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Peripheral nerve injury (PNI) poses a significant public health issue, often leading to muscle atrophy and persistent neuropathic pain, which can drastically impact the quality of life for patients. Electrical stimulation represents an effective and non-pharmacological treatment to promote nerve regeneration. Yet, the postoperative application of electrical stimulation remains a challenge. Here, we propose a fully biodegradable, self-powered nerve guidance conduit (NGC) based on dissolvable zinc-molybdenum batteries. The conduit can offer topographic guidance for nerve regeneration and deliver sustained electrical cues between both ends of a transected nerve stump, extending beyond the surgical window. Schwann cell proliferation and adenosine triphosphate (ATP) production are enhanced by the introduction of the zinc-molybdenum batteries. In rodent models with 10-mm sciatic nerve damage, the device effectively enhances nerve regeneration and motor function recovery. This study offers innovative strategies for creating biodegradable and electroactive devices that hold important promise to optimize therapeutic outcomes for nerve regeneration., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Repairing larger defects (>5 mm) in peripheral nerve injuries (PNIs) remains a significant challenge when using traditional artificial nerve guidance conduits (NGCs). A novel approach that combines 4D printing technology with poly(L-lactide-co-trimethylene carbonate) (PLATMC) and Ti 3 C 2 T x MXene nanosheets is proposed, thereby imparting shape memory properties to the NGCs. Upon body temperature activation, the printed sheet-like structure can quickly self-roll into a conduit-like structure, enabling optimal wrapping around nerve stumps. This design enhances nerve fixation and simplifies surgical procedures. Moreover, the integration of microchannel expertly crafted through 4D printing, along with the incorporation of MXene nanosheets, introduces electrical conductivity. This feature facilitates the guided and directional migration of nerve cells, rapidly accelerating the healing of the PNI. By leveraging these advanced technologies, the developed NGCs demonstrate remarkable potential in promoting peripheral nerve regeneration, leading to substantial improvements in muscle morphology and restored sciatic nerve function, comparable to outcomes achieved through autogenous nerve transplantation., (© 2024 Wiley‐VCH GmbH.)

Objectives: Guided bone regeneration (GBR) is a core procedure used to regenerate bone defects. The aim of the study was to investigate the adherence of Candida albicans on six commercially available polytetrafluoroethylene (PTFE) membranes used in GBR procedures and the subsequent clinical consequences., Materials and Methods: Six commercially available PTFE membranes were tested. Two of the membranes had a textured surface and the other four a plane, nontextured one. C. albicans (ATCC 24433) was cultured for 24 h, and its cell surface hydrophobicity was assessed using a modified method. C. albicans adhesion to membrane discs was studied by scanning electron microscopy (SEM) and real-time polymerase chain reaction (PCR)., Results: C. albicans was found to be hydrophobic (77.25%). SEM analysis showed that C. albicans adherence to all membranes examined was characterized by patchy, scattered, and small clustered patterns except for one nontextured membrane with a most rough surface in which a thick biofilm was observed. Real-time PCR quantification revealed significantly greater adhesion of C. albicans cells to PTFE membranes than the control membrane (p ≤ .001) with the membranes having a textured surface exhibiting the highest count of 2680 × 10 4 cells/ml compared to the count of 707 × 10 4  cells/mL on those with a nontextured one (p ≤ .001). One membrane with nontextured surface, but with most rough surface was found to exhibit the highest count of 3010 × 10 4 cells/ml (p ≤ .05)., Conclusion: The results of this study indicate that C. albicans adhesion on membranes' surfaces depends on the degree of surface roughness and/or on the presence of a texture. Textured PTFE membranes and/or membranes high roughness showed significantly more adhered C. albicans cells. These findings can impact the surgeon's choice of GBR membrane and postoperative maintenance., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Three-dimensional (3D) printing is an emerging tool for creating patient-specific tissue constructs analogous to the native tissue microarchitecture. In this study, anatomically equivalent 3D nerve conduits were developed using thermoplastic polyurethane (TPU) by combining reverse engineering and material extrusion (i.e. fused deposition modeling) technique. Printing parameters were optimized to fabricate nerve-equivalent TPU constructs. The TPU constructs printed with different infill densities supported the adhesion, proliferation, and gene expression of neuronal cells. Subcutaneous implantation of the TPU constructs for three months in rats showed neovascularization with negligible local tissue inflammatory reactions and was classified as a non-irritant biomaterial as per ISO 10993-6. To perform in vivo efficacy studies, nerve conduits equivalent to rat's sciatic nerve were fabricated and bridged in a 10 mm sciatic nerve transection model. After four months of implantation, the sensorimotor function and histological assessments revealed that the 3D printed TPU conduits promoted the regeneration in critical-sized peripheral nerve defects equivalent to autografts. This study proved that TPU-based 3D printed nerve guidance conduits can be created to replicate the complicated features of natural nerves that can promote the regeneration of peripheral nerve defects and also show the potential to be extended to several other tissues for regenerative medicine applications., (© 2024 IOP Publishing Ltd.)

Peripheral nerve injury (PNI) represents a serious clinical and public health problem due to its high incurrence and poor spontaneous recovery. Compared to autograft, which is still the best current practice for long-gap peripheral nerve defects in clinics, the use of polymer-based biodegradable nerve guidance conduits (NGCs) has been gaining momentum as an alternative to guide the repair of severe PNI without the need of secondary surgery and donor nerve tissue. However, simple hollow cylindrical tubes can barely outperform autograft in terms of the regenerative efficiency especially in critical sized PNI. With the rapid development of tissue engineering technology and materials science, various functionalized NGCs have emerged to enhance nerve regeneration over the past decades. From the aspect of scaffold design considerations, with a specific focus on biodegradable polymers, this review aims to summarize the recent advances in NGCs by addressing the onerous demands of biomaterial selections, structural designs, and manufacturing techniques that contributes to the biocompatibility, degradation rate, mechanical properties, drug encapsulation and release efficiency, immunomodulation, angiogenesis, and the overall nerve regeneration potential of NGCs. In addition, several commercially available NGCs along with their regulation pathways and clinical applications are compared and discussed. Lastly, we discuss the current challenges and future directions attempting to provide inspiration for the future design of ideal NGCs that can completely cure long-gap peripheral nerve defects., (© 2024 IOP Publishing Ltd.)

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.

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.

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.

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.

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.

Cell-based therapies are emerging for type I diabetes mellitus (T1D), an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-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 β-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 β-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 β-cells, and the transplantation of islets/β-cells to maintain normal blood glucose levels., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2020. Published by Elsevier Masson SAS.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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-N 3 )) 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 × 10 3 nmol/cm 2 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.

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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.

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.

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., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

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-β1 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-β1 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., (© 2019 Wiley Periodicals, Inc.)

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 S100β 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.

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.

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., (© 2019 Wiley Periodicals, Inc.)

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.

Peripheral nerve regeneration remains a challenge in tissue engineering and regenerative medicine. However, the existing approaches have limited regenerative capability. 3D-printed nerve conduits with well-defined properties are potent tools to facilitate peripheral nerve regeneration after injuries. Meanwhile, the vascular networks within the constructs can promote the exchange of oxygen, neurotrophic factors, and removal of waste products, thereby providing an advantageous microenvironment for tissue regeneration. It will be an interesting approach to integrate 3D-printed nerve conduit with vascular networks for the guidance of regenerated nerves. We hypothesize that 3D-printed vascularized nerve conduit will be an effective platform to promote nerve regeneration and functional restoration., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A novel tri-layered, functionally-graded chitosan membrane (FGM) with bioactive glass gradient (50%, 25%, and 0% wt.) was developed by lyophilization. A step-wise grading of chitosan, bioactive glass (BG), and Pluronic F127 was introduced into the membrane in which each layer has separate surface functions that play a role of guided tissue regeneration (GTR) membranes. The lower layer was designed to replicate alveolar bone and contains 50%wt. BG, the middle layer contains 25%wt. BG, while the upper layer was non-porous without BG and it did not support cell growth. Scanning Electron Microscopy (SEM) revealed that the lower FGM surface possessed a porous structure with embedded BG particles, while the upper surface was non-porous with interconnected architecture. The contact angle measurement confirmed that the surface with BG was hydrophilic (≈0 0 ), while the opposite surface was hydrophobic (91 0  ± 3.84 0 ). Both osteoblast and fibroblast cells have maximum adhesion at contact angle <80°. Alamar blue assay revealed the biocompatibility of the MC3T3-E1 mouse pre-osteoblasts cells with these membranes in vitro. The cells attachment and proliferation was seen for lower surface, while no cells adhesion was observed for the upper layer. Additionally, the interaction of the tissue with these tri-layered membranes was also investigated in vivo. Hematoxylin and eosin staining revealed the biocompatible nature of these membranes. Altogether, these results indicated that due to the biocompatible nature of these membranes, they will be a good carrier of in vivo implantation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Dysfunction of the corneal endothelium (CE) resulting from progressive cell loss leads to corneal oedema and significant visual impairment. Current treatments rely upon donor allogeneic tissue to replace the damaged CE. A donor cornea shortage necessitates the development of biomaterials, enabling in vitro expansion of corneal endothelial cells (CECs). This study investigated the use of a synthetic peptide hydrogel using poly-ε-lysine (pεK), cross-linked with octanedioic-acid as a potential substrate for CECs expansion and CE grafts. PεK hydrogel properties were optimised to produce a substrate which was thin, transparent, porous and robust. A human corneal endothelial cell line (HCEC-12) attached and grew on pεK hydrogels as confluent monolayers after 7 days, whereas primary porcine CECs (pCECs) detached from the pεK hydrogel. Pre-adsorption of collagen I, collagen IV and fibronectin to the pεK hydrogel increased pCEC adhesion at 24 h and confluent monolayers formed at 7 days. Minimal cell adhesion was observed with pre-adsorbed laminin, chondroitin sulphate or commercial FNC coating mix (fibronectin, collagen and albumin). Functionalisation of the pεK hydrogel with synthetic cell binding peptide H-Gly-Gly-Arg-Gly-Asp-Gly-Gly-OH (RGD) or α2β1 integrin recognition sequence H-Asp-Gly-Glu-Ala-OH (DGEA) resulted in enhanced pCEC adhesion with the RGD peptide only. pCECs grown in culture at 5 weeks on RGD pεK hydrogels showed zonula occludins 1 staining for tight junctions and expression of sodium-potassium adenosine triphosphase, suggesting a functional CE. These results demonstrate the pεK hydrogel can be tailored through covalent binding of RGD to provide a surface for CEC attachment and growth. Thus, providing a synthetic substrate with a therapeutic application for the expansion of allogenic CECs and replacement of damaged CE.

Barrier membranes are essential biomaterials for guided bone regeneration. Due to different origin and structure of barrier membranes, singular mechanical properties and clinical behaviors can be expected. It is important to understand the physic and chemical properties of barrier membranes to select the needed biomaterial for each clinical situation. To date, no study has evaluated and compared the physicochemical properties of various families of barrier membranes. The aim of this study is to evaluate the physicochemical properties of various barrier membranes. Fifteen membranes of different origin were tested in this study. Membranes were divided into biological or synthetic origin and grouped in natural allogenic collagen, natural xenogenic collagen, cross-linked collagen and synthetic membranes. Physicochemical properties were evaluated in terms of tension, stiffness, absorption ability, pH and wettability. For the tension tests, all membranes showed similar low tension and low stiffness, especially after a 4-min hydration, except for bone laminas that showed a greater stiffness particularly in a dry status. Regarding wettability and hydration of the barrier membranes, porcine origin membranes had greater hydration; wettability was also superior in porcine derived barrier membranes and showed a faster absorption of the drop on the rough surfaces. All membranes had a stable pH, having the synthetic membranes the most stable pH when compared to physiologic. The wide variety of barrier membranes opens a debate in which the practitioner should select the adequate barrier membrane for each clinical situation. Different materials show singular potentials depending on their tissue origin making them suitable for specific clinical indications. More studies regarding adsorption, integration and degradation of barrier membranes are needed to understand their behavior., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Heart valves are characterized to be highly flexible yet tough, and exhibit complex deformation characteristics such as nonlinearity, anisotropy, and viscoelasticity, which are, at best, only partially recapitulated in scaffolds for heart valve tissue engineering (HVTE). These biomechanical features are dictated by the structural properties and microarchitecture of the major tissue constituents, in particular collagen fibers. In this study, the unique capabilities of melt electrowriting (MEW) are exploited to create functional scaffolds with highly controlled fibrous microarchitectures mimicking the wavy nature of the collagen fibers and their load-dependent recruitment. Scaffolds with precisely-defined serpentine architectures reproduce the J-shaped strain stiffening, anisotropic and viscoelastic behavior of native heart valve leaflets, as demonstrated by quasistatic and dynamic mechanical characterization. They also support the growth of human vascular smooth muscle cells seeded both directly or encapsulated in fibrin, and promote the deposition of valvular extracellular matrix components. Finally, proof-of-principle MEW trileaflet valves display excellent acute hydrodynamic performance under aortic physiological conditions in a custom-made flow loop. The convergence of MEW and a biomimetic design approach enables a new paradigm for the manufacturing of scaffolds with highly controlled microarchitectures, biocompatibility, and stringent nonlinear and anisotropic mechanical properties required for HVTE., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Peripheral nerve physiology and regeneration has been observed and investigated in literature but surgical applications to reconstruct and restore motor or sensory functions are still in a developmental phase. The peripheral nerve progresses slowly and incompletely compared with other tissues, it may provoke separations of the nerve stumps and the axonal proliferation of the conduits is restricted to 30 mm. Recent surgical attempts to treat proximal nerve injures include direct nerve restoration, transfer, and autografting measures with favorable results. Moreover, studies are suggesting that engineering tissue tubes maybe as effective as nerve grafting to restore separations of more than 4 cm toward optimal nerve repair., (© 2018 Wiley Periodicals, Inc.)

For cartilage tissue repairing, it remains a key challenge to design implant materials with antibacterial activity, proper degradation rate and mechanical property. In this research, antibacterial nanodiamonds (QND, QND-Ag) modified acrylate-terminated polyurethanes (APU) were prepared. By the addition of nanocomposites, the crystallinity of modified APU obviously increased, which indicates a strong interaction between NDs and APU. Tensile and compression tests were carried out to evaluate the improved mechanical properties. Compared with APU, APU(10%PEG)/QND-Ag possessed the increased modulus and strength, a nevertheless slight decrease in elongation at break. Due to the dual actions of contact-killing of cationic polymers and release-killing of the Ag NPs, QND-Ag-containing polyurethane showed excellent antibacterial activity against Staphylococcus aureus. Moreover, APU containing polyethylene glycol showed a significant increase in degradability rates. Consequently, owing to the dual effect of crystallinity and hydrophilicity, our modified APU exhibited the proper degradation rate adaptable to the healing rate of cartilage tissue. Furthermore, the CCK-8 results demonstrated that synthesized samples were low toxic. Therefore, APU(10%PEG)/QND-Ag holds great promise for the application of cartilage tissue repairing.

The reconstruction of peripheral nerve injuries is clinically challenging, and today, the autologous nerve transplantation is still considered as the only gold standard remedy for nerve lesions where a direct nerve coaptation is not possible. Nevertheless, the functional merits of many biomaterials have been tested as potential substitutes for the autologous nerve transplant. One of the strategies that have been pursued is the combination of bioengineered nerve guides with cellular enrichment. In this present study, we combined the previously evaluated collagen-based and microstructured nerve guide Perimaix with olfactory ensheathing cell enrichment. Rat sciatic nerve defects of 20 mm were either bridged by a cell-seeded or nonseeded nerve guide or an autologous nerve transplant. Animals were monitored for 12 weeks for structural and functional parameters. Seeded cells survived on Perimaix, and following implantation aligned along the microstructured Perimaix framework. Axonal densities within the cell-seeded nerve guides were higher than in the nonseeded nerve guides and were comparable to the autograft. Additionally, cell-seeding had local beneficial effects on myelination within the nerve guide, as myelin sheath thickness was enhanced when compared with the empty scaffold. Nevertheless, for bridging the nerve gap of 20 mm, both the cell-seeded as well as nonseeded scaffolds were equally efficient regarding the functional outcome, which did not differ between the autograft, seeded or nonseeded groups. Our data demonstrate that olfactory ensheathing cell enrichment has local effects on nerve regeneration in combination with the Perimaix nerve guide. Surprisingly, for traversing the lesion gap, additional cell-seeding is not crucial., (© 2018 John Wiley & Sons, Ltd.)

This study reported guided growth for caput valgum deformity and subsequent hip development. Ten children with unilateral hip dysplasia had guided growth by one eccentric transphyseal screw at age 9.1 years with minimum 2 years of follow-up. The first change was decreasing articulotrochanteric distance and then increasing physis tilt angle and head-shaft angle by 1.5 years. The center edge angle that was significantly less than the normal side (18.3 vs. 24.8°) preoperatively became comparable between both the hips 2 years later. Rebounding of physis inclination after screw back out suggested mechanical tethering, rather than permanent physis closure, resulted in morphologic changes in the femur., Level of Evidence: Therapeutic study, level IV.

Carbon-based nanomaterials have shown great promise in regenerative medicine because of their unique electrical, mechanical, and biological properties; however, it is still difficult to engineer 2D pure carbon nanomaterials into a 3D scaffold while maintaining its structural integrity. In the present study, we developed novel carbon nanofibrous scaffolds by annealing electrospun mats at elevated temperature. The resultant scaffold showed a cohesive structure and excellent mechanical flexibility. The graphitic structure generated by annealing renders superior electrical conductivity to the carbon nanofibrous scaffold. By integrating the conductive scaffold with biphasic electrical stimulation, neural stem cell proliferation was promoted associating with upregulated neuronal gene expression level and increased microtubule-associated protein 2 immunofluorescence, demonstrating an improved neuronal differentiation and maturation. The findings suggest that the integration of the conducting carbon nanofibrous scaffold and electrical stimulation may pave a new avenue for neural tissue regeneration., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We used radiological and histological analyses to evaluate the effects of mechanical barrier permeability in a rat model of calvarial guided bone augmentation (GBA). The calvaria of 20 rats were exposed, and one of four types of plastic caps (an occlusive cylindrical plastic cap; a plastic cap with no top; a plastic cap with three holes; and a plastic cap with four holes) was randomly placed on both sides. Newly generated bone in the plastic caps was evaluated with micro-computed tomography (micro-CT) and histological analysis. Micro-CT volumetric analysis and decalcified hematoxylin and eosin-stained sections showed that GBA barrier permeability was inversely associated with the quantity of augmented bone obtained. Masson's trichrome staining showed that collagen in newly generated bony tissue was more mature in plastic caps with three holes than in those with more-permeable or more-occlusive barriers. Bone augmentation was inhibited in specimens exhibiting invasion of soft tissue through penetrating holes, and barrier permeability was associated with the quantity of augmented bone developed. In conclusion, moderate barrier permeability is optimal for development of mature augmented bone.

Background/aim: Lost alveolar bone is commonly restored by distraction osteogenesis or bone blocks for substantial vertical bone augmentation (VBA), that is applied in conjunction with a barrier system. This study was performed to determine whether volume control of a three-dimensional (3D) printed nylon cap in the rat calvarial partial thickness bone defect would induce qualitative and quantitative differences in vertical bone regeneration., Materials and Methods: A rat calvarial partial thickness bone defect was prepared and the 3D cap covered the defect to induce VBA, while the control group was left without cap placement. After six weeks the animals were sacrificed, and the calvaria were prepared for micro-CT (μCT) and histology., Results: Quantitative μCT results showed that our cap system has significant osteoconductive properties, and the histology slide revealed new bone filled inside the cap., Conclusion: The results clearly showed that this system was successful for VBA in a research animal model., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Peripheral sensory nerve injuries present a significant yet common challenge in acute hand trauma surgery. Standard treatment remains microsurgical end-to-end nerve repair where appropriate. Permanent loss of sensitivity and painful neuroma formation are typical sequelae of unsuccessful surgery. The objective of this study was to evaluate whether the additional use of a chitosan nerve tube in primary nerve repair positively influences sensory recovery., Methods: A randomized, controlled, two-center trial with parallel group design and double-blind assessment was conducted to demonstrate the superiority of the additional use of a chitosan nerve tube compared with microsurgical nerve repair alone. Seventy-four participants were enrolled. The primary outcome parameter used was degree of static two-point discrimination at 6 months after surgery. Additional secondary outcome parameters included filament recognition testing (Semmes-Weinstein); pain; neuroma development; and the Disabilities of the Arm, Shoulder and Hand score., Results: Nerve repair with additional use of chitosan nerve tubes (intervention group) significantly increased both tactile gnosis (expressed by two-point discrimination) and sensitivity (expressed by Semmes-Weinstein testing). The mean two-point discrimination at 6-month follow-up was 8 mm (range, 2 to 20 mm) in the control group and 6.3 mm (range, 1 to 15 mm) in the intervention group, respectively (p = 0.029). Two-point discrimination correlated with the Disabilities of the Arm, Shoulder and Hand score. In the control and intervention groups, respectively, three versus zero neuromas were found., Conclusions: Peripheral sensory nerve regeneration can be improved significantly by additional use of a chitosan nerve tube. An improved ability of static two-point discrimination is clinically relevant., Clinical Question/level of Evidence: Therapeutic, I.

Objectives: Materials used in paediatric cardiac surgery have drawbacks of deterioration, calcification and pseudointimal proliferation resulting in haemodynamic disturbance. The aim of this study was to investigate whether these drawbacks can be overcome by in situ tissue regeneration using a newly developed synthetic hybrid fabric (SHF)., Methods: The SHF is an expandable, warp-knitted fabric composed of a combination of biodegradable [poly-l-lactic acid (PLLA)] and non-biodegradable (polyethylene terephthalate) yarns. The fabric is coated with cross-linked gelatin. Mechanical properties of the SHF were compared with those of 2 commercial products: expanded polytetrafluoroethylene sheet and glutaraldehyde-treated bovine pericardium. An oval-shaped defect created in the canine descending aorta or inferior vena cava was filled with the SHF patch. After 2 weeks and 1, 3, 6 and 12 (or 24 in the inferior vena cava) months, the patch was removed for histological examination and evaluation of the remaining PLLA., Results: The SHF exhibited satisfactory tensile and suture retention strength for surgical implantation similar to or better than the 2 commercial products. Tissue regeneration was induced with multilayered smooth muscle cells and collagen fibres on both sides of the patch, along with a mature endothelial layer and tissue connections containing vasa vasorum across the patch in the aorta and inferior vena cava. Inflammatory reactions were minimal, and no calcium deposition occurred. The molecular weight of PLLA was reduced to half at 12 months after implantation., Conclusions: The SHF may solve the drawbacks of the existing products. Further studies of the expandability of the SHF patch after degradation of PLLA are warranted.

Electrically generated cold atmospheric plasma is being intensively researched for novel applications in biology and medicine. Significant attention is being given to reactive oxygen and nitrogen species (RONS), initially generated upon plasma-air interactions, and subsequently delivered to biological systems. Effects of plasma exposure are observed to millimeter depths within tissue. However, the exact nature of the initial plasma-tissue interactions remains unknown, including RONS speciation and delivery depth, or how plasma-derived RONS intervene in biological processes. Herein, we focus on current research using tissue and cell models to learn more about the plasma delivery of RONS into biological environments. We argue that this research is vital in underpinning the knowledge required to realize the full potential of plasma in biology and medicine., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The external auditory canal (EAC) is an osseocartilaginous structure extending from the auricle to the eardrum, which can be affected by congenital, inflammatory, and neoplastic diseases, thus reconstructive materials are needed. Current biomaterial-based approaches for the surgical reconstruction of EAC posterior wall still suffer from resorption (biological) and extrusion (synthetic). In this study, 3D fiber deposited scaffolds based on poly(ethylene oxide terephthalate)/poly(butylene terephthalate) were designed and fabricated to replace the EAC wall. Fiber diameter and scaffold porosity were optimized, leading to 200 ± 33 µm and 55% ± 5%, respectively. The mechanical properties were evaluated, resulting in a Young's modulus of 25.1 ± 7.0 MPa. Finally, the EAC scaffolds were tested in vitro with osteo-differentiated human mesenchymal stromal cells (hMSCs) with different seeding methods to produce homogeneously colonized replacements of interest for otologic surgery. This study demonstrated the fabrication feasibility of EAC wall scaffolds aimed to match several important requirements for biomaterial application to the ear under the Tissue Engineering paradigm, including shape, porosity, surface area, mechanical properties and favorable in vitro interaction with osteoinduced hMSCs. This study demonstrated the fabrication feasibility of outer ear canal wall scaffolds via additive manufacturing. Aimed to match several important requirements for biomaterial application to ear replacements under the Tissue Engineering paradigm, including shape, porosity and pore size, surface area, mechanical properties and favorable in vitro interaction with osteo-differentiated mesenchymal stromal cells.

Objectives: This study examines the permeability and barrier capacity of a sugar cross-linked resorbable collagen membrane ex vivo and in vivo., Materials and Methods: In an ex vivo study, injectable platelet-rich fibrin (i-PRF), a peripheral blood-derived human leukocyte-and-platelet-rich plasma was used to analyze membrane permeability. in vivo subcutaneous implantation in Wistar rats (n = 4 per time point and group) was used to investigate the barrier capacity of the membrane. The induced in vivo cellular reaction was evaluated at 3, 15, and 30 days and compared to sham OP (control) without biomaterial using histological, immunohistochemical, and histomorphometric methods., Results: Ex vivo, the membrane was impenetrable to leukocytes, platelets, and fibrin from peripheral human blood concentrate (PRF). In vivo, the membrane maintained its structure and remained impervious to cells, connective tissue, and vessels over 30 days. CD-68-positive cell (macrophage) numbers significantly decreased from 3 to 15 days, while from day 15 onwards, the number of multinucleated giant cells (MNGCs) increased significantly. Correspondingly, a rise in implantation bed vascularization from 15 to 30 days was observed. However, no signs of degradation or material breakdown were observed at any time point., Conclusion: Ex vivo and in vivo results showed material impermeability to cellular infiltration of human and murine cells, which highlights the membrane capacity to serve as a barrier over 30 days. However, whether the induced MNGCs will lead to material degradation or encapsulation over the long term requires further investigation., Clinical Relevance: The data presented are of great clinical interest, as they contribute to the ongoing discussion concerning to what extent an implanted material should be integrated versus serving only as a barrier membrane.

Background: External volume expansion devices are effective for adipose tissue regeneration. However, the detailed mechanisms by which external volume expansion devices induce adipose tissue regeneration remain unclear., Methods: An external volume expansion device was used to construct expanded prefabricated adipose tissue in a rat model. CXCL12 levels in local exudate and serum were measured by enzyme-linked immunosorbent assay, and CXCL12 expression in adipose tissue was assessed immunohistochemically. Fluorescent dye (CM-DiI)-labeled bone marrow-derived mesenchymal stromal cells and labeled mesenchymal stromal cells pretreated with the CXCR4 antagonist AMD3100 were transplanted into rats and tracked in vivo by fluorescence imaging., Results: CXCL12 levels in local exudate and serum peaked 2 and 7 days, respectively, after external volume expansion device application. CXCL12 cell counts were significantly higher in the external volume expansion than in the control group. These CXCL12 cells were mainly columnar or cuboidal and began to express peroxisome proliferator-activated receptor γ on day 9. CM-DiI-labeled mesenchymal stromal cells were successfully recruited to the expanded prefabricated adipose tissue, a process partly inhibited by the CXCR4 antagonist AMD3100. These recruited CM-DiI-labeled mesenchymal stromal cells were found among the CXCL12 columnar cells., Conclusions: External volume expansion devices enhance CXCL12 expression levels, especially in columnar and cuboidal cells. The CXCL12/CXCR4 pathway is involved in recruiting circulating mesenchymal stromal cells to participate in adipose regeneration. These findings may reveal the mechanism underlying external volume expansion and provide insights into the refinement of these devices.

The aim of the present study was to evaluate the physiochemical properties and resorption progress of two cross-linked, porcine skin-derived collagen membranes and compare their features with those of a membrane without cross-linking (Bio-Gide ® [BG], Geistlich Biomaterials, Wolhusen, Switzerland). Three porcine skin-derived collagen membranes, dehydrothermally (DHT) cross-linked (experimental), DHT and 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide (DHT/EDC) cross-linked (experimental) and BG were investigated for their morphology, enzyme resistance, and tensile strength in vitro and biodegradation in vivo. DHT and DHT/EDC membranes exhibited irregular, interconnected macro- and micropores that formed a 3D mesh, whereas BG exhibited individual collagen fibrils interlaced to form coarse collagen strands. In enzyme resistance and tensile strength tests, DHT and DHT/EDC membranes demonstrated good resistance and mechanical properties compared with BG. In vivo, all three membranes were well integrated into the surrounding connective tissue. Thus, the DHT membrane exhibited its potential as a barrier membrane for guided bone and tissue regeneration.

An agarose scaffold can be useful for supporting and guiding injured axons after spinal cord injury (SCI), but the electrophysiological signal of regenerated axon in scaffolds has not yet been determined. The current study investigated whether a Matrigel-loaded agarose scaffold would enhance the regeneration of axons after SCI. Moreover, the functional connectivity of regenerated axons within the channels of the scaffold was evaluated by directly recording motor evoked potentials. Our data showed that the agarose scaffold containing Matrigel can support and enhance linearly organized axon regeneration after SCI. Additionally, motor evoked potentials were successfully recorded from regenerated axons. These results demonstrate that an agarose scaffold loaded with Matrigel could promote the regeneration of axons and guide the reconnection of functional axons after SCI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Integra® dermal regeneration template is a bilayer membrane system that acts as a scaffold for regenerating dermal skin cells. It is used for wound reconstruction following burns, extensive injuries, and a large tumor excision in multiple parts of the body. The dermal layer is made of porous matrix of bovine tendon collagen and glycosaminoglycan. The epidermal layer is made of polysiloxane layer. In this study, the authors evaluated the use of Integra® dermal regeneration template for the immediate reconstruction of the orbital exenteration socket., Methods: Five patients who underwent exenteration and immediate reconstruction of the socket with Integra® dermal regeneration template were included in this study. Demographic and clinical features, healing time, complications, and follow-up time were recorded., Results: The study included 4 male patients and 1 female patient with a mean age of 74 years (range, 49-87 years). The primary diagnoses were orbital extension of conjunctival melanoma in 2 patients, squamous cell carcinoma in 1 patient, and uveal melanoma in 1 patient, and aggressive orbital Wegener granulomatosis in 1 patient. There was no postoperative infection, necrosis, hematoma, or fluid accumulation in any patients. The mean postoperative follow-up period was 20 months (range, 11-42 months). The sockets were completely granulated by 4 weeks, and epithelized, getting ready for the prosthesis in 8 weeks., Conclusions: Integra® dermal regeneration template can be used for the immediate reconstruction of the socket following exenteration. It is easy to use, and provides a short healing time without any need for any additional reconstructive procedures.

In our previous study, we found that gelatin-based materials exhibit good conductivity and are non-cytotoxic. In this study, gelatin was cross-linked with bisvinyl sulfonemethyl (BVSM) to fabricate a biodegradable conduit for peripheral nerve repair. First, BVSM on the prepared conduit was characterized to determine its mechanical properties and contact angle. The maximum tensile strength and water contact angle of the gelatin-BVSM conduits were 23 ± 4.8 MPa and 74.7 ± 9°, which provided sufficient mechanical strength to resist muscular contraction; additionally, the surface was hydrophilic. Cytotoxicity and apoptosis assays using Schwann cells demonstrated that the gelatin-BVSM conduits are non-cytotoxic. Next, we examined the neuronal electrophysiology, animal behavior, neuronal connectivity, macrophage infiltration, calcitonin gene-related peptide localization and expression, as well as the expression levels of nerve regeneration-related proteins. The number of fluorogold-labelled cells and histological analysis of the gelatin-BVSM nerve conduits was similar to that observed with the clinical use of silicone rubber conduits after 8 weeks of repair. Therefore, our results demonstrate that gelatin-BVSM conduits are promising substrates for application as bioengineered grafts for nerve tissue regeneration.

Introduction: When a nerve section with a significant gap occurs, it is necessary to use a prosthesis to suture it. To date an autologous nerve segment graft appears to be the best treatment; but it has several important disadvantages. Our goal is to study the effectiveness of an isogenic acellular nerve prosthesis comparing a simple suture with tubulisation., Material and Method: Four groups of Wistar rats were used. The animals in Group 0 served as donors of nerve segments to graft. Group 1 received the implant with an end-to-end suture. In group 2, the implant was sutured inside an ɛ-caprolactone tube. Group 3 received it in a polylactic-co-glycolic acid tube. We evaluated the motor function (sciatic index and step test in motion), and the regeneration length by histological study of regeneration, after a maximum of 3 weeks., Results: Regeneration was uneven in the three groups. In all groups, there were implants with regenerated nerve fibres at the maximum studied length (15mm) and others where regeneration was scarce. The mean regeneration length was greater in the direct end-to-end suture group (G1), although the regeneration speed was similar in the three groups. Group 1 showed the highest percentage of regeneration, but the variability of results prevents this difference reaching statistical significance. We found no significant differences between the two groups with polymer tubes., Conclusion: For the implantation of isogenic acellular nerve prosthesis, under our experimental conditions, the direct end-to-end suture was more effective than when it isprotected with biopolymer tubes., (Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

Tendon and ligament (T/L) function is intrinsically related with their unique hierarchically and anisotropically organized extracellular matrix. Their natural healing capacity is, however, limited. Here, continuous and aligned electrospun nanofiber threads (CANT) based on synthetic/natural polymer blends mechanically reinforced with cellulose nanocrystals are produced to replicate the nanoscale collagen fibrils grouped into microscale collagen fibers that compose the native T/L. CANT are then incrementally assembled into 3D hierarchical scaffolds, resulting in woven constructions, which simultaneously mimic T/L nano-to-macro architecture, nanotopography, and nonlinear biomechanical behavior. Biological performance is assessed using human-tendon-derived cells (hTDCs) and human adipose stem cells (hASCs). Scaffolds nanotopography and microstructure induce a high cytoskeleton elongation and anisotropic organization typical of tendon tissues. Moreover, the expression of tendon-related markers (Collagen types I and III, Tenascin-C, and Scleraxis) by both cell types, and the similarities observed on their expression patterns over time suggest that the developed scaffolds not only prevent the phenotypic drift of hTDCs, but also trigger tenogenic differentiation of hASCs. Overall, these results demonstrate a feasible approach for the scalable production of 3D hierarchical scaffolds that exhibit key structural and biomechanical properties, which can be advantageously explored in acellular and cellular T/L TE strategies., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)