ObjectiveTo review the application and research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering.
MethodsThe original articles about in vivo bioreactor that can enhance vascularization of tissue engineered bone were extensively reviewed and analyzed.
ResultsThe in vivo bioreactor can be created by periosteum, muscle, muscularis membrane, and fascia flap as well as biomaterials. Using in vivo bioreactor can effectively promote the establishment of a microcirculation in the tissue engineered bones, especially for large bone defects. However, main correlative researches, currently, are focused on animal experiments, more clinical trials will be carried out in the future.
ConclusionWith the rapid development of related technologies of bone tissue engineering, the use of in vivo bioreactor will to a large extent solve the bottleneck limitations and has the potential values for clinical application.
ObjectiveTo investigate the changes in the nerve fiber layer of the cornea in patients with demyelinating optic neuritis (DON) and its correlation with visual acuity. MethodsA cross-sectional study. From March 2021 to July 2022, 27 cases (39 eyes) of DON patients diagnosed in the Department of Neurology and Ophthalmology of Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. According to the serological test results, the patients were divided into aquaporin 4 antibody associated optic neuritis (AQP4-ON group) and myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON group), with 15 cases (19 eyes) and 12 cases (20 eyes) respectively. According to previous history of glucocorticoid treatment, the patients were divided into glucocorticoid treated group and non-glucocorticoid treated group, with 17 cases (27 eyes) and 10 cases (12 eyes) respectively. Twenty healthy volunteers (20 eyes) with age- and gender-matched were selected as the control group. All eyes underwent best corrected visual acuity (BCVA) and in vivo confocal microscopy (IVCM) examinations. BCVA was performed using Snellen's standard logarithmic visual acuity chart, which was converted into logarithmic minimum angle resolution (logMAR) visual acuity during statistics. The corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve fiber branch length (CNBL), corneal nerve fiber branch density (CNBD) and the density of corneal dendritic cells (DC) were detected by IVCM examination. Parameter comparison between groups by t-test and Kruskal-Wallis rank sum test. The correlation between logMAR BCVA and pamameters of corneal nerve fibers were analyzed using Spearman analysis. ResultsThe CNFL, CNFD, and CNBL of the DON group and the control group were (10.67±2.55) mm/mm2, (57.78±12.35) root/mm2, (3.27±1.34) mm/mm2, and (13.74±3.05) mm/mm2, (70.95±13.14) root/mm2, and (4.22±1.03) mm/mm2, respectively; the difference in CNFL, CNFD, and CNBL between the two groups were statistically significant (t=4.089, 3.795, 2.773; P＜0.05). The CNFL, CNBL, and CNBD of the affected eyes in the MOG-ON group and AQP4-ON group were (12.02±2.13) mm/mm2, (3.80±1.19) mm/mm2, (47.97±8.86) fibers/mm2, and (9.25±2.19) mm/mm2, (2.72±1.19) mm/mm2, (39.43±13.86) fibers/mm2, respectively; the differences in CNFL, CNBL, and CNBD between the two groups were statistically significant (t=－4.002, －2.706, －2.306; P＜0.05). The corneal DC density of the patients in the hormone treated group and the non-hormone treated group was (24.43±8.32) and (41.22±9.86) cells/mm2, respectively. The difference in corneal DC density between the two subgroups was statistically significant (P＜0.001). Correlation analysis showed that there was a significant negative correlation between logMAR BCVA and CNBL and CNFL in patients with DON (r=－0.422, －0.456; P＜0.05). ConclusionsThere are different degrees of corneal nerve fiber damage in patients with different types of DON. There was a negative correlation between BCVA and the length of corneal nerve fibers.
ObjectiveTo observe the in vivo three-dimensional (3-D) transient motion characteristics of the subaxial cervical spine in healthy adults.
MethodsSeventeen healthy volunteers without cervical spine related diseases were recruited for this study, including 8 males and 9 females with a mean age of 26 years (range, 23-41 years). The vertebral segment motion of each subject was reconstructed with CT, and Rhinoceros 4.0 solid modeling software were used for 3-D reconstruction model of the subaxial cervical spine. In vivo cervical vertebral motion in flexionextension, left and right bending, left and right rotation was observed with dual fluoroscopic imaging system (DFIS). Coordinate systems were established at the vertebral center of C3-7 to obtain the intervertebral range of motion (ROM) and displacement at C3, 4, C4, 5, C5, 6, and C6, 7. The X-axis pointed to the left along the coronal plane, the Y-axis pointed to the back along the sagittal plane, and the Z-axis perpendicular to the X-Y plane pointed to the head. The ROM along X, Y, and Z axises were represented by rotation in flexion-extension (α), in left-right bending (β), and in left-right twisting (γ) respectively, and the displacement in left-right direction (x), in anterior-posterior direction (y), and in proximaldistal direction (z), respectively.
ResultsIn flexion and extension, the displacement in anterior-posterior direction of C6, 7 was significantly less that of other segments (P<0.05), but the displacements in left-right direction and in proximaldistal direction showed no significant difference between segments (P>0.05); the ROM values in flexion-extension of C4, 5 and C5, 6 were significantly larger than those of C3, 4 and C6, 7 (P<0.05), and the ROM value in left-right twisting of C4, 5 was significantly larger than those of C5, 6 and C6, 7 (P<0.05), but the ROM value in left-right bending showed no significant difference between segments (P>0.05). In left and right bending, there was no significant difference in the displacement between other segments (P>0.05) except that the displacement in anterior-posterior direction of C3, 4 was significantly larger than that of C4, 5 (P<0.05), and that the displacement in proximal-distal direction of C6, 7 was significantly less than that of C3, 4 and C4, 5 (P<0.05); no significant difference was shown in the ROM value between segments (P>0.05), except that the ROM value in left-right twisting of C3, 4 was significantly larger than that of C5, 6 and C6, 7 (P<0.05). In left and right rotation, the ROM value in left-right twisting of C3, 4 was significantly larger than that of C4, 5 and C6, 7 (P<0.05), and the displacement and ROM value showed no significant differece between other segments (P>0.05).
ConclusionThe intervertebral motions of the cervical spine show different characters at different levels. And the 6-degree-of-freedom data of the cervical vertebrae are obtained, these data may provide new information for the in vivo kinematics of the cervical spine.
The human femur is in a relatively complex mechanical environment, subject to the combined effects of multiple factors such as mechanical loads from movement and weight-bearing, as well as changes in the body fluid environment in daily life. In in vitro testing cases of the femur (e.g., testing of distal femoral fractures), changes in load conditions usually significantly affect the mechanical properties of the overall structure. However, there is currently no systematic evaluation standard for in vitro mechanical performance testing of the femur. Therefore, this paper established four human femur models (model A~model D) constructed based on computed tomography (CT) under different load environments, as well as two artificially synthesized femur models (the finite-element model and the experimental model) under the same load environment. Among them, for the human femur models, model A was configured to apply hip joint contact forces together with all muscle forces to approximate the real in vivo mechanical environment, model B was applied with hip joint contact force and abductor muscle force, model C was only applied with hip joint contact force, and model D was subjected to an equivalent resultant force. For the artificially synthesized femur models, both the finite-element model and the experimental model were applied with the same equivalent resultant force as model D. Comparative analyses revealed that model D exhibited femoral head displacement and stress-strain distributions similar to Model A, indicating its suitability as an equivalent in vitro test model. Further comparison between the finite-element and experimental synthetic femur models yielded consistent mechanical responses, thereby validating the equivalent model. In summary, it is hoped that the findings of this study will provide a reference for establishing a systematic, tiered preclinical evaluation system for hip prostheses/implants in the future.
Objective To investigate the sensitivity of 5 kinds of chemotherapeutic drugs on human colorectal cancer in vivo. Methods Xenografts in nude mice were set up by tumor tissues from 9 patients with colorectal cancer and nude mice were divided into 6 groups randomly， receiving saline （control group）， 5-fluorouracil （5-FU group）， doxorubicin（ADM group）， mitomycin （MMC group）， oxaliplatin （LOHP group）， and irinotecan （CPT-11 group）， respectively. The inhibitive rates （IR） of xenografts in 5 groups for each patient were calculated. Results The lowest and highest IR of 5 groups were 23.6% and 54.9% in 5-FU group， 23.7% and 69.5% in LOPH group， 23.6% and 82.6% in CPT-11group， 24.1% and 48.1% in MMC group， 5.8% and 20.7% in ADM group， respectively. The IR exceeded 40.0% in 7 patients of LOHP group， 6 patients of CPT-11 group， 4 patients of 5-FU group， and 1 patient of MMC group， respec-tively. Of 9 patients， the IR exceeded 40.0% to 3 kinds of drugs in 3 patients， to 2 kinds of drugs in 4 patients， the IR didn’t exceed 30.0% to 4 kinds of drug （IR was 82.6% to CPT-11） in 1 patient， and the IR didn’t exceed 31.0% to all 5 kinds of drugs in 1 patient. There were statistical differences on the IR of 5 kinds of drugs （H=24.061 2， P=0.000 1）. IR of ADM group was statistical lower than 5-FU group， MMC group， LOHP group， and CPT-11 group （P＜0.05），but there were no statistical differences between 5-FU group， MMC group， LOHP group， and CPT-11 group （P＞0.05）. Conclusions The xenografts from same patient have different sensitivity to different chemotherapy drugs， and the same chemotherapy drug corresponds to different IR in different patients. The IR of LOHP and CPT-11 are the highest， following by 5-FU and MMC.
ObjectiveTo review the research progress of in vivo bioreactor (IVB) for bone tissue engineering in order to provide reference for its future research direction.MethodsThe literature related to IVB used in bone tissue engineering in recent years was reviewed, and the principles of IVB construction, tissue types, sites, and methods of IVB construction, as well as the advantages of IVB used in bone tissue engineering were summarized.ResultsIVB takes advantage of the body’s ability to regenerate itself, using the body as a bioreactor to regenerate new tissues or organs at injured sites or at ectopic sites that can support the regeneration of new tissues. IVB can be constructed by tissue flap (subcutaneous pocket, muscle flap/pocket, fascia flap, periosteum flap, omentum flap/abdominal cavity) and axial vascular pedicle (axial vascular bundle, arteriovenous loop) alone or jointly. IVB is used to prefabricate vascularized tissue engineered bone that matched the shape and size of the defect. The prefabricated vascularized tissue engineered bone can be used as bone graft, pedicled bone flap, or free bone flap to repair bone defect. IVB solves the problem of insufficient vascularization in traditional bone tissue engineering to a certain extent.ConclusionIVB is a promising method for vascularized tissue engineered bone prefabrication and subsequent bone defect reconstruction, with unique advantages in the repair of large complex bone defects. However, the complexity of IVB construction and surgical complications hinder the clinical application of IVB. Researchers should aim to develop a simple, safe, and efficient IVB.
ObjectiveTo design a method for observing pulmonary microcirculation in vivo in a native tissue environment, due to the high incidence of lung diseases and the advantages of animal experiments in vivo.MethodsTen BALB/c male mice were randomly divided into group A and group B, with five mice in each group. A self-made apparatus was used to control the movement towards local lung tissues in order to get a stabilized observation plane, and then a 5-minute video was shot with laser confocal scanning microscope. During the filming, the mice in group A were injected with fluorescein isothiocyanate-dextran via the tail vein, and the mice in group B were injected with green fluorescent protein-platelets (extracted from the blood of tie2-cre&rosa26-tomato-EGFP transgenic black C57 male mice). The data of group A was used to observe the lungs perfusion and the damage to tissue by this method, and the data of group B was used to observe the movement of platelets.ResultsImage of lung structure obtained by this method was clear and stable. Mean areas of alveolus in an instant and at the 30th, 60th, 120th, 180th, and 300th second were (1 603±181), (1 588±183), (1 528±363), (1 506±353), (1 437±369), (1 549±307) μm2, respectively, and there were no significant differences between each time point (P>0.05). The video was smooth, the rapid movement of platelets was recorded and the particles were clear and without tailing; after the observation, hematoxylin-eosin staining showed no obvious damage to the lung tissue.ConclusionThe method can be used for the observation and research of the lung microcirculatory system in the living state of the mouse, and provides a methodological basis for studies of other lung diseases in vivo.
Near-infrared fluorescence imaging technology, which possesses superior advantages including real-time and fast imaging, high spatial and temporal resolution, and deep tissue penetration, shows great potential for tumor imaging in vivo and therapy. Ⅰ-Ⅲ-Ⅵ quantum dots exhibit high brightness, broad excitation, easily tunable emission wavelength and superior stability, and do not contain highly toxic heavy metal elements such as cadmium or lead. These advantages make Ⅰ-Ⅲ-Ⅵ quantum dots attract widespread attention in biomedical field. This review summarizes the recent advances in the controlled synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots and their applications in tumor imaging in vivo and therapy. Firstly, the organic-phase and aqueous-phase synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots as well as the strategies for regulating the near-infrared photoluminescence are briefly introduced; secondly, representative biomedical applications of near-infrared-emitting cadmium-free quantum dots including early diagnosis of tumor, lymphatic imaging, drug delivery, photothermal and photodynamic therapy are emphatically discussed; lastly, perspectives on the future directions of developing quantum dots for biomedical application and the faced challenges are discussed. This paper may provide guidance and reference for further research and clinical translation of cadmium-free quantum dots in tumor diagnosis and treatment.
ObjectiveTo review the researches of in vivo kinematics in lumbar degenerative spondylol isthesis (DS).
MethodsRelated literature concerning the in vivo kinematics in patients with lumbar DS was extensively reviewed and comprehensively analyzed in 4 terms of the instabil ity of lumbar DS, vertebral motion pattern, the morphological changes of spinal canal, and intraoperative biomechanical measurement.
ResultsWhether there is lumbar segmental instabil ity in lumbar DS patients is still controversial, which should be based on degenerative stage of lumbar spine and grade of slip. The hypomobility of the lumbar spinous processes and the facet joint is seen in DS. The diameter, cross-sectional area, and volume of spinal canal in lumbar DS patients are significantly smaller than those of the normal control. Because of its invasive procedure and medical ethics, the use of the intraoperative measurement device is limited. These reported researches of in vivo kinematics in DS are almost on the sagittal plane. However, few data have been reported on the 6-degree-of-freedom (6DOF) kinematics of the diseased levels under physiological loading conditions.
ConclusionThe 6DOF kinematics data can accurately reflect the segmental motion characteristics in lumbar DS patients, recent studies have been reported, further studies are still needed.
Objective
To review the in vivo imaging research progress of two-photon microscopy (TPM) in spinal cord.
Methods
The recent literature concerning in vivo two-photon imaging of axon, microglia, and calcium in transgenic mice spinal cord was extensively consulted and reviewed.
Results
In vivo two-photon imaging of spinal cord provide dynamic information about axonal degeneration and regeneration, microglial accumulation, and calcium influx after spinal cord injury.
Conclusion
TPM in vivo imaging study on spinal cord will provide theoretical foundation for pathophysiologic process of spinal cord injury.
