Functional tissue-engineered microtissue formed by self-aggregation of cells for peripheral nerve regeneration

Background Peripheral nerve injury (PNI) is one of the essential causes of physical disability with a high incidence rate. The traditional tissue engineering strategy, Top-Down strategy, has some limitations. A new tissue-engineered strategy, Bottom-Up strategy (tissue-engineered microtissue strategy), has emerged and made significant research progress in recent years. However, to the best of our knowledge, microtissues are rarely used in neural tissue engineering; thus, we intended to use microtissues to repair PNI. Methods We used a low-adhesion cell culture plate to construct adipose-derived mesenchymal stem cells (ASCs) into microtissues in vitro, explored the physicochemical properties and microtissues components, compared the expression of cytokines related to nerve regeneration between microtissues and the same amount of two-dimension (2D)-cultured cells, co-cultured directly microtissues with dorsal root ganglion (DRG) or Schwann cells (SCs) to observe the interaction between them using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA). We used grafts constructed by microtissues and polycaprolactone (PCL) nerve conduit to repair sciatic nerve defects in rats. Results The present study results indicated that compared with the same number of 2D-cultured cells, microtissue could secrete more nerve regeneration related cytokines to promote SCs proliferation and axons growth. Moreover, in the direct co-culture system of microtissue and DRG or SCs, axons of DRG grown in the direction of microtissue, and there seems to be a cytoplasmic exchange between SCs and ASCs around microtissue. Furthermore, microtissues could repair sciatic nerve defects in rat models more effectively than traditional 2D-cultured ASCs. Conclusion Tissue-engineered microtissue is an effective strategy for stem cell culture and therapy in nerve tissue engineering.

Recombinant Adenoviruses for Delivery of Therapeutics Following Spinal Cord Injury

The regeneration of nerve tissue after spinal cord injury is a complex and poorly understood process. Medication and surgery are not very effective treatments for patients with spinal cord injuries. Gene therapy is a popular approach for the treatment of such patients. The delivery of therapeutic genes is carried out in a variety of ways, such as direct injection of therapeutic vectors at the site of injury, retrograde delivery of vectors, and ex vivo therapy using various cells. Recombinant adenoviruses are often used as vectors for gene transfer. This review discusses the advantages, limitations and prospects of adenovectors in spinal cord injury therapy.

Application of Hybrid Electrically Conductive Hydrogels Promotes Peripheral Nerve Regeneration

Peripheral nerve injury (PNI) occurs frequently, and the prognosis is unsatisfactory. As the gold standard of treatment, autologous nerve grafting has several disadvantages, such as lack of donors and complications. The use of functional biomaterials to simulate the natural microenvironment of the nervous system and the combination of different biomaterials are considered to be encouraging alternative methods for effective tissue regeneration and functional restoration of injured nerves. Considering the inherent presence of an electric field in the nervous system, electrically conductive biomaterials have been used to promote nerve regeneration. Due to their singular physical properties, hydrogels can provide a three-dimensional hydrated network that can be integrated into diverse sizes and shapes and stimulate the natural functions of nerve tissue. Therefore, conductive hydrogels have become the most effective biological material to simulate human nervous tissue’s biological and electrical characteristics. The principal merits of conductive hydrogels include their physical properties and their electrical peculiarities sufficient to effectively transmit electrical signals to cells. This review summarizes the recent applications of conductive hydrogels to enhance peripheral nerve regeneration.

Spectral analyses of fresh and dry Hypericum perforatum L. Effects with colloidal nano silver 30 ppm

Spectral analyses of 1% water extracts of fresh and dry Hypericum perforatum L. and 1% dry H. perforatum with colloidal nano silver (NSPs) 30 ppm were conducted. The nano silver is standardised and patented by the Swiss company Evodrop. Non-equliblrium energy spectrum (NES) and Differential non-equliblrium energy spectrum (DNES) methods were used for the spectral analysis. A comparative analysis of 1% extracts of fresh and dry H. perforatum was performed in order to determine the local extremums for effects of nerve tissue conductivity at (-0.1112) eV, anti-inflammatory (-0.1212) eV, anti-tumor effects (-0.1387) eV. The results showed stimulating effect on the nervous system and improvement of nerve conduction (local extremums E=-0.1112 eV)(?=11.15 ?m) (?=897 cm-1), as well as anti-inflammatory effect (E = -0.1212 eV)( ?=10.23 ?m) (?=978 cm-1) and inhibition of development of tumor cells at a molecular level (E=-0.1387 eV) (?=8.95 ?m) (?=1117 cm-1). It was found that clusters of 16 and 15 water molecules are formed in the water herbal extracts of fresh H. perforatum and of dry H. perforatum with AgNPs 30 ppm. The fresh plant showed better results then the dry one. The addition of colloidal nano silver 30 ppm led to better results of the drug.

Graphene-Based Materials Prove to Be a Promising Candidate for Nerve Regeneration Following Peripheral Nerve Injury

Peripheral nerve injury is a common medical condition that has a great impact on patient quality of life. Currently, surgical management is considered to be a gold standard first-line treatment; however, is often not successful and requires further surgical procedures. Commercially available FDA- and CE- approved decellularized nerve conduits offer considerable benefits to patients suffering from a completely transected nerve but they fail to support neural regeneration in gaps >30 mm. To address this unmet clinical need, current research is focused on biomaterial-based therapies to regenerate dysfunctional neural tissues, specifically damaged peripheral nerve, and spinal cord. Recently, attention has been paid to the capability of graphene-based materials (GBMs) to develop bifunctional scaffolds for promoting nerve regeneration, often via supporting enhanced neural differentiation. The unique features of GBMs have been applied to fabricate an electroactive conductive surface in order to direct stem cells and improve neural proliferation and differentiation. The use of GBMs for nerve tissue engineering (NTE) is considered an emerging technology bringing hope to peripheral nerve injury repair, with some products already in preclinical stages. This review assesses the last six years of research in the field of GBMs application in NTE, focusing on the fabrication and effects of GBMs for neurogenesis in various scaffold forms, including electrospun fibres, films, hydrogels, foams, 3D printing, and bioprinting.

Cryoneurolysis for Digital Neuralgia in Professional Baseball Players: A Case Series

ObjectiveWe describe a non-surgical approach to refractory digital neuralgia using cryoneurolysis in a series of 3 professional baseball players.BackgroundThumb injuries are common in baseball players and can sometimes be challenging to effectively manage. Depending on the injury, current treatments include anti-inflammatories, immobilization, physical therapy, corticosteroid injections, and/or surgery. A subset of patients, however, fail nonoperative management yet do not have a clear indication for surgery. Cryoneurolysis or cyroanalgesia is an FDA-approved form of neuromodulation, which has been used safely and effectively on a variety of peripheral nerves. The mechanism of action involves percutaneous introduction of a small probe under local anesthetic to nerve tissue using ultrasound guidance. The probe is then cooled to −88°C using nitrous oxide, which results in secondary Wallerian degeneration. Axonal and myelin regeneration occurs completely in 3–6 months.Design/MethodsVisualization of the superficial radial sensory and ulnar digital nerve were obtained under ultrasound. The skin was prepared in sterile fashion. A 22-gauge 1-½ inch needle was then advanced with ultrasound guidance, and local anesthetic was applied. Both treatment sites were marked with skin marker. Cryoneurolysis was employed using a 5 mm tip. 60-second treatment cycles were performed at each site. Each of the cycles resulted in a 5 × 7 mm lesion visible as hypoechoic signal.ResultsAll 3 players endorsed significant and prolonged relief and were able to return to an elite level of play.ConclusionsThis manuscript is subject to all of the limitations of a case series, and larger rigorous studies are needed to illuminate causal inferences. Novel, complex technologies may also be more susceptible to placebo effect. Nonetheless, we are able to report marked efficacy and safety from cryoneurolysis of the ulnar digital nerve and the superficial radial sensory nerve in a small group of elite baseball players with refractory digital neuralgia.

The Repression of the HMGB1-TLR4-NF-κB Signaling Pathway by Safflower Yellow May Improve Spinal Cord Injury

Spinal cord injury (SCI) often results in abnormal sensory and motor functions. Current interventions for SCI in the clinical setting are not effective partly due to the complexity concerning its pathophysiological mechanism. In the wake of SCI, considerable inflammatory cells assemble around the injured area that induces a series of inflammatory reactions and aggravates tissue lesions, thereby affecting the recovery of the damaged nerve tissue. Therefore, the inhibition of inflammatory responses can improve the repair of the injured spinal cord tissue. Safflower Yellow (SY) is the main active ingredient of Carthamus tinctorius. SY has anti-inflammatory effect, as it can inhibit IκBα phosphorylation to impede the NF-κB signaling pathway and p53 nuclear translocation. Besides, SY can limit the release of pro-inflammatory factors, which in turn may alleviate secondary SCI and prevent further complications. In this report, we analyze the pathophysiological mechanism of SCI, the role of inflammatory responses, and how SY interferes with the HMGB1-TLR-4-NF-κB signaling pathway to attenuate inflammatory responses in SCI.