methods: end-to-end epineural suturing and coaptation with HFB. |
Forty adults male Wistar rats divided into: G1: suture; G2: HFB; G3: suture + HFB; G4: suture + LLLT; G5: suture + HFB + LLLT. |
Axonal sprouting and morphology were similar among the experimental groups. G5 showed the closest results to the G1, in all measured variables, except in the axon area. |
HFB allowed the coaptation of the stumps without trauma to the nerve fibers. |
Rosso et al. (2017) [20] |
To assess the impact of LLLT on facial nerve injuries repaired with the end-to-side method or coaptation with HFB. |
Thirty-two adults male Wistar rats divided into G1: control; G2: suture; G3: HFB; G4: suture + LLLT; G5: suture + HFB + LLLT. |
G4 and G5 groups showed higher mean values for histomorphometry and functional recovery variables. |
The functional recovery of whisker movement occurred more rapidly in G4 and G5, with results closer to G1. LLLT expedited morphological and functional nerve repair in both techniques. |
Spejo et al. (2018) [21] |
To evaluate whether the combination of MSCs and HFB enhances the regeneration of the spinal cord following intramedullary axotomy (IA) |
Eighty-eight adult female Lewis rats underwent a unilateral ventral funiculus incision at the L4, L5, and L6 spinal levels. The animals were divided into: G1: IA, G2; IA + vehicle; G3: IA + HFB; G4: IA + MSC; G5: IA + HFB + MSC. |
MSC therapy: increased neuronal survival and functional recovery, reduced astrogliosis, and preserved spinal circuits. HFB promoted: early macrophage recruitment and expression of proinflammatory cytokines. |
MSC therapy provides neuroprotection and, when combined with HFB, shifts the immune response towards the proinflammatory profile. |
Mozafari et al. (2018) [22] |
To determine whether human embryonic stem cells (hESC), either independently or in conjunction with HFBs, could aid in regeneration in a mouse model of sciatic nerve damage. |
Forty-eight C57BL/6 J mice were divided into: G1: suture; G2: suture + HFB; G3: suture + HFB + doxycycline; G4: suture + HFB + wild type hESC; G5: suture + HFB + hESC off; G6: suture + HFB + hESC + doxycycline. |
Sensory function was enhanced in G5, resulting in heightened reflexes, upon paw stimulation ipsilateral to the lesion, as evidenced by von-Frey evaluation, which was corroborated by immunohistochemistry. |
Transgenic hESC could be used to support regeneration. HFB has the potential to aid nerve repair and is thought to promote superior functional recovery and improved motor neuron reinnervation when combined with this therapy. |
Leite et al. (2019) [23] |
To assess the effectiveness of HFB in association with suture, with 1 or 3 stitches after ischiatic nerve injury. |
Thirty-six Wistar rats were divided into: G1: control; G2: denervated (6 mm gap); G3: 3 stitches suture; G4: 1 stitch suture + HFB. |
G3 and G4 muscle analysis indicated an increase in muscle weight, frequency of fast fibers, and a decrease in collagen infiltration, while G4 had better nerve morphometric values compared to G3. |
The findings imply a protective effect at the site of the lesion due to the use of HFB. The reduction in sutures lessens the trauma inflicted by the needle and expedites the surgical procedure. |
Kempe et al. (2020) [24] |
To determine whether the combination of pharmacological treatment with dimethyl fumarate (DF) and root reimplantation using HFB could promote neuroprotection, preservation, and recovery of motor function. |
Seventy-nine adult female Lewis rats underwent ventral root avulsion of L4-L6 roots, followed by reimplantation and daily DF treatment for four weeks. HFB was utilized as an adjunct to ventral root reimplantation. |
The association between HFB and DF preserved motoneurons and synapses, reduced astrogliosis and microglial reactions, and downregulated the expression of pro-inflammatory gene transcripts. |
The association with HFB and DF demonstrated neuroprotective and immunomodulatory properties and 50% of motor function recovery following spinal cord root injury. |
Pinto et al. (2021) [25] |
To determine whether the combination of HFB with a single stitch has the potential to restore the function of the neuromuscular apparatus following sciatic nerve injury. |
Forty Wistar rats divided into G1: Control; G2: Denervated (6 mm gap); G3: 3 stitches suture; G4: 1 stitch suture + HFB. |
G1 exhibited normal morphology. In G2 flattening of the NMJ (fragmentation of nAChRs and tangled nerve terminals). G3 and G4: most parameter values were similar to G1 and G2. G3 and G4: planar area. |
G3 and G4 showed less fragmentation of nAChRs, and protein expression values suggested a return of nAChRs to a mat The use of HFB in conjunction with a single suture stitch reduced surgical time, minimized suture injuries, did not affect nerve regeneration, and showed potential for restoring the NMJ apparatus. |
Rodríguez-Sánchez et al. (2021) [26] |
To determine if Polycaprolactone Nerve Guidance Conduits (PCL-NGCs) produced by 3D printing with canine Adipose-derived Mesenchymal Stem Cells (AdMSCs) embedded in HFB could enhance nerve regeneration after sciatic nerve injury. |
Twenty-nine adult Wistar rats submitted to sciatic nerve injury were divided into G1: Sham; G2: autograft; G3: PCL (empty NGC); G4: PCL + HFB+ MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in HFB). |
G4 showed improved functional motor and electrophysiological recovery compared to the G3 after 12 weeks. G4 also increased the expression of neurotrophins and tended to higher reactivity of Schwann cells and axonal branching. |
PCL + HFB+ MSCs promoted neuroregenerative effects and amplified the trophic microenvironment, resulting in a pro-regenerative state. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. |
Leite et al. (2023) [10] |
To assess the impact of combining tubulization and HFB following peripheral nerve injury on the NMJ. |
Fifty-two adult male Wistar rats divided into G1: control; G2: denervated; G3: tubulization; and G4: tubulization + HFB. |
In G4 the NMJs presented morphological and morphometric similarities to G1 with an increase in S100 and AChRε protein expression and a decrease in MyoD. |
The HFB association with tubulization resulted in nAChRs stabilization highlighting the beneficial effect of HFB when used in conjunction with the tubulization technique. |
Tibúrcio et al. (2023) [13] |
To assess neuroregeneration and the immune response in the context of neuromuscular recovery, using HFB in conjunction with suturing for rat sciatic nerve repair. |
Forty male Wistar rats divided into groups of 7 or 30 days after nerve repair: G1: control; G2: denervated; G3: suture; G4: suture + HFB. |
G4 had the highest M2 macrophage area in both periods. After seven days, the G4 showed an increase in nerve area, number, and area of blood vessels. In this period, G4 was the only one similar to G1 in terms of the number of axons. After 30 days, the G4 was closer to the G1 concerning blood vessels and central myonuclear numbers, NMJ angle, and connective tissue volume. |
HFB enhances the immune response, increases axonal regeneration, induces angiogenesis, prevents severe muscle degeneration, and aids NMJ recovery. |
Kempe et al. (2023) [27] |
To examine the effects of combining surgical repair of lesioned roots with HFB and pharmacological treatment with dimethyl fumarate (DF). |
Forty adult females divided into G1: reimplantation + vehicle; G2: VRA without reimplantation + DF; G3: reimplantation + vehicle + HFB; G4: reimplantation + HFB + DF. |
HFB + DF association demonstrated: nerve sprouting, restoration of the ‘G’ ratio, and that most of the alpha motoneuron synapses were preserved in clusters. These parameters were associated with up to 50% of gait recovery, as the walking track test observed. |
Combining root restoration with HFB and DF administration proved to be neuroprotective and can enhance motoneuron survival and regeneration after proximal lesions. |
Bueno et al. (2023) [24] |
To investigate the application of HFB in the repair of the buccal branch of the facial nerve (BBFN) in conjunction with photobiomodulation (PBM), using a low-level laser (LLLT). |
Twenty-one rats divided into: G1: control; G2: LLLT; G3: denervated; G4: denervated + LLLT; G5: suture + HFB; G6: suture + HFB + LLLT. |
G5 and G6 presented normal parameters related to functional analysis. G6 showed an increase in nerve fiber diameter and axon diameter compared to G6. In terms of muscle fiber area, G6 was similar to G1. |
HFB+LLLT had positive effects on the morphological and functional stimulation of the BBFN, presenting a favorable alternative for the regeneration of severe injuries. |