Biomedical subjects

Mikael Wiberg

Publications and source records attributed to Mikael Wiberg.

At least 19 recordsLinked to original sources

PubMed2006

Volumetric magnetic resonance imaging of dorsal root ganglia for the objective quantitative assessment of neuron death after peripheral nerve injury.

Prevention of neuron death after peripheral nerve injury is vital to regaining adequate cutaneous innervation density and quality of sensation, and while experimentally proven neuroprotective therapies exist, there lacks suitable clinical outcome measures for translational research. Axotomized dorsal root ganglia (DRG) histologically exhibit volume reduction in proportion to the amount of neuronal death within them. Hence, this study evaluated the validity of using magnetic resonance imaging (MRI) to quantify DRG volume as a proxy measure of cell death. A high-resolution 3D MRI sequence was developed for volumetric quantification of the L4 DRG in the rat sciatic nerve model. An unoperated "control" group (n=4), and a "nerve transection" group (n=6), 4 weeks after axotomy, were scanned. Accuracy and validity of the technique were evaluated by comparison with morphological quantification of DRG volume and stereological counts of surviving neurons (optical fractionator). The technique was precise (coefficient of variation=4.3%), highly repeatable (9% variability), and sensitive (mean 15.0% volume reduction in axotomized ganglia detected with statistical significance: p<0.01). MRI showed strong and highly significant correlation with morphological measures of DRG volume loss (r=0.90, p<0.001), which in turn correlated well with neuron loss (r=0.75, p<0.05). MRI similarly exhibited direct correlation with neuron loss (r=0.67, p<0.05) with consistent agreement. MRI volumetric quantification of DRG is therefore a valid in vivo measure of neuron loss. As a non-invasive, objective measure of neuronal death after nerve trauma this technique has potential as a diagnostic modality and a quantitative tool for clinical studies of neuroprotective agents.

Animals↗

PubMed2006

Precision grip function after free toe transfer in children with hypoplastic digits.

Although toe-to-hand transfer has a defined role in the management of congenital hand deformities, it remains unclear how well children integrate the transferred digits into physiological grasping. We analysed fingertip forces in the precision grip of 13 patients when lifting a test object more than three years after free toe transfer for absent or hypoplastic digits. Clinically, most patients showed normal sensibility of transferred digits, but active motion and pinch strength were limited as compared to the normal hand. For the control of fingertip forces, two key features of the normal two-digit opposition grip were seen in all operated hands: adaptation of grip force to object weight and parallel coordination of lift and grip forces. These physiological grasping strategies developed independently of the patients' age at the time of operation, which ranged from one to 13 years. In four patients, we observed increased tangential load forces with the operated hand due to misalignments in the application of fingertips on the grasp surfaces. Such forces lead to increased grip force requirements on both fingers that may overload transferred digits with limited motor function. The need for optimal alignment of the grip axis during toe-transfer surgery is emphasised.

Adaptation, Physiological↗

PubMed2006

Delayed acetyl-L-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury.

Protection of sensory neurons after peripheral nerve injury is clinically crucial since inadequate sensory recovery is seriously affected by the death of up to 40% of sensory neurons. Immediate acetyl-L-carnitine (ALCAR) treatment eliminates this cell loss, but may not always be clinically feasible, hence we studied the effect of delaying the initiation of ALCAR treatment. Five groups of rats (n=5 per group) underwent unilateral sciatic nerve axotomy. ALCAR treatment (50 mg/kg/day) was initiated immediately, or after delays of 6 h, 24 h or 7 days after injury. A sham-treated group served as control. L4 and L5 dorsal root ganglia were harvested bilaterally 2 weeks after injury and stereological sensory neuron counts were obtained. Immediate sham treatment provided no neuroprotection (25% loss). Cell loss was eliminated when ALCAR was commenced within<or=24 h of axotomy. No statistically significant neuroprotective effect (18% loss) was evident compared to sham when ALCAR administration was initiated 7 days post-axotomy. When commenced within a clinically applicable time frame ALCAR treatment remains highly neuroprotective, potentially improving clinical outcome following peripheral nerve trauma.

Acetylcarnitine↗

PubMed2006

Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage.

We have investigated the phenotypic and bioassay characteristics of bone marrow mesenchymal stromal cells (MSCs) differentiated along a Schwann cell lineage using glial growth factor. Expression of the Schwann cell markers S100, P75, and GFAP was determined by immunocytochemical staining and Western blotting. The levels of the stem cell markers Stro-1 and alkaline phosphatase and the neural progenitor marker nestin were also examined throughout the differentiation process. The phenotypic properties of cells differentiated at different passages were also compared. In addition to a phenotypic characterization, the functional ability of differentiated MSCs has been investigated employing a co-culture bioassay with dissociated primary sensory neurons. Following differentiation, MSCs underwent morphological changes similar to those of cultured Schwann cells and stained positively for all three Schwann cell markers. Quantitative Western blot analysis showed that the levels of S100 and P75 protein were significantly elevated upon differentiation. Differentiated MSCs were also found to enhance neurite outgrowth in co-culture with sensory neurons to a level equivalent or superior to that produced by Schwann cells. These findings support the assertion that MSCs can be differentiated into cells that are Schwann cell-like in terms of both phenotype and function.

Alkaline Phosphatase↗

PubMed2006

Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation.

Development of biosynthetic conduits carrying extracellular matrix molecules and cell lines expressing neurotrophic growth factors represents a novel and promising strategy for spinal cord and peripheral nerve repair. In the present in vitro study, the compatibility and growth-promoting effects of (i) alginate hydrogel, (ii) alginate hydrogel complemented with fibronectin, and (iii) matrigel were compared between olfactory ensheathing cells (OECs), Schwann cells (SCs), and bone marrow stromal cells (BMSCs). Neurite outgrowth from embryonic dorsal root ganglia (DRG) neurons was used to assess the efficacy of the hydrogels alone or in combination with cultured cells to promote axonal regeneration. The result showed that alginate hydrogel transformed OECs, SCs, and BMSCs into atypical cells with spherical shape and inhibited their metabolic activity. Combination of alginate hydrogel with fibronectin promoted only OECs proliferation. Alginate hydrogel also inhibited outgrowth of DRG neurites, although this effect was attenuated by addition of fibronectin, SCs, or BMSCs. In contrast, matrigel stimulated cell proliferation, preserved the typical morphological features of the cultured cells and induced massive sprouting of DRG neurites. Addition of cultured cells to matrigel did not further improve DRG neurite outgrowth. The present findings suggest that addition of extracellular matrix should be considered when engineering biosynthetic scaffolds on the basis of alginate hydrogels.

Alginates↗

PubMed2005

The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats.

It has been proposed clinically that delayed surgery after traumatic brachial plexus injury may adversely affect functional outcome. In the present experimental study the neuroprotective and growth-promoting effects of early and delayed nerve grafting following proximal seventh cervical spinal nerve (C7) axotomy were examined. The ventral branch of C7 spinal nerve was transected and axons projecting out of the proximal nerve stump were labelled with Fast Blue (FB). At the same time, the biceps brachii muscle was denervated by transecting the musculocutaneous nerve at its origin. Neuronal survival and muscle atrophy were then assessed at 1, 4, 8 and 16 weeks after permanent axotomy. In the experimental groups, a peripheral nerve graft was interposed between the transected C7 spinal nerve and the distal stump of the musculocutaneous nerve at 1 week [early nerve repair (ENR)] or 8 weeks [delayed nerve repair (DNR)] after axotomy. Sixteen weeks after nerve repair had been performed, a second tracer Fluoro-Ruby (FR) was applied distal to the graft to assess the efficacy of axonal regeneration. Counts of FB-labelled neurons revealed that axotomy did not induce any significant cell loss at 4 weeks, but 15% of motoneurons and 32% of sensory neurons died at 8 weeks after injury. At 16 weeks, the amount of cell loss in spinal cord and dorsal root ganglion (DRG) reached 29 and 50%, respectively. Both ENR and DNR prevented retrograde degeneration of spinal motoneurons and counteracted muscle atrophy, but failed to rescue sensory neurons. Due to substantial cell loss at 8 weeks, the number of FR-labelled neurons after DNR was significantly lower when compared to ENR. However, the proportion of regenerating neurons among surviving motoneurons and DRG neurons remained relatively constant indicating that neurons retained their regenerative capacity after prolonged axotomy. The results demonstrate that DNR could protect spinal motoneurons and reduce muscle atrophy, but had little effect on sensory DRG neurons. However, the efficacy of neuroprotection and axonal regeneration will be significantly affected by the amount of cell loss already presented at the time of nerve repair.

Animals↗

PubMed2005

Composite PHB-GGF conduit for long nerve gap repair: a long-term evaluation.

Two to four cm nerve gaps in the rabbit common peroneal nerve were bridged with poly-3-hydroxybutyrate (PHB) conduits containing either glial growth factor (GGF) (PHB-GGF) or alginate matrix (PHB-ALG), and with empty PHB conduit (E-PHB). PHB-GGF significantly increased nerve regeneration up to 63 days following repair of long nerve gaps and the regeneration was sustained long term leading to motor organ reinnervation. At 120 days postoperatively, GGF addition significantly increased the quantity of Schwann cell and axonal regeneration compared to those in control conduits. In PHB-GGF conduits there were more minifascicles of myelinated fibres compared to the controls. The distal nerve of PHB-GGF and E-PHB conduits showed greater regeneration than that of PHB-ALG grafts, although all distal nerves contained fewer myelinated fibres than grafted conduits. Consistently, PHB-GGF conduits significantly reduced the muscle mass percentage loss compared to controls. In conclusion, GGF-containing conduits promoted sustained axonal regeneration and improved target muscle reinnervation.

Alginates↗

PubMed2004

Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration.

Bone marrow mesenchymal stem cells can trans-differentiate into neuronal phenotypes. We examined the differentiation of marrow stromal cells (MSCs) in culture and during nerve regeneration. MSCs from adult rats were exposed to glial growth factor (GGF) to stimulate glial differentiation. Subsequently differentiated MSCs were retrovirally labelled with green fluorescent protein and transplanted into 1 cm nerve conduits in the rat sciatic nerve. Fifteen days post-operatively the conduits were examined for axonal and Schwann cell regeneration and MSC integration. In vitro, MSCs exposed to GGF expressed S100 and glial fibrillary acidic protein. Following transplantation, MSCs maintained S100 expression and enhanced nerve regeneration, with significant Schwann cell regeneration compared to control (2.7 +/- 0.21 vs. 2.05 +/- .21 mm; P < 0.05). MSCs not exposed to GGF prior to transplantation expressed S100 in vivo indicating glial differentiation in response to local cytokines and growth factors.

Animals↗

PubMed2004

Phrenic nerve transfer in the treatment of brachial plexus avulsion: an experimental study of nerve regeneration and muscle morphology in rats.

The regeneration of motor and sensory neurons and the morphological changes of the target muscle after phrenic nerve transfer were investigated in adult rats. Six months following nerve transfer, 326.0 +/- 16.31 phrenic motoneurons regenerated into musculocutaneous nerve, which is not different from the normal number of phrenic motoneurons. The regenerated motoneurons exhibited a 14% nonsignificant hypertrophy. Of the dorsal root ganglia (DRG) neurons, 255.8 +/- 45.26 regenerated, which was significantly lower than the number of normal phrenic DRG neurons. The regenerated phrenic DRG neurons showed a 24% close-to-significant atrophy. The target muscle fiber morphology changed considerably after reinnervation. The present results suggest that the phrenic nerve has very good regenerative ability in terms of its motoneurons and a relatively insufficient sensory neuronal regeneration.

Animals↗

PubMed2003

Primary sensory neuronal rescue with systemic acetyl-L-carnitine following peripheral axotomy. A dose-response analysis.

The loss of a large proportion of primary sensory neurons after peripheral nerve axotomy is well documented. As a consequence of this loss, the innervation density attained on completion of regeneration will never be normal, regardless of how well the individual surviving neurons regenerate. Acetyl-L-carnitine (ALCAR), an endogenous peptide in man, has been demonstrated to protect sensory neurons, thereby avoiding loss after peripheral nerve injury. In this study we examined the dose-response effect of ALCAR on the primary sensory neurons in the rat dorsal root ganglia (DRG) 2 weeks after sciatic nerve axotomy. Six groups of adult rats (n=5) underwent unilateral sciatic nerve axotomy, without repair, followed by 2 weeks systemic treatment with one of five doses of ALCAR (range 0.5-50 mg/kg/day), or normal saline. L4 and L5 dorsal root ganglia were then harvested bilaterally and sensory neuronal cell counts obtained using the optical disector technique. ALCAR eliminated neuronal loss at higher doses (50 and 10 mg/kg/day), while lower doses did result in loss (12% at 5 mg/kg/day, p<0.05; 19% at 1 mg/kg/day, p<0.001; 23% at 0.5 mg/kg/day, p<0.001) compared to contralateral control ganglia. Treatment with normal saline resulted in a 25% (p<0.001) loss, demonstrating no protective effect in accordance with previous studies.ALCAR preserves the sensory neuronal cell population after axotomy in a dose-responsive manner and as such, has potential for improving the clinical outcome following peripheral nerve trauma when doses in excess of 10 mg/kg/day are employed.

Acetylcarnitine↗

PubMed2003

Sensory recovery after hand reimplantation: a clinical, morphological, and neurophysiological study in humans.

Despite fairly good return of motor function, patients who have amputated hands reimplanted demonstrate poor sensory recovery and severe cold intolerance, two variables that are difficult to quantify reliably. In this study we wanted to find out if there is a correlation between morphological findings of sensory and sympathetic reinnervation and clinical and neurophysiological variables. Skin was biopsied from the reimplanted and corresponding area in the normal hands of eight patients who had sustained a hand amputation and subsequent reimplantation. The sections were immunostained using markers for both sensory and sympathetic nerve fibres. Comparison between the reimplanted and normal sides in each individual showed a mean loss of sensory immunoreactive nerve fibres of 30%, and for sympathetic immunoreactivity the loss was 60%. There was measurable two-point discrimination in the injured hand only in patients below the age of 40 years, corresponding to the better recovery of mechanical thresholds evaluated neurophysiologically for this age group. These results confirm the extensive loss of sensory nerve fibres after nerve injury, probably correlated to loss of sensory neurons. We have also shown that it is possible to correlate the results of clinical and neurophysiological evaluation with morphological results of skin reinnervation specific to the repaired nerve, and so improve the possibility for the quantification of sensory recovery.

Adolescent↗

PubMed2003

Early nerve repair after injury to the postganglionic plexus: an experimental study of sensory and motor neuronal survival in adult rats.

The optimal time for brachial plexus nerve repair is debatable. In this study we examined whether early re-establishment of neurotrophic support from the periphery might reduce neuronal loss. In 14 adult rats, the C7 spinal nerve was transsected. All sensory cells of the dorsal root ganglion and spinal motor neurons projecting into the C7 nerve were labelled retrogradely. The proximal and distal portions of the C7 nerve were then reanastomosed by either primary repair or by a vascularised or conventional ulnar nerve graft. At 16 weeks postoperatively, the nerve repair had significantly reduced the loss of both sensory and motor C7 neurons. Most striking was that a 30% motor neuronal loss in the control was almost eliminated by early nerve repair. In the grafted animals, half of the surviving neurons had regenerated through the graft, with no difference between vascularised and conventional nerve grafts. These results suggest that early surgical intervention may promote neuronal survival and regeneration after injuries to the brachial plexus.

Anastomosis, Surgical↗

PubMed2003

Addition of fibronectin to alginate matrix improves peripheral nerve regeneration in tissue-engineered conduits.

Schwann cell (SC) transplantation has been proposed to encourage peripheral nerve regeneration, but an optimal SC-carrying matrix would be needed. The aim of this study was to characterize how the addition of fibronectin to alginate would affect the outcome of nerve regeneration promoted by Schwann cells embedded in this matrix. Genetically labeled rat SCs were obtained by lacZ gene transduction. SCs were suspended in alginate hydrogel matrix with/without addition of liquid fibronectin, and their viability and growth in the different types of matrices were assessed in vitro by AlamarBlue assay. In vivo assessment of SC transplantation in the matrix was carried out with poly-3-hydroxybutyrate (PHB) conduits to bridge a sciatic nerve gap. The grafted conduits were harvested at 2, 3, and 6 weeks and assessed for the presence of labeled SCs in relation to regrowing axons. The amount and rate of axonal regeneration were assessed by quantitative immunohistochemistry. Addition of fibronectin to alginate hydrogel improved SC viability and growth profile in vitro. X-Gal staining confirmed that SCs transplanted in PHB conduits were viable throughout the time course, and that the labeled SCs were clearly associated with regenerating axons. The regeneration rate was enhanced when liquid fibronectin was added to the alginate matrix. Furthermore, the presence of SCs also enhanced regeneration and there was an additive effect when both SCs and fibronectin were combined with alginate. In conclusion, the addition of fibronectin to alginate hydrogel matrix contributed to improve nerve regeneration, supporting SC viability and augmenting their effect on axonal growth when transplanted in a bioengineered nerve conduit.

Alginates↗

PubMed2003

Will it be possible to produce peripheral nerves?

Several hundred thousand peripheral nerve injuries occur each year in Europe and the United States alone, mainly as a result of trauma to the upper extremity. Even after optimal surgical repair, functional outcome--especially sensory recovery--is disappointingly poor. This poor outcome is largely due to death of primary sensory neurons, but also lack of fiber regeneration over the nerve trauma zone and target-organ denervation. The type of nerve repair performed is dependent on the size of the nerve gap between the proximal and distal stumps. Short gaps can be repaired directly by end-to-end coaptation and epineural suturing, whereas long nerve gaps require additional material to bridge the defect, which further reduces the functional outcome. The current repair method to bridge nerve defects is the use of autologous nerve grafts (autografts), which provide the regenerating axons with a natural guidance channel populated with functioning Schwann cells (SC) surrounded by their basal lamina. The first use of nerve grafts in humans was reported in 1878, but the wide use of this technique was developed during World War II when nerve grafting became the standard method for nerve-gap repair. Harvesting of nerve grafts results in co-morbidity that includes scarring, loss of sensation, and possible formation of painful neuroma. The donor nerves often are of small calibre and limited number. As functional recovery in peripheral nerve reconstruction is poor, clearly, alternative method for bridging nerve gaps is needed.

Animals↗

PubMed2002

Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl-L-carnitine treatment.

Peripheral nerve trauma remains a major cause of morbidity, largely due to the death of approximately 40% of innervating sensory neurons, and to slow regeneration after repair. Acetyl-L-carnitine (ALCAR) is a physiological peptide that virtually eliminates sensory neuronal death, and may improve regeneration after primary nerve repair. This study determines the effect of ALCAR upon regeneration after secondary nerve repair, thereby isolating its effect upon neuronal regenerative capacity. Two months after unilateral sciatic nerve division 1 cm nerve graft repairs were performed (n=5), and treatment with 50 mg/kg/day ALCAR was commenced for 6 weeks until harvest. Regeneration area and distance were determined by quantitative immunohistochemistry. ALCAR treatment significant increased immunostaining for both nerve fibres (total area 264% increase, P<0.001; percentage area 229% increase, P<0.001), and Schwann cells (total area 111% increase, P<0.05; percentage area 86% increase, P<0.05), when compared to no treatment. Regeneration into the distal stump was greatly enhanced (total area 2,242% increase, P=0.008; percentage area 3,034% increase, P=0.008). ALCAR significantly enhances the regenerative capacity of neurons that survive peripheral nerve trauma, in addition to its known neuroprotective effects.

Acetylcarnitine↗

PubMed2002

Systemic acetyl-L-carnitine eliminates sensory neuronal loss after peripheral axotomy: a new clinical approach in the management of peripheral nerve trauma.

Several hundred thousand peripheral nerve injuries occur each year in Europe alone. Largely due to the death of around 40% of primary sensory neurons, sensory outcome remains disappointingly poor despite considerable advances in surgical technique; yet no clinical therapies currently exist to prevent this neuronal death. Acetyl- L-carnitine (ALCAR) is a physiological peptide with roles in mitochondrial bioenergetic function, which may also increase binding of nerve growth factor by sensory neurons. Following unilateral sciatic nerve transection, adult rats received either one of two doses of ALCAR or sham, or no treatment. Either 2 weeks or 2 months later, L4 and L5 dorsal root ganglia were harvested bilaterally, in accordance with the Animal (Scientific Procedures) Act 1986. Neuronal death was quantified with a combination of TUNEL [TdT (terminal deoxyribonucleotidyl transferase) uptake nick end labelling] and neuron counts obtained using the optical disector technique. Sham treatment had no effect upon neuronal death. ALCAR treatment caused a large reduction in the number of TUNEL-positive neurons 2 weeks after axotomy (sham treatment 33/group; low-dose ALCAR 6/group, P=0.132; high-dose ALCAR 3/group, P<0.05), and almost eliminated neuron loss (sham treatment 21%; low-dose ALCAR 0%, P=0.007; high-dose ALCAR 2%, P<0.013). Two months after axotomy the neuroprotective effect of high-dose ALCAR treatment was preserved for both TUNEL counts (no treatment five/group; high-dose ALCAR one/group) and neuron loss (no treatment 35%; high-dose ALCAR -4%, P<0.001). These results provide further evidence for the role of mitochondrial bioenergetic dysfunction in post-traumatic sensory neuronal death, and also suggest that acetyl- L-carnitine may be the first agent suitable for clinical use in the prevention of neuronal death after peripheral nerve trauma.

Acetylcarnitine↗

PubMed2002

Effect of allogeneic Schwann cell transplantation on peripheral nerve regeneration.

Transplantation of allogeneic Schwann cells (SC) would make it feasible to reconstruct immediately peripheral nerve defects, compared to using autologous SC; however, this treatment modality has not been adequately evaluated. The aim of this study was to characterize and compare the effects of allogeneic versus syngeneic SC transplantation following peripheral nerve injury. Polyhydroxybutyrate conduits were used to bridge a 10-mm gap in the rat sciatic nerve. The conduits were filled with alginate hydrogel with or without cultured allogeneic or syngeneic genetically labeled SC, without the use of immunosuppressive therapy, and examined after 2, 3, and 6 weeks with 5-bromo-4-chloro-3-indoyl-beta-D-galactosidase chemical staining and immunohistochemistry to quantify SC migration into the conduit, axonal regeneration, the state of SC differentiation, and the expression of major histocompatibility complexes (MHC) I and II, as well as to quantify macrophage and B- and T-lymphocyte infiltration. Allogeneic SC were rejected by 6 weeks, whereas syngeneic SC could still be identified. Allogeneic and syngeneic SC equally enhanced the axonal regeneration distance but the quantity of axons was greater using syngeneic SC. The ingrowth of SC into the conduits containing allogeneic SC was similar to that observed in the presence of syngeneic SC, indicating the absence of deleterious immune response. SC continued to express phenotypic markers of nonmyelination and these were highest in conduits with allogeneic SC. Expression of MHC I and II was higher in the conduits with allogeneic SC at 3 weeks and without significant difference in the number of macrophages and lymphocytes, except at 6 weeks, when there was a larger number of lymphocytes using syngeneic SC. In conclusion, allogeneic SC enhanced axonal regeneration distance and did not induce a deleterious immune response. In a clinical setting the immediate availability of allogeneic SC for transplantation may compensate for the better outcome achieved by the use of autologous SC that require a longer preparation time in culture.

Alginates↗

PubMed2002

A novel biodegradable implant for neuronal rescue and regeneration after spinal cord injury.

After spinal cord injury, the severed neuronal pathways fail to regenerate spontaneously. This study describes a biodegradable implant using poly-beta-hydroxybutyrate (PHB) fibers as carrier scaffold for matrix components and cell lines supporting neuronal survival and regeneration after spinal cord injury. After cervical spinal cord injury in adult rats, a graft consisting of PHB fibers coated with alginate hydrogel + fibronectin was implanted in the lesion cavity. In control groups, PHB was omitted and only alginate hydrogel or fibronectin, or their combination, were used for grafting. In addition, comparisons were made with animals treated intrathecally after spinal cord injury with the neurotrophic factors BDNF or NT-3. The neurons of the rubrospinal tract served as experimental model. In untreated animals, 45% of the injured rubrospinal neurons were lost at 8 weeks postoperatively. Implantation of the PHB graft reduced this cell loss by 50%, a rescuing effect similar to that obtained after treatment with BDNF or NT-3. In the absence of PHB support, implants of only alginate hydrogel or fibronectin, or their combination, had no effect on neuronal survival. After addition of neonatal Schwann cells to the PHB graft, regenerating axons were seen to enter the graft from both ends and to extend along its entire length. These results show that implants using PHB as carrier scaffold and containing alginate hydrogel, fibronectin and Schwann cells can support neuronal survival and regeneration after spinal cord injury

Animals↗