Advanced Nanomaterials in Medical 3D Printing.

3D printing is now recognized as a significant tool for medical research and clinical practice, leading to the emergence of medical 3D printing technology. It is essential to improve the properties of 3D-printed products to meet the demand for medical use. The core of generating qualified 3D printing products is to develop advanced materials and processes. Taking advantage of nanomaterials with tunable and distinct physical, chemical, and biological properties, integrating nanotechnology into 3D printing creates new opportunities for advancing medical 3D printing field. Recently, some attempts are made to improve medical 3D printing through nanotechnology, providing new insights into developing advanced medical 3D printing technology. With high-resolution 3D printing technology, nano-structures can be directly fabricated for medical applications. Incorporating nanomaterials into the 3D printing material system can improve the properties of the 3D-printed medical products. At the same time, nanomaterials can be used to expand novel medical 3D printing technologies. This review introduced the strategies and progresses of improving medical 3D printing through nanotechnology and discussed challenges in clinical translation.

3D printed elastic hydrogel conduits with 7,8-dihydroxyflavone release for peripheral nerve repair.

Nerve guide conduit is a promising treatment for long gap peripheral nerve injuries, yet its efficacy is limited. Drug-releasable scaffolds may provide reliable platforms to build a regenerative microenvironment for nerve recovery. In this study, an elastic hydrogel conduit encapsulating with prodrug nanoassemblies is fabricated by a continuous 3D printing technique for promoting nerve regeneration. The bioactive hydrogel is comprised of gelatin methacryloyl (GelMA) and silk fibroin glycidyl methacrylate (SF-MA), exhibiting positive effects on adhesion, proliferation, and migration of Schwann cells. Meanwhile, 7,8-dihydroxyflavone (7,8-DHF) prodrug nanoassemblies with high drug-loading capacities are developed through self-assembly of the lipophilic prodrug and loaded into the GelMA/SF-MA hydrogel. The drug loading conduit could sustainedly release 7,8-DHF to facilitate neurite elongation. A 12 â€‹mm nerve defect model is established for therapeutic efficiency evaluation by implanting the conduit through surgical suturing with rat sciatic nerve. The electrophysiological, morphological, and histological assessments indicate that this conduit can promote axon regeneration, remyelination, and function recovery by providing a favorable microenvironment. These findings implicate that the GelMA/SF-MA conduit with 7,8-DHF release has potentials in the treatment of long-gap peripheral nerve injury.

Nerve transfer with 3D-printed branch nerve conduits.

Background: Nerve transfer is an important clinical surgical procedure for nerve repair by the coaptation of a healthy donor nerve to an injured nerve. Usually, nerve transfer is performed in an end-to-end manner, which will lead to functional loss of the donor nerve. In this study, we aimed to evaluate the efficacy of 3D-printed branch nerve conduits in nerve transfer. Methods: Customized branch conduits were constructed using gelatine-methacryloyl by 3D printing. The nerve conduits were characterized both in vitro and in vivo. The efficacy of 3D-printed branch nerve conduits in nerve transfer was evaluated in rats through electrophysiology testing and histological evaluation. Results: The results obtained showed that a single nerve stump could form a complex nerve network in the 3D-printed multibranch conduit. A two-branch conduit was 3D printed for transferring the tibial nerve to the peroneal nerve in rats. In this process, the two branches were connected to the distal tibial nerve and peroneal nerve. It was found that the two nerves were successfully repaired with functional recovery. Conclusions: It is implied that the two-branch conduit could not only repair the peroneal nerve but also preserve partial function of the donor tibial nerve. This work demonstrated that 3D-printed branch nerve conduits provide a potential method for nerve transfer.

Development and Evaluation of MOVit: An Exercise-Enabling Interface for Driving a Powered Wheelchair.

Powered wheelchair users can experience negative health effects from reduced physical activity. If a user could exercise by driving the chair, it might improve fitness. This paper presents the development of MOVit, an exercise-enabling, wheelchair driving interface. The design goal of MOVit was that users cyclically move their arms to drive the chair, thereby providing a light level of exercise while driving. MOVit supports this arm movement with custom mobile arm supports that also serve as the sensors that provide controller inputs. Here, we first quantified how increasing the frequency and amplitude of arm movement increase oxygen consumption and heart rate. Then, we evaluated two novel control methods for driving by moving the arm supports. Participants without impairment ( N = 24 ) were randomized to one of the two methods, or conventional joystick control, and performed driving tests over two days on a simulator and test course. Our results indicate that driving speed and accuracy were significantly lowered with the exercise-enabling methods compared to joystick control (ANOVA, ), but the decreases were small (speed was ~0.1 m/s less and course tracking error ~1 cm greater). These results show, for the first time, the feasibility of exercising while driving a powered wheelchair.

MMP-2 and MMP-9 contribute to the angiogenic effect produced by hypoxia/15-HETE in pulmonary endothelial cells.

Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are the predominant gelatinases in the developing lung. Studies have shown that the expression of MMP-2 and MMP-9 is upregulated in hypoxic fibroblasts, 15-hydroxyeicosatetraenoic acid (15-HETE) regulated fibroblasts migration via modulating MMP-2 or MMP-9, and that hypoxia/15-HETE is a predominant contributor to the development of pulmonary arterial hypertension (PAH) through increased angiogenesis. However, the roles of MMP-2 and MMP-9 in pulmonary arterial endothelial cells (PAECs) angiogenesis as well as the molecular mechanism of hypoxia-regulated MMP-2 and MMP-9 expression have not been identified. The aim of this study was to investigate the role of MMP-2 and MMP-9 in PAEC proliferation and vascular angiogenesis and to determine the effects of hypoxia-induced 15-HETE on the expression of MMP-2 and MMP-9. Western blot, immunofluorescence, and real-time PCR were used to measure the expression of MMP-2 and MMP-9 in hypoxic PAECs. Immunohistochemical staining, flow cytometry, and tube formation as well as cell proliferation, viability, scratch-wound, and Boyden chamber migration assays were used to identify the roles and relationships between MMP-2, MMP-9, and 15-HETE in hypoxic PAECs. We found that hypoxia increased MMP-2 and MMP-9 expression in pulmonary artery endothelium both in vivo and in vitro in a time-dependent pattern. Moreover, administration of the MMP-2 and MMP-9 inhibitor MMI-166 significantly reversed hypoxia-induced increases in right ventricular systemic pressure (RVSP), right ventricular function, and thickening of the tunica media. Furthermore, up-regulation of MMP-2 and MMP-9 expression was induced by 15-HETE, which regulates PAEC proliferation, migration, and cell cycle transition that eventually leads to angiogenesis. Our study demonstrated that hypoxia increases the expression of MMP-2 and MMP-9 through the 15-lipoxygenase/15-HETE pathway, and that MMP-2 and MMP-9 promote PAEC angiogenesis. These findings suggest that MMP-2 and MMP-9 may serve as new potential therapeutic targets for the treatment of PAH.