Peripheral nerve injuries are serious conditions, and surgical treatment has critical limitations. Therefore, nerve guidance conduits (NGCs) are proposed as an alternative. In this study, multifunctional NGCs are fabricated for the regeneration of injured peripheral nerves. Graphene oxide (GO) and gelatin-methacrylate (GelMA) are polymerized and chemically reduced to form reduced (GO/GelMA) (r(GO/GelMA)). The prepared materials present good electrical conductivity, flexibility, mechanical stability, and permeability, which are suitable for use as NGCs. In vitro studies show 2.1-and 1.4-fold promotion of neuritogenesis of PC12 neuronal cells on r(GO/GelMA) compared to GelMA and unreduced GO/GelMA, respectively. Animal studies using a rat sciatic nerve injury model with a 10 mm gap between the proximal and distal regions of the defect reveal that r(GO/GelMA) NGCs significantly enhance peripheral nerve regeneration, indicated by improved muscle weight increase, electro-conduction velocity, and sciatic nerve function index. Specifically, r(GO/GelMA) NGCs are utilized to potentiate regrowth with myelination in rat sciatic nerves followed by histological, immunohistological, and morphometrical analyses. This study successfully shows the feasibility of electrically conductive hydrogel NGCs as functional conduits for improved nerve regeneration in a preclinical study, where these NGCs can not only mimic nerve tissues but also strongly promote nerve regeneration.

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If only allowed to proceed naturally, the bone-healing process can take several weeks, months, or even years depending on the injury size. In terms of bone-healing speed, many studies have been conducted investigating the deliverance of various growth factors of implantable biomaterials to shorten the time for bone regeneration. However, there may be side effects such as nerve pain, infection, or ectopic bone formation. As an alternative method, we focused on biophysical guidance, which provided similar topographical cues to the cellular environment to recruit host cells for bone defect healing. In this study, we hypothesized that aligned nanotopographical features have enhanced osteoblast recruitment, migration, and differentiation without external stimuli. We designed and fabricated a biodegradable poly­(lactic-co-glycolic acid) nanopatterned patch using simple solvent casting and capillary force lithography. We confirmed that a biodegradable nanopatterned patch (BNP) accelerated the migration of osteoblasts according to the orientation of the patterned direction. These highly aligned osteoblasts may contribute to in vitro osteogenic differentiation, such as alkaline phosphate activity, mineralization, and calcium deposition, compared to the biodegradable flat patch (BFP). To demonstrate bone defect healing by BNP guidance in vivo, we implanted either whole or bridge BNP on the critical size defect of mouse calvarial (ø 4 mm) or tibia bone (3 × 7 mm2). Only the BNP-treated group showed faster new bone formation and compact bone regeneration at the calvarial or tibia bone defect area compared to BFP at 4 or 8 weeks. Bridge BNP guided, in particular, the regeneration of new bone formation along the parallel direction of nanopatterned substrates. Here, we show that a BNP with biophysical guidance should be suitable for use in bone tissue regeneration through accelerated migration of the intact host cell.

BackgroundThe extracellular matrix (ECM) can directly or indirectly influence on regulation of cell functions such as cell adhesion, migration, proliferation and differentiation. The cell derived ECM (CD-ECM) is a useful in vitro model for studying the comprehensive functions of CD-ECM because it maintains a native-like structure and composition. In this study, the CD-ECM is obtained and a test is carried out to determine the effectiveness of several combinations of decellularized methods. These methods were used to regulate the optimal ECM compositions to be induced by osteogenic differentiation using primary isolated osteoblasts.ResultWe investigated the effect of osteoblasts re-seeded onto normal osteoblast ECM under the growth medium (GM-ECM) and the osteogenic differentiation medium (OD-ECM). The osteoblasts were then cultured statically for 1, 2, and 4 weeks in a growth medium or differentiation medium. Before osteoblast culture, we performed immunostaining with filamentous actin and nuclei, and then performed DNA quantification. After each culture period, the osteogenic differentiation of the osteoblasts re-seeded on the OD-ECMs was enhanced osteogenic differentiation which confirmed by alkaline phosphatase staining and quantification, Alizarin Red S staining and quantification, and von Kossa staining. The OD-ECM-4 W group showed more effective osteogenic differentiation than GM-ECM and OD-ECM-2 W.ConclusionsThe OD-ECM-4 W has a better capacity in a microenvironment that supports osteogenic differentiation on the GM-ECM and OD-ECM-2 W. The ECM substrate has a wide range of applications as cell culture system or direct differentiation of stem cell and excellent potential as cell-based tissue repair in orthopedic tissue engineering.

Inspired by the rolling mechanism of the proboscis of a butterfly, rollable electronics that can be rolled and unrolled to a great extent on demand are developed. Generally, electronic devices that are attached to various surfaces to acquire biosignals require mechanical flexibility and sufficient adhesive force. The rollable platform provides sufficient force that grips onto the entire target surface without destroying the target organ. To prove the versatility of our device not only in gripping and detecting biosignals from micro objects but also in performing a variety of functions, thin-film electronics including a heater, strain sensor and temperature sensor are constructed on the rollable platform, and it is confirmed that all the electronics operate normally in the rolled and unrolled states without breakdown. Then, micro bio-objects are gripped by using the rollable platform, and their tiny motions are successfully detected with the sensor on the platform. Furthermore, the detection of the pulse wave signals of swine under diverse experimental conditions is successfully conducted by rolling up the rollable system around the blood vessel of the swine, the result of which proves the feasibility of a rollable platform as a biomedical device.

Mesenchymal stem cell (MSC) based therapy holds great potential for treating numerous diseases owing to their capability to heal injured tissue/organs through paracrine factors secretion and immunomodulation. Despite the high hopes, the low viability of transplanted cells in the injured tissues due to the elevated oxidative stress levels remains the largest obstacle in MSCbased cell therapy. To achieve desired therapeutic efficiency, the survival of the transplanted MSCs in the high oxidative stress environment needs to be ensured. Herein, we proposed the use of a ROS-scavenging nanozyme to protect transplanted MSCs from oxidative stress-mediated apoptosis and thereby improve the therapeutic effect. Prussian blue (PB) nanoparticles as a biocompatible ROS-scavenging nanozyme were incorporated into the MSCs without affecting the stemness and differentiation potential of MSCs. The nanozyme impregnation significantly improved the survival of MSCs in a high oxidative stress condition as well as augmented their paracrine effect and anti-inflammatory properties, resulting in a profound therapeutic effect in vivo in the liver ischemia-reperfusion (I/R) injury animal model. Our results indicated that the nanozyme incorporation into MSCs is a simple but efficient way to improve the therapeutic potential of MSC-based cell therapy.