ObjectiveTo explore the feasibility of three-dimensional (3D) bioprinted adipose-derived stem cells (ADSCs) combined with gelatin methacryloyl (GelMA) to construct tissue engineered cartilage.MethodsAdipose tissue voluntarily donated by liposuction patients was collected to isolate and culture human ADSCs (hADSCs). The third generation cells were mixed with GelMA hydrogel and photoinitiator to make biological ink. The hADSCs-GelMA composite scaffold was prepared by 3D bioprinting technology, and it was observed in general, and observed by scanning electron microscope after cultured for 1 day and chondrogenic induction culture for 14 days. After cultured for 1, 4, and 7 days, the composite scaffolds were taken for live/dead cell staining to observe cell survival rate; and cell counting kit 8 (CCK-8) method was used to detect cell proliferation. The composite scaffold samples cultured in cartilage induction for 14 days were taken as the experimental group, and the composite scaffolds cultured in complete medium for 14 days were used as the control group. Real-time fluorescent quantitative PCR (qRT-PCR) was performed to detect cartilage formation. The relative expression levels of the mRNA of cartilage matrix gene [(aggrecan, ACAN)], chondrogenic regulatory factor (SOX9), cartilage-specific gene [collagen type Ⅱ A1 (COLⅡA1)], and cartilage hypertrophy marker gene [collagen type ⅩA1 (COLⅩA1)] were detected. The 3D bioprinted hADSCs-GelMA composite scaffold (experimental group) and the blank GelMA hydrogel scaffold without cells (control group) cultured for 14 days of chondrogenesis were implanted into the subcutaneous pockets of the back of nude mice respectively, and the materials were taken after 4 weeks, and gross observation, Safranin O staining, Alcian blue staining, and collagen type Ⅱ immunohistochemical staining were performed to observe the cartilage formation in the composite scaffold.ResultsMacroscope and scanning electron microscope observations showed that the hADSCs-GelMA composite scaffolds had a stable and regular structure. The cell viability could be maintained at 80%-90% at 1, 4, and 7 days after printing, and the differences between different time points were significant (P<0.05). The results of CCK-8 experiment showed that the cells in the scaffold showed continuous proliferation after printing. After 14 days of chondrogenic induction and culture on the composite scaffold, the expressions of ACAN, SOX9, and COLⅡA1 were significantly up-regulated (P<0.05), the expression of COLⅩA1 was significantly down-regulated (P<0.05). The scaffold was taken out at 4 weeks after implantation. The structure of the scaffold was complete and clear. Histological and immunohistochemical results showed that cartilage matrix and collagen type Ⅱ were deposited, and there was cartilage lacuna formation, which confirmed the formation of cartilage tissue.ConclusionThe 3D bioprinted hADSCs-GelMA composite scaffold has a stable 3D structure and high cell viability, and can be induced differentiation into cartilage tissue, which can be used to construct tissue engineered cartilage in vivo and in vitro.
Objective To review the research progress of in-situ three dimensional (3D) bio-printing technology in the repair of bone and cartilage injuries. Methods Literature on the application of in-situ 3D bio-printing technology to repair bone and cartilage injuries at home and abroad in recent years was reviewed, analyzed, and summarized. Results As a new tissue engineering technology, in-situ 3D bio-printing technology is mainly applied to repair bone, cartilage, and skin tissue injuries. By combining biomaterials, bioactive substances, and cells, tissue is printed directly at the site of injury or defect. At present, the research on the technology mainly focuses on printing mode, bio-ink, and printing technology; the application research in the field of bone and cartilage mainly focuses on pre-vascularization, adjusting the composition of bio-ink, improving scaffold structure, printing technology, loading drugs, cells, and bioactive factors, so as to promote tissue injury repair. Conclusion Multiple animal experiments have confirmed that in-situ 3D bio-printing technology can construct bone and cartilage tissue grafts in a real-time, rapid, and minimally invasive manner. In the future, it is necessary to continue to develop bio-inks suitable for specific tissue grafts, as well as combine with robotics, fusion imaging, and computer-aided medicine to improve printing efficiency.
The β-secretase is one of prospective targets against Alzheimer's disease (AD). A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of Hydroethylamines (HEAs) as β-secretase inhibitors was established using Topomer CoMFA. The multiple correlation coefficient of fitting, cross validation and external validation were r2=0.928, qloo2=0.605 and rpred2=0.626, respectively. The 3D-QSAR model was used to search R groups from ZINC database as the source of structural fragments. As a result, a series of R groups with relatively high activity contribution was obtained to design a total of 15 new compounds, with higher activity than that of the template molecule. The molecular docking was employed to study the interaction mode between the new compounds as ligands and β-secretase as receptors, displaying that hydrogen bond and hydrophobicity played important roles in the binding affinity between the new compounds and β-secretase. The results showed that Topomer CoMFA and Topomer Search could be effectively used to screen and design new molecules of HEAs as β-secretase inhibitors, and the designed compounds could provide new candidates for drug design targeting AD.
Three-dimensional (3D) printing is a low-cost, high-efficiency production method, which can reduce the current cost and increase the profitability of skin repair material industry nowadays, and develop products with better performance. The 3D printing technology commonly used in the preparation of skin repair materials includes fused deposition molding technology and 3D bioprinting technology. Fused deposition molding technology has the advantages of simple and light equipment, but insufficient material selection. 3D bioprinting technology has more materials to choose from, but the equipment is cumbersome and expensive. In recent years, research on both technologies has focused on the development and application of materials. This article details the principles of fused deposition modeling and 3D bioprinting, research advances in wound dressings and tissue engineering skin production, and future developments in 3D printing on skin tissue repair, including cosmetic restoration and biomimetic tissue engineering. Also, this review prospects the development of 3D printing technology in skin tissue repairment.
A method of ultrasonic simulation based on the FIELD II software platform for carotid artery plaque was proposed according to the analysis for geometrical shape, tissue characteristics and acoustic properties of carotid artery plaques in clinic, and then a simulation system was developed by using the MATLAB graphical user interface (GUI). In the simulation and development, a three-dimensional geometric model of blood vessel with plaques was set up by using the metaball implicit surface technique, and a tissue model was established based on the scatterers with spatial position of gamma random distribution. Comparison of the statistical and geometrical characteristics from simulated ultrasound B-mode images with those based on clinical ones and preset values, the results fully demonstrated the effectiveness of the simulation methods and system.
Objective To explore the effectiveness of computer-aided technology in the treatment of primary elbow osteoarthritis combined with stiffness under arthroscopy. Methods The clinical data of 32 patients with primary elbow osteoarthritis combined with stiffness between June 2018 and December 2020 were retrospectively analyzed. There were 22 males and 10 females with an average age of 53.4 years (range, 31-71 years). X-ray film and three-dimensional CT examinations showed osteophytes of varying degrees in the elbow joint. Loose bodies existed in 16 cases, and there were 7 cases combined with ulnar nerve entrapment syndrome. The median symptom duration was 2.5 years (range, 3 months to 22.5 years). The location of bone impingement from 0° extension to 140° flexion of the elbow joint was simulated by computer-aided technology before operation and a three-dimensional printed model was used to visualize the amount and scope of impinging osteophytes removal from the anterior and posterior elbow joint to accurately guide the operation. Meanwhile, the effect of elbow joint release and impinging osteophytes removal was examined visually under arthroscopy. The visual analogue scale (VAS) score, Mayo elbow performance score (MEPS), and elbow range of motion (extension, flexion, extension and flexion) were compared between before and after operation to evaluate elbow function. Results The mean operation time was 108 minutes (range, 50-160 minutes). All 32 patients were followed up 9-18 months with an average of 12.5 months. There was no other complication such as infection, nervous system injury, joint cavity effusion, and heterotopic ossification, except 2 cases with postoperative joint contracture at 3 weeks after operation due to the failure to persist in regular functional exercises. Loose bodies of elbow and impinging osteophytes were removed completely for all patients, and functional recovery was satisfactory. At last follow-up, VAS score, MEPS score, extension, flexion, flexion and extension range of motion significantly improved when compared with preoperative ones (P<0.05). Conclusion Arthroscopic treatment of primary elbow osteoarthritis combined with stiffness using computer-aided technology can significantly reduce pain, achieve satisfactory functional recovery and reliable effectiveness.
ObjectiveTo investigate the accuracy of progressive three-dimensional navigation template system (abbreviated as progressive template) to assist atlas-axial pedicle screw placement. MethodsThe clinical data of 33 patients with atlas-axial posterior internal fixation surgery between May 2015 and May 2017 were retrospectively analyzed. According to the different methods of auxiliary screw placement, the patients were divided into trial group (19 cases, screw placement assisted by progressive template) and control group (14 cases, screw placement assisted by single navigation template system, abbreviated as initial navigation template). There was no significant difference in gender, age, cause of injury, damage segments, damage types, and preoperative Frankel classification between the two groups (P>0.05). The operation time and intraoperative blood loss of the two groups were compared. The safety of screw placement was evaluated on postoperative CT by using the method from Kawaguchi et al, the deviation of screw insertion point were calculated, the angular deviation of the nailing on coordinate systems XOZ, XOY, YOZ were calculated according to Peng’s method. ResultsAll patients completed the operation successfully; the operation time and intraoperative blood loss in the trial group were significantly less than those in the control group (t=–2.360, P=0.022; t=–3.006, P=0.004). All patients were followed up 12–40 months (mean, 25.3 months). There was no significant vascular injury or nerve injury aggravation. Postoperative immediate X-ray film and CT showed the dislocation was corrected. Postoperative immediate CT showed that all 76 screws were of grade 0 in the trial group, and the safety of screw placement was 100%; 51 screws were of grade 0, 3 of gradeⅠ, and 2 of gradeⅡ in the control group, and the safety of screw placement was 91.1%; there was significant difference in safety of screw placement between the two groups (χ2=7.050, P=0.030). The screw insertion point deviation and angular deviation of the nailing on XOY and YOZ planes in the trial group were significantly less than those in the control group (P<0.05). There was no significant difference in angular deviation of the nailing on XOZ between the two groups (t=1.060, P=0.290). ConclusionCompared with the initial navigation template, the progressive navigation template assisting atlas-axial pedicle screw placement to treat atlas-axial fracture with dislocation, can reduce operation time and intraoperative blood loss, improve the safety of screw placement, and match the preoperative design more accurately.
Objective To study the hook of hamate bone by anatomy and iconography methods in order to provide information for the cl inical treatment of injuries to the hook of hamate bone and the deep branch of ulnar nerve. Methods Fifty-two upper l imb specimens of adult corpses contributed voluntarily were collected, including 40 antisepticized old specimens and 12 fresh ones. The hook of hamate bone and its adjacent structure were observed. Twentyfour upper l imbs selected randomly from specimens of corpses and 24 upper l imbs from 12 healthy adults were investigated by computed tomography (CT) three-dimensional reconstruction, and then related data were measured. The measurement results of24 specimens were analyzed statistically. Results The hook of hamate bone is an important component of ulnar carpal canal and carpal canal, and the deep branch of ulnar nerve is located closely in the inner front of the hook of hamate bone. The flexor tendons of the forth and the l ittle fingers are in the innermost side, closely l ie next to the outside of the hook of hamate bone. The hamate bone located between the capitate bone and the three-cornered bone with wedge-shaped. The medial-, lateral-, and front-sides are all facies articularis. The hook of hamate bone has an approximate shape of a flat plate. The position migrated from the body of the hamate bone, the middle of the hook and the enlargement of the top of the hook were given the names of “the basis of the hook”, “the waist of the hook”, and “the coronal of the hook”, respectively. The short path of the basement are all longer than the short path of the waist. The long path of the top of the hook is the maximum length diameter of the hook of hamate bone, and is longer than the long path of the basement and the long path of the waist. The iconography shape and trait of the hook of hamate bone is similar to the anatomy result. There were no statistically significant differences (P gt; 0.05) between two methods in the seven parameters as follows: the long path of the basement of the hook, the short path of the basement of the hook, the long path of the waist of thehook, the short path of the waist of the hook, the long path of the top of the hook, the height of the hook, of hamate bone, and the distance between the top and the waist of the hook. Conclusion The hook of hamate bone can be divided into three parts: the coronal part, the waist part, and the basal part; fracture of the hamate bone can be divided into fracture of the body, fracture of the hook, and fracture of the body and the hook. Facture of the hook of hamate bone or fracture unnion can easily result in injure of the deep branch of ulnar nerve and the flexor tendons of the forth and the l ittle fingers. The measurement results of CT threedimensional reconstruction can be used as reference value directly in cl inical treatments.
We developed a three-dimensional finite element model of the pelvis. According to Letournel methods, we established a pelvis model of T-shaped fracture with its three different fixation systems, i.e. double column reconstruction plates, anterior column plate combined with posterior column screws and anterior column plate combined with quadrilateral area screws. It was found that the pelvic model was effective and could be used to simulate the mechanical behavior of the pelvis. Three fixation systems had great therapeutic effect on the T-shaped fracture. All fixation systems could increase the stiffness of the model, decrease the stress concentration level and decrease the displacement difference along the fracture line. The quadrilateral area screws, which were drilled into cortical bone, could generate beneficial effect on the T-type fracture. Therefore, the third fixation system mentioned above (i.e. the anterior column plate combined with quadrilateral area screws) has the best biomechanical stability to the T-type fracture.
Objective To investigate the construction of a novel tissue engineered meniscus scaffold based on low temperature deposition three-dimenisonal (3D) printing technology and evaluate its biocompatibility. Methods The fresh pig meniscus was decellularized by improved physicochemical method to obtain decellularized meniscus matrix homogenate. Gross observation, HE staining, and DAPI staining were used to observe the decellularization effect. Toluidine blue staining, safranin O staining, and sirius red staining were used to evaluate the retention of mucopolysaccharide and collagen. Then, the decellularized meniscus matrix bioink was prepared, and the new tissue engineered meniscus scaffold was prepared by low temperature deposition 3D printing technology. Scanning electron microscopy was used to observe the microstructure. After co-culture with adipose-derived stem cells, the cell compatibility of the scaffolds was observed by cell counting kit 8 (CCK-8), and the cell activity and morphology were observed by dead/live cell staining and cytoskeleton staining. The inflammatory cell infiltration and degradation of the scaffolds were evaluated by subcutaneous experiment in rats. Results The decellularized meniscus matrix homogenate appeared as a transparent gel. DAPI and histological staining showed that the immunogenic nucleic acids were effectively removed and the active components of mucopolysaccharide and collagen were remained. The new tissue engineered meniscus scaffolds was constructed by low temperature deposition 3D printing technology and it had macroporous-microporous microstructures under scanning electron microscopy. CCK-8 test showed that the scaffolds had good cell compatibility. Dead/live cell staining showed that the scaffold could effectively maintain cell viability (>90%). Cytoskeleton staining showed that the scaffolds were benefit for cell adhesion and spreading. After 1 week of subcutaneous implantation of the scaffolds in rats, there was a mild inflammatory response, but no significant inflammatory response was observed after 3 weeks, and the scaffolds gradually degraded. Conclusion The novel tissue engineered meniscus scaffold constructed by low temperature deposition 3D printing technology has a graded macroporous-microporous microstructure and good cytocompatibility, which is conducive to cell adhesion and growth, laying the foundation for the in vivo research of tissue engineered meniscus scaffolds in the next step.