Mechanisms of Gynostemma pentaphyllum against non-alcoholic fibre liver disease based on network pharmacology and molecular docking.

As a progressive chronic disease, the effective treatment for non-alcoholic fibre liver disease (NAFLD) has not yet been thoroughly explored at the moment. The widespread use of Gynostemma pentaphyllum (Thunb) for its anti-insulin resistance effect indicates that potential therapeutic value may be found in Thunb for NAFLD. Hence, this research aims to discover the latent mechanism of Thunb for NAFLD treatment. To achieve the goal of discovering the latent mechanism of Thunb for NAFLD treatment, molecular docking strategy integrated a network phamacology was adopted in the exploration. We acquire Thunb compounds with activeness from TCMSP database. We collect the putative targets of Thunb and NAFLD to generate the network. Key targets and mechanism are screened by PPI analysis, GO and KEGG pathway enrichment analyses. Molecular docking simulation is introduced into the study as assessment method. Through network analysis and virtual screening based on molecular docking, 2 targets (AKT 1 and GSK3B) are identified as key therapeutic targets with satisfying binding affinity. Main mechanism is believed to be the biological process and pathway related to insulin resistance according to the enrichment analyses outcomes. Particularly, the P13K-AKT signalling pathway is recognized as a key pathway of the mechanism. In conclusion, the study shows that Thunb could be a potential treatment against NAFLD and may suppress insulin resistance through the P13K-AKT signalling pathway. The result of the exploration provides a novel perspective for approaching experimental exploration.

Photopolymerizable Biomaterials and Light-Based 3D Printing Strategies for Biomedical Applications.

Since the advent of additive manufacturing, known commonly as 3D printing, this technology has revolutionized the biofabrication landscape and driven numerous pivotal advancements in tissue engineering and regenerative medicine. Many 3D printing methods were developed in short course after Charles Hull first introduced the power of stereolithography to the world. However, materials development was not met with the same enthusiasm and remained the bottleneck in the field for some time. Only in the past decade has there been deliberate development to expand the materials toolbox for 3D printing applications to meet the true potential of 3D printing technologies. Herein, we review the development of biomaterials suited for light-based 3D printing modalities with an emphasis on bioprinting applications. We discuss the chemical mechanisms that govern photopolymerization and highlight the application of natural, synthetic, and composite biomaterials as 3D printed hydrogels. Because the quality of a 3D printed construct is highly dependent on both the material properties and processing technique, we included a final section on the theoretical and practical aspects behind light-based 3D printing as well as ways to employ that knowledge to troubleshoot and standardize the optimization of printing parameters.

The pharmacokinetic characteristics and excretion studies of fucosterol from Sargasssum fusiforme in rats.

Fucosterol is the main phytosterol in brown algae with various pharmacological effects such as cholesterol-lowering, anticancer, hepatoprotection and neuroprotection. Little is known about the pharmacokinetics and excretion characteristics of fucosterol. In this study, a GC-MS method was developed and validated for the determination of fucosterol in rat plasma, urine and feces. The method effectively avoids the interference of Δ5 -avenasterol, a cis-trans-isomer of fucosterol derived from feed, by using a TG-5 capillary column (a nonpolar column with 5% phenyl-methylpolysilicone as stationary phase material). The linearity ranges were fucosterol 0.300-18.0 µg/ml (R2 = 0.9960) for plasma, 0.0500-2.50 µg/ml for the urine sample (R2 = 0.9963) and 0.100-8.00 µg/mg (R2 = 0.9923) for the feces sample. With good extraction recoveries and stability, this rapid and sensitive method was successfully applied to the pharmacokinetic and excretion studies of fucosterol in Sprague-Dawley rats. Fucosterol from Sargassum fusiforme had poor absorption and slow elimination with an absolute oral bioavailability of 0.74%, and was mainly eliminated through fecal excretion.

Characteristic Volatile Composition of Seven Seaweeds from the Yellow Sea of China.

Plant volatile organic compounds (VOCs) represent a relatively wide class of secondary metabolites. The VOC profiles of seven seaweeds (Grateloupia filicina, Polysiphonia senticulosa, Callithamnion corymbosum, Sargassum thunbergii, Dictyota dichotoma, Enteromorpha prolifera and Ulva lactuca) from the Yellow Sea of China were investigated using multifiber headspace solid phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS), among them, the VOCs of three red algae Grateloupia filicina, Polysiphonia senticulosa, and Callithamnion corymbosum were first reported. Principal component analysis (PCA) was used to disclose characteristic categories and molecules of VOCs and network pharmacology was performed to predict potential biomedical utilization of candidate seaweeds. Aldehyde was found to be the most abundant VOC category in the present study and (E)-ß-ionone was the only compound found to exist in all seven seaweeds. The chemical diversity of aldehydes in E. prolifera suggest its potential application in chemotaxonomy and hinted that divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber is more suitable for aldehyde extraction. VOCs in D. dichotoma were characterized as sesquiterpenes and diterpenes and the most relevant pharmacological pathway was the neuroactive ligand-receptor interaction pathway, which suggests that D. dichotoma may have certain preventive and therapeutic values in cancer, especially in lung cancer, in addition to neuropsychiatric diseases.

3D printing of a biocompatible double network elastomer with digital control of mechanical properties.

The majority of 3D-printed biodegradable biomaterials are brittle, limiting their potential application to compliant tissues. Poly (glycerol sebacate) acrylate (PGSA) is a synthetic biodegradable and biocompatible elastomer, compatible with light-based 3D printing. In this work we employed digital-light-processing (DLP)-based 3D printing to create a complex PGSA network structure. Nature-inspired double network (DN) structures with two geometrically interconnected segments with different mechanical properties were printed from the same material in a single shot. Such capability has not been demonstrated by any other fabrication technique. The biocompatibility of PGSA after 3D printing was confirmed via cell-viability analysis. We used a finite element analysis (FEA) model to predict the failure of the DN structure under uniaxial tension. FEA confirmed the soft segments act as sacrificial elements while the hard segments retain structural integrity. The simulation demonstrated that the DN design absorbs 100% more energy before rupture than the network structure made by single exposure condition (SN), doubling the toughness of the overall structure. Using the FEA-informed design, a new DN structure was printed and the FEA predicted tensile test results agreed with tensile testing of the printed structure. This work demonstrated how geometrically-optimized material design can be easily and rapidly achieved by using DLP-based 3D printing, where well-defined patterns of different stiffnesses can be simultaneously formed using the same elastic biomaterial, and overall mechanical properties can be specifically optimized for different biomedical applications.

Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting.

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

A Comparable Study of CNN-Based Single Image Super-Resolution for Space-Based Imaging Sensors.

In the case of space-based space surveillance (SBSS), images of the target space objects captured by space-based imaging sensors usually suffer from low spatial resolution due to the extremely long distance between the target and the imaging sensor. Image super-resolution is an effective data processing operation to get informative high resolution images. In this paper, we comparably study four recent popular models for single image super-resolution based on convolutional neural networks (CNNs) with the purpose of space applications. We specially fine-tune the super-resolution models designed for natural images using simulated images of space objects, and test the performance of different CNN-based models in different conditions that are mainly considered for SBSS. Experimental results show the advantages and drawbacks of these models, which could be helpful for the choice of proper CNN-based super-resolution method to deal with image data of space objects.

Metal hypersensitivity in patient with posterior lumbar spine fusion: a case report and its literature review.

BACKGROUND: Metal hypersensitivity, mostly documented in prosthesis implantation, is a rare complication after arthroplasty. Such cases become rarer and more difficult to diagnose when it comes to lumbar surgery. CASE PRESENTATION: We present the case of a 52-year-old female patient with reoccured low back pain and sciatica after posterior lumbar decompression and fusion (PLDF) for her lumbar disc herniation. The initial clinical and radiological examinations showed no pathologies. Further imaging and histopathological studies in later period revealed an aseptic loosening of the hardware and an aseptic inflammatory response which was diagnosed to be metal hypersensitivity. To our knowledge, few allergic cases in the matter of spinal fusion were reported so far. CONCLUSIONS: Metal hypersensitivity after spinal fusion should be considered in patients with representation of postoperative back pain. And elaborate history taking would conduce a lot to it's diagnose.

Posterior short segment pedicle screw fixation and TLIF for the treatment of unstable thoracolumbar/lumbar fracture.

BACKGROUND: Currently, Posterior Short Segment Pedicle Screw Fixation is a popular procedure for treating unstable thoracolumbar/lumbar burst fracture. But progressive kyphosis and a high rate of hardware failure because of lack of the anterior column support remains a concern. The efficacy of different methods remains debatable and each technique has its advantages and disadvantages. METHODS: A consecutive series of 20 patients with isolated thoracolumbar/lumbar burst fractures were treated by posterior short segment pedicle screw fixation and transforaminal thoracolumbar/lumbar interbody fusion (TLIF) between January 2005 and December 2007. All patients were followed up for a minimum of 2 years. Demographic data, neurologic status, anterior vertebral body heights, segmental Cobb angle and treatment-related complications were evaluated. RESULTS: The mean operative time was 167 minutes (range, 150-220). Blood loss was 450 ~ 1200 ml, an average of 820 ml. All patients recovered with solid fusion of the intervertebral bone graft, without main complications like misplacement of the pedicle screw, nerve or vessel lesion or hard ware failure. The post-operative radiographs demonstrated a good fracture reduction and it was well maintained until the bone graft fusion. Neurological recovery of one to three Frankel grade was seen in 14 patients with partial neurological deficit, three grades of improvement was seen in one patient, two grades of improvement was observed in 6 patients and one grade of improvement was found in 6 patients. All the 6 patients with no paraplegia on admission remained neurological intact, and in one patient with Frankel D on admission no improvement was observed. CONCLUSION: Posterior short-segment pedicle fixation in conjunction with TLIF seems to be a feasible option in the management of selected thoracolumbar/lumbar burst fractures, thereby addressing all the three columns through a single approach with less trauma and good results.

The impact of dietary fibers on the construction and molecular network of extrusion-based 3D-printed chicken noodles: Unlocking the potential of specialized functional food.

3D printing technology is promising in creating specialized functional foods, such as high-protein and high dietary fiber noodles. In this study, chicken breast-based noodles with varying proportions of oat bran and konjac flour were developed. The research analyzed the physicochemical, digestive properties, and 3D printability of these chicken-based doughs and noodles. The results indicated that the inclusion of fiber-rich flours notably enhanced dough viscosity and viscoelasticity. However, exceeding 4 % konjac flour negatively affected cooking quality and texture due to its strong water absorption capacity. The experimental group with fiber-rich flours exhibited prolonged starch/protein digestion time compared to the Control group. The increased ability to bind water in the fiber rich formula likely restricted water mobility, affecting mass transition in the "water channel". Notably, chicken noodles fortified with 6 % oat bran and 2 % konjac flour displayed the highest 3D printability. These results offer valuable insights for the industry in selecting appropriate dietary fiber sources for the development of nutritionally balanced 3D-printed meal options.

Investigation of the spatial effects on PM2.5 in relation to land use and ecological restoration in urban agglomerations.

Heavy pollution of particulate matter with an aerodynamic diameter of <2.5 µm (PM2.5) poses increasing threats to the living environment worldwide. Urban agglomerations often lead to regional rather than local air pollution problems. This study explored the underlying global and local spatial driving mechanisms of PM2.5 variations of the 195 county-level administrative units in the urban agglomeration in the middle reaches of the Yangtze River, China, in 2020, using the global spatial regression and geographically weighted regression methods. Results showed that (1) at the county level, there were spatial variations of PM2.5, fluctuating from 20.1263 µg/m3 to 44.8416 µg/m3. (2) The concentrations of PM2.5 presented a positive spatial autocorrelation with a remarkable direct spatial spillover effect. (3) Forestland, grassland, elevation and ecological restoration were negatively correlated with PM2.5 concentrations, the indirect spatial spillover effect of elevation was noticeable. (4) The indirect reduction effects of ecological restoration on PM2.5 concentrations were substantial in the Wuhan urban agglomeration. (5) The reduction effect of forestland, grassland, ecological restoration and elevation on PM2.5 showed a noticeable spatial heterogeneity. In the future, it is suggested regional variability and the spatial spillover effect of air pollution be taken into account in environmental governance. Simultaneously, utilization of the mitigation effect of ecological restoration on PM2.5 is anticipated for the concerted effort in air pollution governance.

Protein and protein-polysaccharide composites-based 3D printing: The properties, roles and opportunities in future functional foods.

The food industry is undergoing a significant transformation with the advancement of 3D technology. Researchers in the field are increasingly interested in using protein and protein-polysaccharide composite materials for 3D printing applications. However, maintaining nutritional and sensory properties while guaranteeing printability of these materials is challenging. This review examines the commonly used protein and composite materials in food 3D printing and their roles in printing inks. This review also outlines the essential properties required for 3D printing, including extrudability, appropriate viscoelasticity, thixotropic properties, and gelation properties. Furthermore, it explores the wide range of potential applications for 3D printing technology in novel functional foods such as space food, dysphagia food, kid's food, meat analogue, and other specialized food products.

Nonocclusive mesenteric ischemia after percutaneous kyphoplasty: A case report.

RATIONALE: Percutaneous kyphoplasty (PKP) is a minimally invasive technique employed for treating vertebral compression fractures. Although PKP is simple and relatively safe, severe complications are possible. Here, we report a new, severe complication linked to this procedure, namely nonocclusive mesenteric ischemia (NOMI). PATIENT CONCERNS: An 83-year-old female patient, previously in good health, fell backward, landing on her buttocks, and subsequently experienced persistent low-back pain that exacerbated during turning or sitting up. DIAGNOSES: Lumbar spine radiography revealed wedge deformity of the L1 vertebral body. Lumbar spine magnetic resonance imaging indicated a fresh compression fracture of the L1 vertebral body. INTERVENTIONS: On the 2nd day following the trauma, the patient underwent PKP under local anesthesia. Anesthesia was satisfactory, and the procedure progressed smoothly. OUTCOMES: The patient experienced mild discomfort in the right abdomen within the 1st hour to 3 days postoperatively, mild abdominal distension on the 4th day, and sudden severe abdominal pain on the 5th day. Immediate abdominal computed tomography revealed ischemic changes in the ascending colon and hepatic flexure, accompanied by hepatic portal venous gas. An hour later, abdominal pain spontaneously subsided. Approximately 5 hours later, an enhanced abdominal computed tomography revealed no filling defects in the mesenteric vasculature, absence of luminal narrowing or occlusion, enhanced intestinal walls, and a notable improvement in hepatic portal venous gas. Considering NOMI and ischemia related to superior mesenteric artery spasm, vasodilator therapy (papaverine hydrochloride) was initiated, leading to favorable outcomes. On day 17, pathological examination of the hepatic flexure revealed moderate, acute, and chronic mucosal inflammation, along with interstitial fibrous tissue proliferation, providing clear evidence supporting ischemic changes. She was discharged on day 18 after a successful recovery. LESSONS: The occurrence of NOMI after PKP is uncommon. Yet, once it happens, delayed diagnosis or misdiagnosis can lead to serious consequences such as intestinal necrosis and abdominal infection, even endangering the patient's life. We currently lack experience in preventing this complication, but timely diagnosis and appropriate intervention are effective measures in treating such complications.

[Hemilateral bone longitudinal transport technique for the treatment of hemilateral defects of long bones of lower limbs].

OBJECTIVE: To explore clinical efficacy of Ilizarov hemilateral bone longitudinal transport technique in treating hemilateral bone defects associated with chronic osteomyelitis of lower extremity long bones. METHODS: Clinical data of 13 patients with hemilateral bone defects caused by chronic osteomyelitis of lower extremity long bones and treated by Ilizarov hemilateral bone longitudinal transport technique were retrospective analyzed, including 10 males and 3 female, aged from 14 to 55 years old;4 patients occurred femoral and 9 patients occurred tibial;10 patients were diagnosed as traumatic osteomyelitis and 3 patients as hematogenous osteomyelitis. The anatomical classification of Cierny-Mader in 13 patients was type Ⅲ. Bone and wound healing, postopertaive complication, and bony and functional results were observed by Paley evaluation standard. RESULTS: After removing external fixator, all patients were followed up from 6 to 70 months. Transporting time ranged from 54 to 158 d. And the time in external fixation ranged from 6.8 to 19.5 months. External fixation index (EFI) ranged from 1.23 to 1.6 months/cm. According to Paley's evaluation criteria, bony results were excellent in 13 patients;functional results showed excellent in 12 patients and good in 1 patient. Two patients occurred poor union on the docking sites and healed with autogenous iliac bone graft. The callus at the extended area was poorly mineralized and improved significantly when treated with low-intensity pulsed ultrasound in one patient. All patients had good wound healing without recurrence of osteomyelitis and refracture. There was no vascular and nerve injury and axial deviation in all patients and they were satisfied with the appearance and function of lower limbs. The range of motion of knee and ankle joint before operation was 120 ° to 150 ° and 35 °to 80 ° respectively, and at the latest follow-up was 110 ° to 140 ° and 30 ° to 75 ° . CONCLUSION: Ilizarov hemilateral bone longitudinal transport technique is effective in treating infective hemilateral bone defects of lower extremity long bones, which could not only simplify architecture of external fixation, but also reduce the number of fixation pins, shorten the time in external fixator and decrease the incidence of pin tract infection. However, this technique is highly demanding, and the growth of callus in extended region and healing of bone apposition should be noticed.

[Effect of cotton-moxibustion on chronic eczema and quality of life].

OBJECTIVE: To compare the therapeutic effect between cotton-moxibustion and compound flumetasone ointment, and observe the effect on quality of life in patients with chronic eczema. METHODS: A total of 66 patients with chronic eczema were randomized into an observation group (33 cases, 2 cases dropped off) and a control group (33 cases, 2 cases dropped off). In the observation group, cotton-moxibustion was adopted on target skin lesion, once a day, 3 cones a time. In the control group, external application of compound flumetasone ointment was given twice a day. The treatment for 3 weeks was required in the both groups. Before treatment and 1,2,3 weeks into treatment, scores of visual analogue scale (VAS), eczema area and severity index (EASI) and dermatology life quality index (DLQI) were observed, and the recurrence rate was evaluated in the follow-up one month after treatment. RESULTS: Compared before treatment, the VAS scores of 1,2,3 weeks into treatment, the EASI and DLQI scores of 2,3 weeks into treatment were decreased in the both groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). The follow-up recurrence rate in the observation group were lower than the control group (P<0.05). CONCLUSION: Cotton-moxibustion can effectively improve the pruritus symptom, skin lesion and quality of life in the patients with chronic eczema, the therapeutic effect is superior to the external application of compound flumetasone ointment.

Rapid bioprinting of conjunctival stem cell micro-constructs for subconjunctival ocular injection.

Ocular surface diseases including conjunctival disorders are multifactorial progressive conditions that can severely affect vision and quality of life. In recent years, stem cell therapies based on conjunctival stem cells (CjSCs) have become a potential solution for treating ocular surface diseases. However, neither an efficient culture of CjSCs nor the development of a minimally invasive ocular surface CjSC transplantation therapy has been reported. Here, we developed a robust in vitro expansion method for primary rabbit-derived CjSCs and applied digital light processing (DLP)-based bioprinting to produce CjSC-loaded hydrogel micro-constructs for injectable delivery. Expansion medium containing small molecule cocktail generated fast dividing and highly homogenous CjSCs for more than 10 passages in feeder-free culture. Bioprinted hydrogel micro-constructs with tunable mechanical properties enabled the 3D culture of CjSCs while supporting viability, stem cell phenotype, and differentiation potency into conjunctival goblet cells. These hydrogel micro-constructs were well-suited for scalable dynamic suspension culture of CjSCs and were successfully delivered to the bulbar conjunctival epithelium via minimally invasive subconjunctival injection. This work integrates novel cell culture strategies with bioprinting to develop a clinically relevant injectable-delivery approach for CjSCs towards the stem cell therapies for the treatment of ocular surface diseases.

Controlled Growth Factor Release in 3D-Printed Hydrogels.

Growth factors (GFs) are critical components in governing cell fate during tissue regeneration. Their controlled delivery is challenging due to rapid turnover rates in vivo. Functionalized hydrogels, such as heparin-based hydrogels, have demonstrated great potential in regulating GF release. While the retention effects of various concentrations and molecular weights of heparin have been investigated, the role of geometry is unknown. In this work, 3D printing is used to fabricate GF-embedded heparin-based hydrogels with arbitrarily complex geometry (i.e., teabag, flower shapes). Simplified cylindrical core-shell structures with varied shell thickness are printed, and the rates of GF release are measured over the course of 28 days. Increasing the shell layers' thickness decreases the rate of GF release. Additionally, a mathematical model is developed, which is found capable of accurately predicting GF release kinetics in hydrogels with shell layers greater than 0.5 mm thick (R2 > 0.96). Finally, the sequential release is demonstrated by printing two GFs in alternating radial layers. By switching the spatial order, the delivery sequence of the GFs can be modulated. This study demonstrates how 3D printing can be utilized to fabricate user-defined structures with unique geometry in order to control the rate of GF release in hydrogels.

Real-time measurements of black carbon and other pollutant emissions from residential biofuel stoves in rural China.

Biofuel stoves are an important source of black carbon (BC) emissions, which have adverse effects on the environment and human health, especially in rural areas. However, there have been only limited studies of BC emissions from residential biofuel stoves based on real-time measurements. In this study, a photo-acoustic extinctiometer (PAX)-based real-time measurement system was employed to monitor the emission characteristics of corncobs, corn stalks, cotton stalks and poplar branches in simple or improved stoves (with a total of 16 units) in Hebei Province, China. The real-time and phased emissions of BC, fine particulate matter (PM2.5), carbon monoxide (CO) and carbon dioxide (CO2) were assessed, and the effects of stove type and fuel on emissions were analyzed. Under the same conditions, polar branches were associated with the highest BC emission factors (EFs) of up to 2.64 ± 0.42 g kg-1, while the EFs for improved stoves were higher than those for simple stoves. During the ignition phase, BC emissions were found to be low, while the later addition of fuel dramatically increased emissions, followed by a gradual decrease until the next fuel addition. The phased results show that the flaming phase had the highest BC emission rate, the fuel addition phase was associated with the highest BC EF. The BC emission rates and EFs for the ignition, fuel addition, flaming and smoldering phases ranged from 0.0014-0.014, 0.11-6.32, 0.18-2.24 and 0.03-0.32 mg s-1, and from 0.04-0.18, 0.38-9.53, 0.45-3.55 and 0.12-1.01 g kg-1, respectively. This study assessed the BC emissions from residential biofuel stoves using a larger sample size than in prior work. The results increase our understanding of the BC emissions process, which is helpful in terms of improving the accuracy of BC EF estimations. The real-time measurement process described herein is also expected to provide new approaches to minimizing BC emissions.

A sequential 3D bioprinting and orthogonal bioconjugation approach for precision tissue engineering.

Recent advances in 3D bioprinting have transformed the tissue engineering landscape by enabling the controlled placement of cells, biomaterials, and bioactive agents for the biofabrication of living tissues and organs. However, the application of 3D bioprinting is limited by the availability of cytocompatible and printable biomaterials that recapitulate properties of native tissues. Here, we developed an integrated 3D projection bioprinting and orthogonal photoconjugation platform for precision tissue engineering of tailored microenvironments. By using a photoreactive thiol-ene gelatin bioink, soft hydrogels can be bioprinted into complex geometries and photopatterned with bioactive moieties in a rapid and scalable manner via digital light projection (DLP) technology. This enables localized modulation of biophysical properties such as stiffness and microarchitecture as well as precise control over spatial distribution and concentration of immobilized functional groups. As such, well-defined properties can be directly incorporated using a single platform to produce desired tissue-specific functions within bioprinted constructs. We demonstrated high viability of encapsulated endothelial cells and human cardiomyocytes using our dual process and fabricated tissue constructs functionalized with VEGF peptide mimics to induce guided endothelial cell growth for programmable vascularization. This work represents a pivotal step in engineering multifunctional constructs with unprecedented control, precision, and versatility for the rational design of biomimetic tissues.

Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions.

Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.