Mesenchymal Stem Cells and Exosomes: A Novel Therapeutic Approach for Corneal Diseases.

The cornea, with its delicate structure, is vulnerable to damage from physical, chemical, and genetic factors. Corneal transplantation, including penetrating and lamellar keratoplasties, can restore the functions of the cornea in cases of severe damage. However, the process of corneal transplantation presents considerable obstacles, including a shortage of available donors, the risk of severe graft rejection, and potentially life-threatening complications. Over the past few decades, mesenchymal stem cell (MSC) therapy has become a novel alternative approach to corneal regeneration. Numerous studies have demonstrated the potential of MSCs to differentiate into different corneal cell types, such as keratocytes, epithelial cells, and endothelial cells. MSCs are considered a suitable candidate for corneal regeneration because of their promising therapeutic perspective and beneficial properties. MSCs compromise unique immunomodulation, anti-angiogenesis, and anti-inflammatory properties and secrete various growth factors, thus promoting corneal reconstruction. These effects in corneal engineering are mediated by MSCs differentiating into different lineages and paracrine action via exosomes. Early studies have proven the roles of MSC-derived exosomes in corneal regeneration by reducing inflammation, inhibiting neovascularization, and angiogenesis, and by promoting cell proliferation. This review highlights the contribution of MSCs and MSC-derived exosomes, their current usage status to overcome corneal disease, and their potential to restore different corneal layers as novel therapeutic agents. It also discusses feasible future possibilities, applications, challenges, and opportunities for future research in this field.

Current Advances in Regenerative Strategies for Dry Eye Diseases: A Comprehensive Review.

Dry eye disease (DED) is an emerging health issue affecting millions of individuals annually. Ocular surface disorders, such as DED, are characterized by inflammation triggered by various factors. This condition can lead to tear deficiencies, resulting in the desiccation of the ocular surface, corneal ulceration/perforation, increased susceptibility to infections, and a higher risk of severe visual impairment and blindness. Currently, the clinical management of DED primarily relies on supportive and palliative measures, including the frequent and lifelong use of different lubricating agents. While some advancements like punctal plugs, non-steroidal anti-inflammatory drugs, and salivary gland autografts have been attempted, they have shown limited effectiveness. Recently, there have been promising developments in the treatment of DED, including biomaterials such as nano-systems, hydrogels, and contact lenses for drug delivery, cell-based therapies, biological approaches, and tissue-based regenerative therapy. This article specifically explores the different strategies reported so far for treating DED. The aim is to discuss their potential as long-term cures for DED while also considering the factors that limit their feasibility and effectiveness. These advancements offer hope for more effective and sustainable treatment options in the future.

3D bioprinted complex constructs reinforced by hybrid multilayers of electrospun nanofiber sheets.

Despite the usefulness of hydrogels for cell-based bioprinting, the fragility of their resulting constructs has hindered their practical applications in tissue engineering research. Here, we suggest a hybrid integration method based on cell-hydrogel bioprinting that includes alternate layering of flexible nanofiber (NF) sheets. Because the bioprinting was implemented on a nanofibrous surface, the hydrogel-based materials could be printed with enhanced shape resolution compared to printing on a bare hydrogel. Furthermore, the insertion of NF sheets was effective for alleviating the shrinkage distortion of the hydrogel construct, which is inherently generated during the crosslinking process, thereby enhancing shape fidelity throughout the three-dimensional (3D) architecture. In addition to the structural precision, the NF-embedded constructs improved the mechanical properties in terms of compressive strength, modulus, and resilience limit (up to four-fold enhancement). With structural and mechanical supports, we could 3D fabricate complex constructs, including fully opened internal channels, which provided a favorable perfusion condition for cell growth. We confirmed the enhanced bioactivity of the NF-embedded bioprinted construct via cell culture experiments with 80% enhanced proliferation compared to the monolithic one. The synergistic combination of the two flexible materials, NFs and hydrogels, is expected to have extensive applicability in soft tissue engineering.

Effect and neurophysiological mechanism of acupuncture in patients with chronic sciatica: protocol for a randomized, patient-assessor blind, sham-controlled clinical trial.

BACKGROUND: Sciatica is a relatively frequent illness that easily becomes a chronic and relapsing condition. Although numerous systematic reviews have analyzed various therapies for sciatica, the validity of their included studies is limited. Considering the limitations of conventional treatment options for sciatica, acupuncture is a possible option; however, evidence supporting its efficacy and mechanism in patients with sciatica is lacking. The aim of this proposed protocol is to investigate the effect and neurophysiological mechanism of acupuncture in patients with chronic sciatica. METHODS/DESIGN: This study is a randomized, patient-assessor blind, two-arm, parallel, non-penetrating, sham-controlled clinical trial. Eligible participants will include adults (aged 19-70 years old) with a clinical diagnosis of chronic sciatica (40 mm or more of a 100-mm visual analog scale (VAS) for bothersomeness) blinded to the treatment received. Patients will be randomly allocated into the acupuncture treatment group (manual acupuncture plus electroacupuncture (EA), n = 34) or the sham acupuncture control group (sham acupuncture plus placebo EA without electrical stimulation, n = 34). Groups will receive treatment twice a week for a total of eight sessions over 4 weeks. Functional magnetic resonance imaging will be implemented at baseline and endpoint to investigate the mechanism of acupuncture. The primary outcome measure is the VAS for bothersomeness and secondary outcomes include the VAS for pain intensity, Oswestry Disability Index, EuroQol 5-Dimension, Coping Strategy Questionnaire, Beck's Depression Inventory, and State-Trait Anxiety Inventory. Adverse events will be assessed at every visit. DISCUSSION: The results of this trial (which will be available in 2020) should provide important clinical evidence for the effect of acupuncture and demonstrate how acupuncture can be helpful for the treatment of chronic sciatica. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03350789 . Registered on 15 November 2017.

Fabrication of 3D freeform porous tubular constructs with mechanical flexibility mimicking that of soft vascular tissue.

Three-dimensional (3D) printing, with its capability for producing arbitrary shapes, has been extensively studied for tissue engineering applications. However, clinical applications, especially for soft tissues, have been limited due to mechanical mismatch between the 3D-printed artificial tissues and the native tissues. Here, we suggest an integrative method of 3D printing, dip coating, and salt leaching for the fabrication of soft 3D freeform porous tubes, which are expected to be applied to the engineering of vascular tissues. Owing to their porous morphology and controlled wall thickness, the processed tubular constructs had flexible properties comparable to those of native soft tissues with a modulus range of several MPa. When thermoplastic polyurethane (TPU) was used as the dip-coating material, the porous tube exhibited a low tensile modulus from 1.47 to 2.47 MPa and a high elongation limit of over 400%. These flexible properties, which were clearly differentiated from the stiffness of 3D-printed samples with moduli of tens or hundreds of MPa, were confirmed to mimic the mechanical properties of native tissues. Furthermore, by varying the material composition in the dip-coating process, the flexibility of the tube could be modulated when stiffer polycaprolactone (PCL) layers were combined. In addition, such a combination using biocompatible materials could be expected to provide safer interaction at surgical interfaces. Synergistically with the mechanical flexibility, since the proposed method was based on a 3D-printed template, the resulting construct would have extensive applicability in patient-specific tissue engineering.