Coaxial 3D printing of hierarchical structured hydrogel scaffolds for on-demand repair of spinal cord injury.

After spinal cord injury (SCI), endogenous neural stem cells (NSCs) near the damaged site are activated, but few NSCs migrate to the injury epicenter and differentiate into neurons because of the harsh microenvironment. It has demonstrated that implantation of hydrogel scaffold loaded with multiple cues can enhance the function of endogenous NSCs. However, programming different cues on request remains a great challenge. Herein, a time-programmed linear hierarchical structure scaffold is developed for spinal cord injury recovery. The scaffold is obtained through coaxial 3D printing by encapsulating a dual-network hydrogel (composed of hyaluronic acid derivatives and N-cadherin modified sodium alginate, inner layer) into a temperature responsive gelatin/cellulose nanofiber hydrogel (Gel/CNF, outer layer). The reactive species scavenger, metalloporphyrin, loaded in the outer layer is released rapidly by the degradation of Gel/CNF, inhibiting the initial oxidative stress at lesion site to protect endogenous NSCs; while the inner hydrogel with appropriate mechanical support, linear topology structure and bioactive cues facilitates the migration and neuronal differentiation of NSCs at the later stage of SCI treatment, thereby promoting motor functional restorations in SCI rats. This study offers an innovative strategy for fabrication of multifunctional nerve regeneration scaffold, which has potential for clinical treatment of SCI. STATEMENT OF SIGNIFICANCE: Two major challenges facing the recovery from spinal cord injury (SCI) are the low viability of endogenous neural stem cells (NSCs) within the damaged microenvironment, as well as the difficulty of neuronal regeneration at the injured site. To address these issues, a spinal cord-like coaxial scaffold was fabricated with free radical scavenging agent metalloporphyrin Mn (III) tetrakis (4-benzoic acid) porphyrin and chemokine N-cadherin. The scaffold was constructed by 3D bioprinting for time-programmed protection and modulation of NSCs to effectively repair SCI. This 3D coaxially bioprinted biomimetic construct enables multi-factor on-demand repair and may be a promising therapeutic strategy for SCI.

Intradural disc herniation at the L2/3 level: a case report and literature review.

BACKGROUND: Intradural lumbar disc herniation (ILDH) is special type of lumbar disc herniation in which the lumbar nucleus pulposus prolapses and enters the dura mater. ILDHs comprise 0.04-0.33% of all herniated discs. In most cases, the diagnosis could not be confirmed preoperatively by identifying the typical features of ILDH in radiological evaluation. In the current report, we present a case of ILDH at lumbar 2/3 level and discuss the clinical presentations, typical imaging features, treatments, and outcomes. CASE DESCRIPTION: We describe a rare case of ILDH. The patient was a 65-year-old man with pain in waist and back, and with bilateral radiating pain of lower extremities and fatigue for more than 2 weeks. Magnetic resonance imaging (MRI) revealed a large round, low-density mass at lumbar 2/3, which was easily mimicked as an intradural spinal tumor lesion. While enhanced MRI showed the typical rim enhancement sign and "Hawk beak" sign. Due to progressive decrease in muscle strength in both lower limbs, posterior microscopically assisted laminectomy, dural incision of the lumbar 2/3 was performed. Pathological examination revealed degenerated fibrous connective tissue and cartilage tissue. The patient's lower back pain and radiating pain and numbness of both legs improved remarkably postoperatively, and he became asymptomatic at 3 months and 1-year postoperatively. CONCLUSIONS: ILDH is a rare intervertebral disc herniation in clinical practice. The pathogenesis of ILDH may be related to aseptic inflammatory edema, closely fixing of ventral dura and the posterior longitudinal ligament, repeated mechanical action and chemical corrosion. Typical rim enhancement sign, "Hawk beak" sign and "Y" sign are important features of MRI in diagnosing ILDH, and intraspinal gas is also helpful in computed tomography (CT) diagnosis of ILDH. Prompt microscopically assisted laminectomy, dura mater incision to remove the intradural disc, pedicle screw fixation regardless of fusion, surgical results are usually favorable. We also reviewed the literature and discussed the epidemiology, potential pathogenesis, diagnosis, treatment and poor prognostic factors of ILDH.

Biomechanical evaluation of axial-loading simulated experiment in wrist fractures: a finite element analysis.

OBJECTIVE: To assess the biomechanical properties that influence wrist fracture, so as to provide the theoretical basis for simulation experiments to aid the optimal design of wrist protectors. METHODS: Six cadaveric wrists were included as experimental specimens. Wrist specimens wearing wrist protectors formed the experimental group and unprotected wrist specimens formed the control group. The wrist specimens were axially loaded under physiological loads and the stress magnitude and distribution of the experimental and control groups were obtained. A three-dimensional wrist finite element model of a healthy volunteer was developed to verify the rationality and effectiveness of the cadaveric wrist models. RESULTS: Under normal physiological loads, the stress on the radioulnar palmar unit was high and manifested in the form of pressure, while the stress on the radioulnar dorsal unit was lower and manifested in the form of tension. The stresses on the radial distal palmar, ulnar distal palmar, radial distal dorsal, ulnar distal dorsal, radial proximal palmar and ulnar proximal palmar units in the experimental group were less than those in the control group. CONCLUSION: Under physiological loads, wearing a wrist protector can reduce the stress on the radioulnar distal palmar, radioulnar proximal palmar and radioulnar distal dorsal units, while having no obvious effect on the radioulnar proximal dorsal units.

The anti-tumor effect of pachymic acid on osteosarcoma cells by inducing PTEN and Caspase 3/7-dependent apoptosis.

Pachymic acid (PA) is a lanostane type triterpenoid isolated from Poria cocos, which possesses an anti-tumor effect in breast cancer, prostate cancer, lung cancer, and bladder cancer cells. In this study, we investigated the effect of PA on the growth and apoptosis of human immortalized cell line (HOS) and primary osteosarcoma cells by a Cell Counting Kit-8 (CCK-8) and Annexin V and propidium iodide (PI) staining, respectively. Western blot was used to measure the expression of cleaved Caspase 3, PTEN, and AKT, as well as the AKT phosphorylation. The Caspase 3 activity was determined using the Caspase-3 Colorimetric Assay Kit. From the results, PA significantly reduced cell proliferation in a concentration- and time-dependent manner. PA also induced cell apoptosis in a dose-dependent fashion. PA treatment led to increased Caspase 3 activation and PTEN expression, as well as reduced AKT phosphorylation. Moreover, Ac-DEVD-CHO (a Caspase 3/7 inhibitor) pre-treatment or PTEN knockdown partially blocked the effects of PA on cell proliferation and apoptosis. Caspase 3/7 inhibitor had an additive effect with PTEN knockdown. Collectively, our results suggested that induction of apoptosis by PA was mediated in part by PTEN/AKT signaling and Caspase 3/7 activity. This study provides evidence that PA might be useful in the treatment of human osteosarcoma.

Ellipticine inhibits the proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via the STAT3 pathway.

OBJECTIVE: Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an alkaloid isolated from Apocyanaceae plants. This study was designed to investigate the effects of ellipticine on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). METHODS: RA-FLSs were exposed to different concentrations of ellipticine (i.e., 0.5, 1, 2, 4 and 8 µM) for 24-72h and measured for viability, proliferation and apoptosis. The involvement of signal transducer and activators of transcription 3 (STAT3) signaling in the action of ellipticine was determined by Western blot analysis, luciferase reporter assay and rescue experiments. RESULTS: Ellipticine treatment significantly inhibited the viability and proliferation of RA-FLSs in a concentration-dependent manner. In contrast, ellipticine exposure did not alter the viability of normal human FLSs. Moreover, ellipticine triggered significant apoptosis and increased caspase-3 activity in RA-FLSs. Mechanistically, ellipticine reduced the phosphorylation of STAT3 and downregulated the expression of Mcl-1, cyclin D1 and Bcl-2. Luciferase reporter assay demonstrated that ellipticine treatment led to a significant inhibition of STAT3-mediated transcriptional activity in RA-FLSs. Overexpression of constitutively active STAT3 reversed the suppressive effects of ellipticine on RA-FLSs, which was accompanied by restoration of Mcl-1, cyclin D1 and Bcl-2. DISCUSSION AND CONCLUSIONS: Ellipticine shows anti-proliferative and pro-apoptotic effects on RA-FLSs through inhibition of the STAT3 pathway and may have therapeutic potential in RA.