MicroRNA和雪旺细胞自噬与周围神经再生修复的研究进展

正周围神经损伤会使神经支配区域的运动、感觉机能下降和缺失,严重影响生产和生活质量。现代显微外科技术的应用已大大提高了修复效果,但由于周围神经的特殊结构和功能,目前的修复技术对于神经功能的恢复效果仍然有限,这引起了研究者们对于周围神经损伤后再生修复机制的探索。周围神经损伤后,损伤处残存雪旺细胞(Schwann cells)的数量和增殖分化能力是影响神经再生修复的关键因素[1]。在周围神经损伤后的雪旺细胞内发现大量溶     

雪旺氏细胞在周围神经损伤修复中的作用及其分子机制

雪旺氏细胞是周围神经系统中特有的胶质细胞,在周围神经损伤后的变性和再生中有着非常重要的作用。周围神经的再生主要依赖于雪旺氏细胞提供了适宜的微环境,如分泌多种神经营养因子和其它相关因子,位于轴突和雪旺氏细胞之间的紧密连接加强信息传递,雪旺氏细胞形成Büngner带为轴突生长的通道,并形成髓鞘等。本文阐述了雪旺氏细胞在周围神经再生中的重要功能以及相关机制,展望围绕雪旺氏细胞的未来研究方向,临床应用的潜在价值。     

Skin-derived Precursors as a Source of Progenitors for Cutaneous Nerve Regeneration

Peripheral nerves have the potential to regenerate axons and reinnervate end organs. Chronic denervation and disturbed nerve regeneration are thought to contribute to peripheral neuropathy, pain, and pruritus in the skin. The capacity of denervated distal nerves to support axonal regeneration requires proliferation by Schwann cells, which guide regenerating axons to their denervated targets. However, adult peripheral nerve Schwann cells do not retain a growth-permissive phenotype, as is required to produce new glia. Therefore, it is believed that following injury, mature Schwann cells dedifferentiate to a progenitor/stem cell phenotype to promote axonal regrowth. In this study, we show that skin-derived precursors (SKPs), a recently identified neural crest-related stem cell population in the dermis of skin, are an alternative source of progenitors for cutaneous nerve regeneration. Using in vivo and in vitro three-dimensional cutaneous nerve regeneration models, we show that the SKPs are neurotropic toward injured nerves and that they have a full capacity to differentiate into Schwann cells and promote axon regeneration. The identification of SKPs as a physiologic source of progenitors for cutaneous nerve regeneration in the skin, where SKPs physiologically reside, has important implications for understanding early cellular events in peripheral nerve regeneration. It also provides fertile ground for the elucidation of intrinsic and extrinsic factors within the nerve microenvironment that likely play essential roles in cutaneous nerve homeostasis. STEM Cells2012;30:2261-2270.     

Collagen nerve conduits--assessment of biocompatibility and axonal regeneration

Bridging of nerve gaps is still a major problem in peripheral nerve surgery. Alternatively to autologous nerve grafts tissue engineering of peripheral nerves focuses on biocompatible conduits to reconstruct nerves. Such non-neural conduits fail to support regeneration over larger gaps due to lacking viable Schwann cells that promote regeneration by producing growth factors and cell guiding molecules. This problem may be overcome by implantation of cultivated Schwann cells into suitable scaffolds. In the present experiments we tested a collagen type I/III tube as a potential nerve guiding matrix. Revascularization, tolerance and Schwann cell settlement were evaluated by light, fluorescence and scanning electron microscopy after different implantation times. The conduits were completely revascularized between day 5 and 7 post-operatively and well integrated into the host tissue. Implanted Schwann cells adhered, survived and proliferated on the inner surface of the conduits. Nevertheless, bridging a 2 cm gap of the sciatic nerve of adult Wistar rats with these collagen/Schwann cell conduits led to a disappointing regeneration compared to controls with autologous grafts. From these results, we conclude that a sufficient biocompatibility of bioartificial nerve conduits is a necessary prerequisite, however, it remains only one of several parameters important for peripheral nerve regeneration.     

Central and peripheral nerve regeneration by transplantation of Schwann cells and transdifferentiated bone marrow stromal cells

In contrast to the peripheral nervous system (PNS), little structural and functional regeneration of the central nervous system (CNS) occurs spontaneously following injury in adult mammals. The inability of the CNS to regenerate is mainly attributed to its own inhibitorial environment such as glial scar formation and the myelin sheath of oligodendrocytes. Therefore, one of the strategies to promote axonal regeneration of the CNS is to experimentally modify the environment to be similar to that of the PNS. Schwann cells are the myelinating glial cells in the PNS, and are known to play a key role in Wallerian degeneration and subsequent regeneration. Central nervous system regeneration can be elicited by Schwann cell transplantation, which provides a suitable environment for regeneration. The underlying cellular mechanism of regeneration is based upon the cooperative interactions between axons and Schwann cells involving the production of neurotrophic factors and other related molecules. Furthermore, tight and gap junctional contact between the axon and Schwann cell also mediates the molecular interaction and linking. In this review, the role of the Schwann cell during the regeneration of the sciatic (representing the PNS) and optic (representing the CNS) nerves is explained. In addition, the possibility of optic nerve reconstruction by an artificial graft of Schwann cells is also described. Finally, the application of cells not of neuronal lineage, such as bone marrow stromal cells (MSCs), in nerve regeneration is proposed. Marrow stromal cells are known as multipotential stem cells that, under specific conditions, differentiate into several kinds of cells. The strategy to transdifferentiate MSCs into the cells with a Schwann cell phenotype and the induction of sciatic and optic nerve regeneration are described.     

Supplementation of acellular nerve grafts with skin derived precursor cells promotes peripheral nerve regeneration

Introduction of autologous stem cells into the site of a nerve injury presents a promising therapy to promote axonal regeneration and remyelination following peripheral nerve damage. Given their documented ability to differentiate into Schwann cells (SCs) in vitro, we hypothesized that skin-derived precursor cells (SKPs) could represent a clinically-relevant source of transplantable cells that would enhance nerve regeneration following peripheral nerve injury. In this study, we examined the potential for SKP-derived Schwann cells (SKP–SCs) or nerve-derived SCs to improve nerve regeneration across a 12 mm gap created in the sciatic nerve of Lewis rats bridged by a freeze-thawed nerve graft. Immunohistology after 4 weeks showed survival of both cell types and early regeneration in SKP seeded grafts was comparable to those seeded with SCs. Histomorphometrical and electrophysiological measurements of cell-treated nerve segments after 8 weeks survival all showed significant improvement as compared to diluent controls. A possible mechanistic explanation for the observed results of improved regenerative outcomes lies in SKP–SCs' ability to secrete bioactive neurotrophins. We therefore conclude that SKPs represent an easily accessible, autologous source of stem cells for transplantation therapies which act as functional Schwann cells and show great promise in improving regeneration following nerve injury.     

The possible influence of varying diameter of aligned electrospun fibers on Schwann cells maturation in culture

The development of Schwann cells, the principal glial cell in the peripheral nervous system, occurs through a series of transitional embryonic and postnatal phases, which are tightly regulated by a number of axonal signals. During the axon ensheathment and myelin growth, the diameter of the axon play an important role in the maturation of Schwann cells. Because of electrospun fibers similar to protein fibers within the native extracellular matrix, the scaffolds are being developed as neural tissue engineering scaffolds. Until now, the correlation between varying diameter of aligned electrospun fibers and Schwann cells maturation has not been investigated. We hypothesize that the different diameter of aligned electrospun fibers may influence the maturation of Schwann cells and may help improve the outcome of cell-based approaches to cure demyelinated lesions or peripheral nerve regeneration.     

组织工程化人工神经研究进展

利用各种神经导管可成功桥接修复短段周围神经缺损已为许多学者公认 ,但是 ,这些神经导管由于缺乏许旺细胞或内部支架来支持、促进神经再生轴突长距离生长 ,因此不能有效修复长段周围神经缺损[1,2 ] 。应用组织工程技术构建神经导管 ,为修复长段周围神经缺损提供了新的方法和思路。这项研究的核心是模拟周围神经天然结构 ,将许旺细胞与生物支架材料有机结合成为类似Ｂ櫣ｎｇｎｅｒ带的结构 ,为再生神经提供良好的生长环境 ,充分发挥许旺细胞对再生神经的营养 ,诱导作用 ,从而促进神经的再生。组织工程化人工神经的主要内容是将经体外培养扩…     

坐骨神经再生过程中施万细胞自噬的形态学观察

目的：探讨大鼠坐骨神经再生过程中的细胞自噬作用。方法：横切大鼠坐骨神经制作神经损伤再生模型，分别于造模后0、0．5、1．0、1．5、2．0、3．0、4、5、7、10、15d取近断端组织行电镜结构观察。结果：轴突在第1天时从髓鞘脱离，溃变呈空泡状。第2天开始髓鞘皱褶、绞窄并脱落形成碎片，施万细胞内可见大小形状各异的髓鞘碎片，并与大量溶酶体融合形成自噬泡，呈酸性磷酸酶（AcPase）阳性。第7d时幼稚细胞出现于新生毛细血管周围，大量幼稚细胞随后出现。结论：施万细胞自噬对坐骨神经再生时溃变髓鞘的清除起主要作用，溶酶体显著地参与了该过程，施万细胞脱分化为幼稚的祖细胞后大量增殖分化参与神经再生过程。     

The role of basic fibroblast growth factor in peripheral nerve regeneration

In the peripheral nervous system regeneration and gradual functional restoration occur following peripheral nerve injury. Growth of regenerating axons depends on the presence of diffusible neurotrophic factors, in addition to the substratum. Neurotrophic factors that are involved in peripheral nerve regeneration include nerve growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor, glial cell line-derived neurotrophic factor, and interleukin-6. Recent functional and expression studies of basic fibroblast growth factor and its receptors have emphasized a physiological role of these molecules in the peripheral nervous system. Basic fibroblast growth factor and its receptors are constitutively expressed in dorsal root ganglia and the peripheral nerve. These molecules display an upregulation in dorsal root ganglia and in the proximal and distal nerve stumps following peripheral nerve injury. In the ganglia these molecules show a mainly neuronal expression, whereas at the lesion site of the nerve, Schwann cells and invading macrophages represent the main cellular sources of basic fibroblast growth factor and the receptors 1–3. Exogenously applied basic fibroblast growth factor mediates rescue effects on injured sensory neurons and supports neurite outgrowth of transectioned nerves. Regarding the expression pattern and the effects after exogenous administration of basic fibroblast growth factor, this molecule seems to play a physiological role during nerve regeneration. Thus, basic fibroblast growth factor could be a promising candidate to contribute to the development of new therapeutic strategies for the treatment of peripheral nerve injuries.     

Endopeptidase-24.11 is suppressed in myelin-forming but not in non-myelin-forming Schwann cells during development of the rat sciatic nerve.

Endopeptidase-24.11, which is identical with the common acute lymphoblastic leukemia antigen (CALLA), is a cell surface zinc metalloprotease that has the ability to hydrolyse a variety of physiologically active peptides. Interest in this enzyme is based on the view that it may play a role in the regulation of peptide signals in different tissues, including the nervous and immune systems. We have previously shown that endopeptidase-24.11 is present in Schwann cells in the peripheral nervous system of newborn pigs [Kioussi C. and Matsas R. (1991) J. Neurochem. 57, 431-440]. In the present study we have investigated the developmental expression of the endopeptidase by Schwann cells in the rat sciatic nerve, from embryonic day 16 to maturity. Endopeptidase-24.11 was monitored enzymatically as well as by immunoblotting and immunocytochemistry using the monoclonal anti-endopeptidase antibody 23B11. We found an age-dependent decline in both the enzyme activity and the levels of immunoreactive protein. Endopeptidase-24.11 was first detected at embryonic day 18 and was present in all neonatal and early postnatal Schwann cells. However, as myelination proceeded the endopeptidase was gradually suppressed in the majority of cells that form myelin but retained in non-myelin-forming cells in the adult animal. At this stage, only very few large diameter myelinated fibers expressed weakly endopeptidase-24.11. Schwann cells dissociated from postnatal day 5 nerves and cultured up to one week in the absence of axons expressed endopeptidase-24.11. These results show that the endopeptidase has a distinct developmental profile in the rat sciatic nerve, similar to that of a group of other Schwann cell surface antigens, including the cell adhesion molecules N-CAM and L1 and the nerve growth factor receptor. We suggest that, as is the case with these antigens, endopeptidase-24.11 may play a role in nerve development and/or regeneration. In addition, persistence of endopeptidase-24.11 in a minority of adult myelin-forming Schwann cells suggests a possible role for the enzyme in axon-myelin apposition and maintenance, especially of larger diameter axons.     

Electrospinning of Matrigel to Deposit a Basal Lamina-Like Nanofiber Surface

Schwann cell basal lamina is a nanometer-thin extracellular matrix layer that separates the axon-bound Schwann cells from the endoneurium of the peripheral nerve. It is implicated in the promotion of nerve regeneration after transection injury by allowing Schwann cell colonization and axonal guidance. Hence, it is desired to mimic the native basal lamina for neural tissue engineering applications. In this study, basal lamina proteins from BD Matrigel (growth factor-reduced) were extracted and electrospun to deposit nonwoven nanofiber mats. Adjustment of solute protein concentration, potential difference, air gap distance and flow rate produced a basal lamina-like construct with an average surface roughness of 23 nm and composed of 100-nm-thick irregular and relatively discontinuous fibers. Culture of embryonic chick dorsal root ganglion explants demonstrated that the fabricated nanofiber layer supported explant attachment, elongation of neurites, and migration of satellite Schwann cells in a similar fashion compared to electrospun collagen type-I fibers. Furthermore, the presence of nanorough surface featues significantly increased the neurite spreading and Schwann cell growth. Sciatic nerve segment incubation also showed that the construct is promigratory to nerve Schwann cells. Results, therefore, suggest that the synthetic basal lamina fibers can be utilized as a biomaterial for induction of peripheral nerve repair.     

重组睫状神经营养因子对周围神经再生中多种细胞的作用

为了解重组睫状神经营养因子 ( CNTF)对周围神经再生中多种细胞的作用 ,用硅管套接切断的成年大鼠坐骨神经 ,在受损神经局部一次性给予重组睫状神经营养因子 :用免疫组织化学 ABC法结合计算机图像分析观测再生神经中 GAP-4 3、S10 0、CD68、MHC- 免疫反应阳性物质的变化。与生理盐水对照组相比 ,证明 CNTF组再生神经中上述四种物质显著增多。结果提示重组睫状神经营养因子能促进轴突的再生、Schwann细胞的迁入、单核细胞的渗出和活化     

Synergistic improvements in cell and axonal migration across sciatic nerve lesion gaps using bioresorbable filaments and heregulin-beta1

The success of entubulation for peripheral nerve regeneration is still limited, especially with long lesion gaps. In this study, we examined if regeneration could be enhanced by constructing implants to both align axonal growth and promote Schwann cell proliferation and migration. Silicone implants were used to bridge a 1.4-cm gap in the rat sciatic nerve. Adult female Sprague-Dawley rats were divided into four groups of tubes containing either 1) Matrigel; 2) Matrigel and heregulin; 3) Matrigel and poly(L-lactic acid) (PLLA) microfilaments; or 4) Matrigel, PLLA microfilaments, and heregulin. Ten weeks postimplantation, the number of axons and Schwann cells were measured at the distal end of implants. Implants with microfilaments displayed better tissue cable formation, increased Schwann cell migration, and regeneration of anti-calcitonin gene-related peptide-positive axons, but not RMDO95-positive axons compared with nonfilament-containing groups. Heregulin treatment caused an increase in Schwann cell number, but it demonstrated no significant improvement in either tissue cable formation or axon number. Extensive regeneration was observed through implants containing Matrigel, microfilaments, and heregulin, which induced significant improvements in the number and longitudinal organization of both Schwann cells and axons. These results indicate that physical guidance of microfilaments and the Schwann cell growth factor, heregulin, act synergistically to improve nerve regeneration across long lesion gaps.     

Peripheral nerve explants grafted into the vitreous body of the eye promote the regeneration of retinal ganglion cell axons severed in the optic nerve

Summary We have conducted experiments in the adult rat visual system to assess the relative importance of an absence of trophic factors versus the presence of putative growth inhibitory molecules for the failure of regeneration of CNS axons after injury. The experiments comprised three groups of animals in which all optic nerves were crushed intra-orbitally: an optic nerve crush group had a sham implant-operation on the eye; the other two groups had peripheral nerve tissue introduced into the vitreous body; in an acellular peripheral nerve group, a frozen/thawed teased sciatic nerve segment was grafted, and in a cellular peripheral nerve group, a predegenerate teased segment of sciatic nerve was implanted. The rats were left for 20 days and their optic nerves and retinae prepared for immunohistochemical examination of both the reaction to injury of axons and glia in the nerve and also the viability of Schwann cells in the grafts. Anterograde axon tracing with rhodamine-B provided unequivocal qualitative evidence of regeneration in each group, and retrograde HRP tracing gave a measure of the numbers of axons growing across the lesion by counting HRP filled retinal ganglion cells in retinal whole mounts after HRP injection into the optic nerve distal to the lesion. No fibres crossed the lesion in the optic nerve crush group and dense scar tissue was formed in the wound site. GAP-43-positive and rhodamine-B filled axons in the acellular peripheral nerve and cellular peripheral nerve groups traversed the lesion and grew distally. There were greater numbers of regenerating fibres in the cellular peripheral nerve compared to the acellular peripheral nerve group. In the former, 0.6–10% of the retinal ganglion cell population regenerated axons at least 3–4 mm into the distal segment. In both the acellular peripheral nerve and cellular peripheral nerve groups, no basal lamina was deposited in the wound. Thus, although astrocyte processes were stacked around the lesion edge, a glia limitans was not formed. These observations suggest that regenerating fibres may interfere with scarring. Viable Schwann cells were found in the vitreal grafts in the cellular peripheral nerve group only, supporting the proposition that Schwann cell derived trophic molecules secreted into the vitreous stimulated retinal ganglion cell axon growth in the severed optic nerve. The regenerative response of acellular peripheral nerve-transplanted animals was probably promoted by residual amounts of these molecules present in the transplants after freezing and thawing. In the optic nerves of all groups the astrocyte, microglia and macrophage reactions were similar. Moreover, oligodendrocytes and myelin debris were also uniformly distributed throughout all nerves. Our results suggest either that none of the above elements inhibit CNS regeneration after perineuronal neurotrophin delivery, or that the latter, in addition to mobilising and maintaining regeneration, also down regulates the expression of axonal growth cone-located receptors, which normally mediate growth arrest by engaging putative growth inhibitory molecules of the CNS neuropil.     

Biphasic electrical targeting plays a significant role in schwann cell activation

Electrical stimulation (ES) is a promising technique for axonal regeneration of peripheral nerve injuries. However, long-term, continuous ES in the form of biphasic electric current (BEC) to stimulate axonal regeneration has rarely been attempted and the effects of BEC on Schwann cells are unknown. We hypothesized that long-term, continuous ES would trigger the activation of Schwann cells, and we therefore investigated the effect of BEC on the functional differentiation of primary human mesenchymal stromal cells (hMSCs) into Schwann cells, as well as the activity of primary Schwann cells. Differentiation of hMSCs into Schwann cells was determined by coculture with rat pheochromocytoma cells (PC12 cell line). We also investigated the in vivo effects of long-term ES (4 weeks) on axonal outgrowth of a severed sciatic nerve with a 7-mm gap after retraction of the nerve ends in rats by implanting an electronic device to serve as a neural conduit. PC12 cells cocultured with hMSCs electrically stimulated during culture in Schwann cell differentiation medium (Group I) had longer neurites and a greater percentage of PC12 cells were neurite-sprouting than when cocultured with hMSCs cultured in growth medium (control group) or unstimulated hMSCs in the same culture conditions as used for Group I (Group II). Group I cells showed significant upregulation of Schwann cell-related neurotrophic factors such as nerve growth factor and glial-derived neurotrophic factor compared to Group II cells at both the mRNA and protein levels. Primary Schwann cells responded to continuous BEC with increased proliferation and the induction of nerve growth factor and glial-derived neurotrophic factor, similar to Group I cells, and in addition, induction of brain-derived neurotrophic factor was observed. Immunohistochemical investigation of sciatic nerve regenerates revealed that BEC increased axonal outgrowth significantly. These results demonstrate that BEC enhanced the functional activity of Schwann cells via the induction of neurotrophic factor release and guide-increased axonal outgrowth in vivo. The effectiveness of long-term ES highlights the feasibility of a BEC-based therapeutic device to accelerate nerve regeneration of severed peripheral nerve injuries with a gap.     

Standardized criterion to analyze and directly compare various materials and models for peripheral nerve regeneration

Progress in understanding conditions for optimal peripheral nerve regeneration has been stunted due to lack of standardization of experimental conditions and assays. In this paper we review the large database that has been generated using the Lundborg nerve chamber model and compare various theories for their ability to explain the experimental data. Data were normalized based on systematic use of the critical axon elongation, the gap length at which the probability of axon reconnection between the stumps is just 50%. Use of this criterion has led to a rank-ordering of devices or treatments and has led, in turn, to conclusions about the conditions that facilitate regeneration. Experimental configurations that have maximized facilitation of peripheral nerve regeneration are those in which the tube wall comprised degradable polymers, including collagen and certain synthetic biodegradable polymers, and was cell-permeable rather than protein-permeable. Tube fillings that showed very high regenerative activity were suspensions of Schwann cells, a solution either of acidic or basic fibroblast growth factor, insoluble ECM substrates rather than solutions or gels, polyamide filaments oriented along the tube axis and highly porous, insoluble analogs of the ECM with specific structure and controlled degradation rate. It is suggested that the data are best explained by postulating that the quality of regeneration depends on two critical processes. The first is compression of stumps and regenerating nerve by a thick myofibroblast layer that surrounds these tissues and blocks synthesis of a nerve of large diameter (pressure cuff theory). The second is synthesis of linear columns of Schwann cells that serve as tracks for axon elongation (basement membrane microtube theory). It is concluded that experimental configurations that show high regenerative activity suppress the first process while facilitating the second.     

Micropatterned polymer substrates control alignment of proliferating Schwann cells to direct neuronal regeneration

Microcontact printed polymeric substrates were evaluated for their ability to control Schwann cell attachment and direct proliferation, as Schwann cell guidance is a crucial factor in directing peripheral nerve regeneration. Elastomeric stamps of poly(dimethylsiloxane) were "inked" with laminin, a permissive protein for Schwann cell adhesion, and stamped onto poly(methyl methacrylate) substrates to create patterns of lines and intervals varying from 10 to 50 microm wide. Schwann cells were seeded onto the substrates in serum-free media. After 4h, media was replaced with serum-containing growth media and changed daily thereafter. The addition of growth media to stimulate proliferation initially caused some loss in cell orientation relative to the laminin pattern, but when monolayer formation was complete, a high degree of cell orientation was observed. As both cell-cell contacts and surface coverage were maximized, the Schwann cells achieved an even higher order of orientation than observed during the early stages of proliferation. Significantly, smaller pattern widths increased the degree of orientation, regardless of interval width. Our results indicate that patterned polymeric substrates may enhance peripheral nerve regeneration by creating a highly ordered Schwann cell matrix for guidance of neurons.     

Standardized criterion to analyze and directly compare various materials and models for peripheral nerve regeneration

Progress in understanding conditions for optimal peripheral nerve regeneration has been stunted due to lack of standardization of experimental conditions and assays. In this paper we review the large database that has been generated using the Lundborg nerve chamber model and compare various theories for their ability to explain the experimental data. Data were normalized based on systematic use of the critical axon elongation, the gap length at which the probability of axon reconnection between the stumps is just 50%. Use of this criterion has led to a rank-ordering of devices or treatments and has led, in turn, to conclusions about the conditions that facilitate regeneration. Experimental configurations that have maximized facilitation of peripheral nerve regeneration are those in which the tube wall comprised degradable polymers, including collagen and certain synthetic biodegradable polymers, and was cell-permeable rather than protein-permeable. Tube fillings that showed very high regenerative activity were suspensions of Schwann cells, a solution either of acidic or basic fibroblast growth factor, insoluble ECM substrates rather than solutions or gels, polyamide filaments oriented along the tube axis and highly porous, insoluble analogs of the ECM with specific structure and controlled degradation rate. It is suggested that the data are best explained by postulating that the quality of regeneration depends on two critical processes. The first is compression of stumps and regenerating nerve by a thick myofibroblast layer that surrounds these tissues and blocks synthesis of a nerve of large diameter (pressure cuff theory). The second is synthesis of linear columns of Schwann cells that serve as tracks for axon elongation (basement membrane microtube theory). It is concluded that experimental configurations that show high regenerative activity suppress the first process while facilitating the second.     

Fibrin/Schwann cell matrix in poly-epsilon-caprolactone conduits enhances guided nerve regeneration

The goal of this study was to investigate if a three dimensional matrix, loaded homogeneously with Schwann cells and the neurotrophic factor LIF (leukemia inhibitory factor), enhances regeneration in a biodegradable nerve guidance channel as compared to non-structured cell suspensions. Therefore a 10 mm nerve gap in the buccal branch of the rat's facial nerve was bridged with tubular PCL (poly-epsilon-caprolactone) conduits filled with no matrix, Schwann cells, the three dimensional fibrin/Schwann cell matrix or the fibrin/Schwann cell matrix added with LIF Four weeks after the nerve defects were bridged histological and morphometric analyses of the implants were performed. In conclusion, the three dimensional fibrin/Schwann cells matrix enhanced the quantity and the quality of peripheral nerve regeneration through PCL conduits. The application of LIF prevented hyperneurotization. Therefore, tissue engineered fibrin/Schwann cells matrices are new invented biocompatible and biodegradable devices for enhancing peripheral nerve regeneration as compared to non-structured cell suspensions without neurotrophic factors.