Production of Scaffolds Using Melt Electrospinning Writing and Cell Seeding.

Melt electrospinning writing (MEW) is a solvent-free fabrication method for making polymer fiber scaffolds with features which include large surface area, high porosity, and controlled deposition of the fibers. These scaffolds are ideal for tissue engineering applications. Here we describe how to produce scaffolds made from poly(ε-caprolactone) using MEW and the seeding of primary human-derived dermal fibroblasts to create cell-scaffold constructs. The same methodology could be used with any number of cell types and MEW scaffold designs.

3D Bioprinting of Complex, Cell-laden Alginate Constructs.

Biofabrication has been receiving a great deal of attention in tissue engineering and regenerative medicine either by manual or automated processes. Different automated biofabrication techniques have been used to produce cell-laden alginate hydrogel structures, especially bioprinting approaches. These approaches have been limited to 2D or simple 3D structures, however. In this chapter, a novel bioprinting technique is disclosed for the production of more complex alginate hydrogel structures. This was achieved by dividing the alginate hydrogel cross-linking process into three stages: primary calcium ion cross-linking for printability of the gel, secondary calcium ion cross-linking for rigidity of the alginate hydrogel immediately after printing, and tertiary barium ion cross-linking for the long-term stability of the alginate hydrogel in the culture medium.

Surface Tension-Assisted Additive Manufacturing of Tubular, Multicomponent Biomaterials.

The fabrication of functional biomaterials for organ replacement and tissue repair remains a major goal of biomedical engineering. Advances in additive manufacturing (AM) technologies and computer-aided design (CAD) are advancing the tools available for the production of these devices. Ideally, these constructs should be matched to the geometry and mechanical properties of the tissue at the needed implant site. To generate geometrically defined and structurally supported multicomponent and cell-laden biomaterials, we have developed a method to integrate hydrogels with 3D-printed lattice scaffolds leveraging surface tension-assisted AM.

Bioprinting of Complex Vascularized Tissues.

Functional vasculature is crucial for the maintenance of living tissues via the transport of oxygen, nutrients, and metabolic waste products. As a result, insufficient vascularization in thick engineered tissues will lead to cell death and necrosis due to mass transport and diffusional constraints. To circumvent these limitations, we describe the development of a microscale continuous optical bioprinting (µCOB) platform for 3D printing complex vascularized tissues with superior resolution and speed. By using the µCOB system, endothelial cells and other supportive cells can be printed directly into hydrogels with precisely controlled distribution and subsequent formation of lumen-like structures in vitro.

Effects of oxygen generating scaffolds on cell survival and functional recovery following acute spinal cord injury in rats.

Persistent local oxygen delivery is crucial to create a microenvironment for cell survival and nerve regeneration in acute spinal cord injury (SCI). This study aimed to fabricate calcium peroxide-based microspheres incorporated into a 3-D construct scaffold as a novel oxygen release therapy for SCI. The scaffolds were able to generate oxygen over the course of 21 days when incubated under hypoxic conditions. In vitro, GFP-labeled bone marrow-derived mesenchymal stem cells (MSCs) were planted into the scaffolds. We observed that scaffolds could enhance MSC survival under hypoxic conditions for more than 21 days. Oxygen generating scaffolds were transplanted into spinal cord injury sites of rats in vivo. Twelve weeks following transplantation, cavity areas in the injury/graft site were significantly reduced due to tissue regeneration. Additionally, the oxygen generating scaffolds improved revascularization as observed through vWF immunostaining. A striking feature was the occurrence of nerve fiber regeneration in the lesion sites, which eventually led to significant locomotion recovery. The present results indicate that the oxygen generating scaffolds have the property of sustained local oxygen release, thus facilitating regeneration in injured spinal cords.

Surface Design of Antifouling Vascular Constructs Bearing Biofunctional Peptides for Tissue Regeneration Applications.

Antifouling polymer layers containing extracellular matrix-derived peptide motifs offer promising new options for biomimetic surface engineering. In this contribution, we report the design of antifouling vascular grafts bearing biofunctional peptide motifs for tissue regeneration applications based on hierarchical polymer brushes. Hierarchical diblock poly(methyl ether oligo(ethylene glycol) methacrylate-block-glycidyl methacrylate) brushes bearing azide groups (poly(MeOEGMA-block-GMA-N3)) were grown by surface-initiated atom transfer radical polymerization (SI-ATRP) and functionalized with biomimetic RGD peptide sequences. Varying the conditions of copper-catalyzed alkyne-azide "click" reaction allowed for the immobilization of RGD peptides in a wide surface concentration range. The synthesized hierarchical polymer brushes bearing peptide motifs were characterized in detail using various surface sensitive physicochemical methods. The hierarchical brushes presenting the RGD sequences provided excellent cell adhesion properties and at the same time remained resistant to fouling from blood plasma. The synthesis of anti-fouling hierarchical brushes bearing 1.2 × 103 nmol/cm2 RGD biomimetic sequences has been adapted for the surface modification of commercially available grafts of woven polyethylene terephthalate (PET) fibers. The fiber mesh was endowed with polymerization initiator groups via aminolysis and acylation reactions optimized for the material. The obtained bioactive antifouling vascular grafts promoted the specific adhesion and growth of endothelial cells, thus providing a potential avenue for endothelialization of artificial conduits.

Integration of Islet/Beta-Cell Transplants with Host Tissue Using Biomaterial Platforms.

Cell-based therapies are emerging for type I diabetes mellitus (T1D), an autoimmune disease characterized by the destruction of insulin-producing pancreatic ß-cells, as a means to provide long-term restoration of glycemic control. Biomaterial scaffolds provide an opportunity to enhance the manufacturing and transplantation of islets or stem cell-derived ß-cells. In contrast to encapsulation strategies that prevent host contact with the graft, recent approaches aim to integrate the transplant with the host to facilitate glucose sensing and insulin distribution, while also needing to modulate the immune response. Scaffolds can provide a supportive niche for cells either during the manufacturing process or following transplantation at extrahepatic sites. Scaffolds are being functionalized to deliver oxygen, angiogenic, anti-inflammatory, or trophic factors, and may facilitate cotransplantation of cells that can enhance engraftment or modulate immune responses. This local engineering of the transplant environment can complement systemic approaches for maximizing ß-cell function or modulating immune responses leading to rejection. This review discusses the various scaffold platforms and design parameters that have been identified for the manufacture of human pluripotent stem cell-derived ß-cells, and the transplantation of islets/ß-cells to maintain normal blood glucose levels.

The effect of macrophages on an atmospheric pressure plasma-treated titanium membrane with bone marrow stem cells in a model of guided bone regeneration.

Guided bone regeneration (GBR) is an established treatment. However, the mechanisms of GBR are not fully understood. Recently, a GBR membrane was identified that acts as a passive barrier to regenerate bone via activation and migration of macrophages (Mps) and bone marrow stem cells (BMSCs). Atmospheric pressure plasma treatment of the titanium membrane (APP-Ti) activated macrophages. The purpose of this study was to analyze whether macrophages attached to an APP-Ti membrane affected differentiation of BMSCs in a GBR model. Human THP-1 macrophages (hMps) were cultured on non-treated Ti (N-Ti) and APP-Ti membrane. Macrophage polarization was analyzed by RT-PCR and immunocytochemistry. Secreted proteins from hMps on N-Ti and APP-Ti were detected by LC/MS/MS. hBMSCs were co-cultured with hMps on N-Ti or APP-Ti and analyzed by osteogenic differentiation, Alizarin red S staining, and alkaline phosphatase (ALP) activity. N-Ti and APP-Ti membrane were also implanted into bone defects of rat calvaria. hMps on APP-Ti were polarized M2-like macrophages. hMps on N-Ti secreted plasminogen activator inhibitor-1 and syndecan-2, but hMps on APP-Ti did not. hBMSCs co-cultured with hMps on APP-Ti increased cell migration and gene expression of osteogenic markers, but suppressed mineralization, while ALP activity was similar to that of hMps on N-Ti in vitro. The volume of newly formed bone was not significantly different between N-Ti and APP-Ti membrane in vivo. M2 polarized hMps on APP-Ti suppressed osteogenic induction of hBMSCs in vitro. The indirect role of hMps on APP-Ti in newly formed bone was limited.

Tantalum-coated polylactic acid fibrous membranes for guided bone regeneration.

Guided bone regeneration (GBR) membrane is necessary to reconstruct the defect bone tissue by defending penetration of soft tissues. Polylactic acid (PLA) attracts much attention to utilize as a GBR membrane because it has relatively high mechanical strength and biodegradability. However, the poor osteoconductivity of PLA is a major concern. The aim of this study is to improve the osteoconductivity of fibrous, electrospun, PLA guided bone regeneration membranes by coating the fiber surface with highly biocompatible tantalum (Ta). Ta coating of electrospun PLA membrane was created through sputtered Ta ions surrounding the PLA fibers. The Ta-coated PLA (Ta-PLA) membranes remain a randomly aligned fibrous structure with no defects caused by sputtering. The chemical composition of Ta-PLA membrane indicates Ta coating was well deposited on PLA fibers. Although the mechanical strength of Ta-PLA was reduced compared with bare PLA membrane, the Ta coating layer does not readily delaminate from the single PLA fiber surface due to its cladded structure which indicates that the Ta coating has high mechanical stability on PLA fibers. In vitro cell tests demonstrate that the attachment, proliferation, and differentiation of preosteoblasts are significantly promoted on the Ta-PLA membranes compared to bare PLA. In an in vivo animal test, most calvarial defects in the Ta-PLA group are covered with newly formed bone within six weeks, while the defects in the bare PLA group are rarely covered. Furthermore, the degree of bone healing in the Ta-PLA group is comparable to healing observed on collagen membranes, which are highly bioactive materials. These results indicate the superior osteoconductivity of Ta-PLA will make it particularly useful as a guided bone regeneration membrane.

Rotary-jet spun polycaprolactone/nano-hydroxyapatite scaffolds modified by simulated body fluid influenced the flexural mode of the neoformed bone.

Polycaprolactone (PCL) is a biocompatible, biodegradable synthetic polymer which in combination with nanohydroxyapatite (nHAp) can give rise to a low cost, nontoxic bioactive product with excellent mechanical properties and slow degradation. Here we produced, characterized and evaluated in vivo the bone formation of PCL/nHAp scaffolds produced by the rotary jet spinning technique. The scaffolds produced were firstly soaked into simulated body fluid for 21 days to also obtain nHAp onto PCL/nHAp scaffolds. Afterwards, the scaffolds were characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy and Raman spectroscopy. For in vivo experiments, 20 male Wistar rats were used and randomly divided in 4 experimental groups (n = 5). A critical defect of 3 mm in diameter was made in the tibia of the animals, which were filled with G1 control (clot); G2-PCL scaffold; G3-PCL/nHAp (5%) scaffold; G4-PCL/nHAp (20%) scaffold. All animals were euthanized 60 days after surgery, and the bone repair in the right tibiae were evaluated by radiographic analysis, histological analysis and histomorphometric analysis. While in the left tibias, the areas of bone repair were submitted to the flexural strength test. Radiographic and histomorphometric analyses no showed statistical difference in new bone formation between the groups, but in the three-point flexural tests, the PCL/nHAp (20%) scaffold positively influenced the flexural mode of the neoformed bone. These findings indicate that PCL/nHAp (20%) scaffold improve biomechanical properties of neoformed bone and could be used for bone medicine regenerative.

Functionalized nerve conduits for peripheral nerve regeneration: A literature review.

Functionalized neurotube are a third-generation of conduits with chemical or architectural bioactivity developed for axonal proliferation. The goal of this review is to provide a synopsis of the functionalized nerve conduits described in the literature according to their chemical and architectural properties and answer two questions: what are their mechanisms of action? Has their efficacy been proven compared to the autologous nerve graft? Our literature review relates all kind of conduits corresponding to functionalized neurotubes in peripheral nerve regeneration found in Medline and PubMed Central. Studies developing nerve gaps, chemotactic or structural features promoting each conduit, results, efficiency were selected. Fifty-five studies were selected and classified in: (a) intraluminal neurotrophic factors; (b) cell-based therapy (combined-in-vein muscles, amniotic membrane, Schwann cells, stem cells); (c) extracellular matrix proteins; (d) tissue engineering; (e) bioimplants. Functionalized neurotubes showed significantly better functional results than after end-to-end nerve suture. No studies can be able to show that neurotube results were better than autologous nerve graft results. We included all studies regardless of effectives to evaluate quality of reinnervation with modern tubulization. Functionalized neurotubes promote basic conduits for peripheral nerve regeneration. Thanks to bioengineering and microsurgery improvement, further neurotubes could promote best level of regeneration and functional recovery to successfully bridge a critical nerve gap.

The CCL2/CCR2 axis is critical to recruiting macrophages into acellular nerve allograft bridging a nerve gap to promote angiogenesis and regeneration.

Acellular nerve allografts (ANAs) are increasingly used to repair nerve gaps following injuries. However, these nerve scaffolds have yet to surpass the regenerative capabilities of cellular nerve autografts; improved understanding of their regenerative mechanisms could improve design. Due to their acellular nature, both angiogenesis and diverse cell recruitment is necessary to repopulate these scaffolds to promote functional regeneration. We determined the contribution of angiogenesis to initial cellular repopulation of ANAs used to repair nerve gaps, as well as the signaling that drives a significant portion of this angiogenesis. Wild-type (WT) mice with nerve gaps repaired using ANAs that were treated with an inhibitor of VEGF receptor signaling severely impaired angiogenesis within ANAs, as well as hampered cell repopulation and axon extension into ANAs. Similarly, systemic depletion of hematogenous-derived macrophages, but not neutrophils, in these mice models severely impeded angiogenesis and subsequent nerve regeneration across ANAs suggesting hematogenous-derived macrophages were major contributors to angiogenesis within ANAs. This finding was reinforced using CCR2 knockout (KO) models. As macrophages represented the majority of CCR2 expressing cells, a CCR2 deficiency impaired angiogenesis and subsequent nerve regeneration across ANAs. Furthermore, an essential role for CCL2 during nerve regeneration across ANAs was identified, as nerves repaired using ANAs had reduced angiogenesis and subsequent nerve regeneration in CCL2 KO vs WT mice. Our data demonstrate the CCL2/CCR2 axis is important for macrophage recruitment, which promotes angiogenesis, cell repopulation, and subsequent nerve regeneration and recovery across ANAs used to repair nerve gaps.

Repair of temporal branch of the facial nerve with novel polyglycolic acid-collagen tube: a case report of two cases.

Autologous nerve transplantation has been the gold standard in the treatment of facial nerve injury, however it has not been achieved satisfactory result and needs donor sacrifice. A polyglycolic acid collagen conduit (Nerbridge, Toyobo Co., Japan) has the potential to compare to or exceed autologous nerve grafts in promoting nerve regeneration. Here we report two cases of traumatic temporal facial nerve injury repairs with Nerbridge. The severed temporal branch of the facial nerve was repaired with Nerbridge conduits in two patients. Recovery of movement was assessed by clinical photography and needle electromyography. The frontal muscle started moving five months postoperatively in both cases. Electromyography at twelve months showed polymorphic electric discharge, suggesting connection of the injured nerve to the frontal muscle. In the final results, each patient had good eyebrow elevation distance and moderate forward gaze recovery in comparison to their healthy sides. Considering that facial nerves are reported to recover incompletely even in autologous nerve graft repair cases, our two cases showed reasonable recovery comparable to nerve autografting. The Nerbridge conduit is a promising alternative to standard treatments for facial nerve recovery.

Fabrication and transplantation of chitosan-selenium biodegradable nanocomposite conduit on transected sciatic nerve: a novel study in rat model.

Purpose: The improvement of techniques using conduits that connects the ends of damaged nerves and guides the growth of nerve fibers between the stumps, including adoption of natural or synthetic materials still is a challenge in peripheral nerve repair. The aim of the present novel study was to fabricate and transplant chitosan-selenium biodegradable nanocomposite conduit on transected sciatic nerve in rat model.Methods: In NORMAL group, the left sciatic nerve was exposed through a gluteal muscle incision and after careful hemostasis skin was closed. In TRANSECTED group left sciatic nerve was transected and stumps were fixed in adjacent muscle. In CHITOSAN and CSBNC groups, 10-mm sciatic nerve defects were bridged using a chitosan and chitosan-selenium biodegradable nanocomposite conduits, respectively. The regenerated fibers were studied 4, 8 and 12 weeks after surgery. Assessment of nerve regeneration was based on behavioral, functional, biomechanical, histomorphometric and immunohistochemical criteria.Results: The behavioral, functional and biomechanical studies confirmed significant recovery of regenerated axons in CSBNC group (P < 0.05). Quantitative morphometric analyses of regenerated fibers showed the number and diameter of myelinated fibers in CSBNC group were significantly higher than in the CHITOSAN group (P < 0.05).Discussion: This demonstrates the potential of using CSBNC in peripheral nerve regeneration without limitations of donor-site morbidity associated with isolation autograft. It is also cost saving and may have clinical implications for the surgical management of patients after facial nerve transection.

Repair strategies for traumatic spinal cord injury, with special emphasis on novel biomaterial-based approaches.

As a part of the central nervous system (CNS), the adult mammalian spinal cord displays only very poor ability for self-repair in response to traumatic lesions, which mostly lead to more or less severe, life-long disability. While even adult CNS neurons have a certain plastic potential, their intrinsic regenerative capacity highly varies among different neuronal populations and in the end, regeneration is almost completely inhibited due to extrinsic factors such as glial scar and cystic cavity formation, excessive and persistent inflammation, presence of various inhibitory molecules, and absence of trophic support and of a growth-supportive extracellular matrix structure. In recent years, a number of experimental animal models have been developed to overcome these obstacles. Since all those studies based on a single approach have yielded only relatively modest functional recovery, it is now consensus that different therapeutic approaches will have to be combined to synergistically overcome the multiple barriers to CNS regeneration, especially in humans. In this review, we particularly emphasize the hope raised by the development of novel, implantable biomaterials that should favor the reconstruction of the damaged nervous tissue, and ultimately allow for functional recovery of sensorimotor functions. Since human spinal cord injury pathology depends on the vertebral level and the severity of the traumatic impact, and since the timing of application of the different therapeutic approaches appears very important, we argue that every case will necessitate individual evaluation, and specific adaptation of therapeutic strategies.

Surface-Anchored Graphene Oxide Nanosheets on Cell-Scale Micropatterned Poly(d,l-lactide-co-caprolactone) Conduits Promote Peripheral Nerve Regeneration.

Regeneration and functional recovery of peripheral nerves remain formidable due to the inefficient physical and chemical cues in the available nerve guidance conduits (NGCs). Introducing micropatterns and bioactive substances into the inner wall of NGCs can effectively regulate the behavior of Schwann cells, the elongation of axons, and the phenotype of macrophages, thereby aiding the regeneration of injured nerve. In this study, linear micropatterns with ridges and grooves of 3/3, 5/5, 10/10, and 30/30 µm were created on poly(d,l-lactide-co-caprolactone) (PLCL) films following with surface aminolysis and electrostatic adsorption of graphene oxide (GO) nanosheets. The GO-modified micropatterns could significantly accelerate the collective migration of Schwann cells (SCs) and migration of SCs from their spheroids in vitro. Moreover, the SCs migrated directionally along the stripes with a fastest rate on the 3/3-GO film that had the largest cell adhesion force. The neurites of N2a cells were oriented along the micropatterns, and the macrophages tended to differentiate into the M2 type on the 3/3-GO film judged by the higher expression of Arg 1 and IL-10. The systematic histological and functional assessments of the regenerated nerves at 4 and 8 weeks post-surgery in vivo confirmed that the 3/3-GO NGCs had better performance to promote the nerve regeneration, and the CMAP, NCV, wet weight of gastrocnemius muscle, positive S100ß and NF200 area percentages, and average myelinated axon diameter were more close to those of the autograft group at 8 weeks. This type of NGCs thus has a great potential for nerve regeneration.

Dextran-based tube-guides for the regeneration of the rat sciatic nerve after neurotmesis injury.

In this work, dextran-based nerve tube-guides were prepared, characterized and used in a standardized animal model of neurotmesis injury. Non-porous and porous transparent tube-guides were obtained by photocrosslinking of two co-macromonomers based on dextran and poly(ε-caprolactone) (PCL). Swelling capacity of the tube-guides ranged from 40-60% with no visible constriction of their inner diameter. In vitro hydrolytic degradation tests showed that the tube-guides maintained their structural integrity up to 6 months. The in vivo performance of the tube-guides was evaluated by entubulation of the rat sciatic nerve after a neurotmesis injury, with a 10 mm-gap between the nerve stumps. The results showed that the tube-guides were able to promote the regeneration of the nerve in a similar manner to what was observed with conventional techniques (nerve graft and end-to-end suture). Stereological analysis proved that nerve regeneration occurred, and both tube-guides presented fibre diameter and g-ratio closer to healthy sciatic nerves. The histomorphometric analysis of Tibialis anterior (TA) skeletal muscle showed decreased neurogenic atrophy in the porous tube-guides treated group, presenting measurements that are similar to the uninjured control.

Bacterial cellulose tubes as a nerve conduit for repairing complete facial nerve transection in a rat model.

PURPOSE: Functionality of the facial nerve is cosmetically important. While many techniques have been investigated, early and effective treatment for traumatic facial nerve paralysis remains challenging. Here, we aim to examine bacterial cellulose (BC) as a new tubularization material for improving facial nerve regeneration. METHODS: Our study was performed on 40 female Sprague Dawley rats. Rats were randomly divided into four groups, with 10 rats per group. In all rats, the main trunk of the facial nerve was completely cut 8 mm before the branching point. For repairing the facial nerve, in group 1, the nerve was left to recover spontaneously (control group); in group 2, it was repaired by primary suturing (8.0 Ethilon sutures, Ethicon); in group 3, BC tubes alone were used to aid nerve repair; and in group 4, both BC tubes and primary sutures (8.0 Ethilon sutures) were used. After 10 weeks, the facial nerve regeneration was evaluated by the whisker movement test and electrophysiologically (nerve stimulation threshold and compound muscle action potential). Nerve regeneration was assessed by calculating the number of myelinated nerve fibers, and by microscopically evaluating the amount of regeneration and fibrosis. RESULTS: No significant difference was observed among the groups in terms of whisker movement and electrophysiological parameters (P > 0.05). We found that the numbers of regenerating myelinated fibers were significantly increased (P < 0.05) when BC tubes were used as a nerve conduit. CONCLUSIONS: BC can be easily shaped into a hollow tube that guides nerve axons, resulting in better nerve regeneration after transection.

Introduction of a novel guided bone regeneration memory shape based device.

Bone regeneration by periosteal distraction has been reported in numerous animal studies; however, the main disadvantages of this technique are poor bone quality and soft tissue invasion in the distracted space. The purpose of this study was to evaluate a novel shape memory-based device to promote bone regeneration in a large, secluded growth space in a rabbit model. Twenty rabbits were divided into two groups. In the first group (n = 10), a device composed of silicone sheets and nitinol strips was inserted subperiosteally in the calvarial area. In the second group (n = 10), only silicone sheets were inserted in the calvarial area. Each group was further divided in half: five animals were sacrificed at 8 weeks postoperatively, and the other five were sacrificed at 16 weeks postoperatively. In the study group, the new device vertically expanded the overlying soft tissue 4 mm above the original bone and created a secluded space; the newly generated bone maximum height median ranged between 2.7 mm in 8 weeks group and 2.6 mm in 16 weeks group. In the control group, a very thin rim of bone was generated below the flat silicone sheets on top of the original bone. Maximum bone heights median ranged from 0.37 mm in 8 weeks group to 0.32 mm in 16 weeks group. The device was proven to be effective at vertically augmenting bone by applying the guided bone regeneration and soft tissue expansion procedures simultaneously. This device may pave the way for a new generation of smart guided bone regeneration membranes that can remember the original dimensions of resorbed bone areas.

Evaluation of dual release of stromal cell-derived factor-1 and basic fibroblast growth factor with nerve conduit for peripheral nerve regeneration: An experimental study in mice.

BACKGROUND: The development of drug delivery systems has enabled the release of multiple bioactive molecules. The efficacy of nerve conduits coated with dual controlled release of stromal cell-derived factor-1 (SDF-1) and basic fibroblast growth factor (bFGF) for peripheral nerve regeneration was investigated. MATERIALS AND METHODS: Sixty-two C57BL6 mice were used for peripheral nerve regeneration with a nerve conduit (inner diameter, 1 mm, and length, 7 mm) and an autograft. The mice were randomized into five groups based on the different repairs of nerve defects. In the group of repair with conduits alone (n = 9), a 5-mm sciatic nerve defect was repaired by the nerve conduit. In the group of repair with conduits coated with bFGF (n = 10), SDF-1 (n = 10), and SDF-1/bFGF (n = 10), it was repaired by the nerve conduit with bFGF gelatin, SDF-1 gelatin, and SDF-1/bFGF gelatin, respectively. In the group of repair with autografts (n = 10), it was repaired by the resected nerve itself. The functional recovery, nerve regeneration, angiogenesis, and TGF-ß1 gene expression were assessed. RESULTS: In the conduits coated with SDF-1/bFGF group, the mean sciatic functional index value (-88.68 ± 10.64, p = .034) and the axon number (218.8 ± 111.1, p = .049) were significantly higher than the conduit alone group, followed by the autograft group; in addition, numerous CD34-positive cells and micro vessels were observed. TGF-ß1 gene expression relative values in the conduits with SDF-1/bFGF group at 3 days (7.99 ± 5.14, p = .049) significantly increased more than the conduits alone group. CONCLUSION: Nerve conduits coated with dual controlled release of SDF-1 and bFGF promoted peripheral nerve regeneration.