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Vascularized Bone-Mimetic Hydrogel Constructs by 3D Bioprinting to Promote Osteogenesis and Angiogenesis
Bone is a highly vascularized tissue with a unique and complex structure. Long bone consists of a peripheral cortical shell containing a network of channels for vascular penetration and an inner highly vascularized bone marrow space. Bioprinting is a powerful tool to enable rapid and precise spatial patterning of cells and biomaterials. Here we developed a two-step digital light processing technique to fabricate a bone-mimetic 3D hydrogel construct based on octacalcium phosphate (OCP), spheroids of human umbilical vein endothelial cells (HUVEC), and gelatin methacrylate (GelMA) hydrogels. The bone-mimetic 3D hydrogel construct was designed to consist of a peripheral OCP-containing GelMA ring to mimic the cortical shell, and a central GelMA ring containing HUVEC spheroids to mimic the bone marrow space. We further demonstrate that OCP, which is evenly embedded in the GelMA, stimulates the osteoblastic differentiation of mesenchymal stem cells. We refined the design of a spheroid culture device to facilitate the rapid formation of a large number of HUVEC spheroids, which were embedded into different concentrations of GelMA hydrogels. It is shown that the concentration of GelMA modulates the extent of formation of the capillary-like structures originating from the HUVEC spheroids. This cell-loaded hydrogel-based bone construct with a biomimetic dual ring structure can be potentially used for bone tissue engineering.
Journal Article
Rickety Stitch and the gelatinous Goo
\"Meet Rickety Stitch ... a walking, talking, singing skeleton minstrel. He's the one skeleton in the dungeon who seems to have retained his soul, and he has no idea why. His only clue to his former identity is a song he hears snippets of in his dreams, an epic bard's tale about the Road to Epoli and the land of Eem. His sidekick and sole friend is Goo, a squishy blob of jelly that Rickety alone can understand. Together they set out in search of Rickety's past, with abundant humor and adventure galore.\"--Inside jacket flap of Book 1.
Book
Use of Fluid Gelatin in Lumbar Spinal Stenosis Undergoing Unilateral Biportal Endoscopic: A Prospective, Randomized Controlled Trial
Objectives In patients with lumbar spinal stenosis (LSS) undergoing unilateral biportal endoscopic unilateral laminotomy for bilateral decompression (UBE‐ULBD), damage to the epidural venous plexus often leads to bleeding, increasing the risk of surgical complications. Surgiflo Hemostatic Matrix (SHM) is a gelatin extracted from porcine skin, used for intraoperative hemostasis. This study aims to evaluate the effectiveness and safety of using SHM during UBE‐ULBD surgery. Methods From October 2023 to July 2024, a total of 96 patients with LSS underwent UBE‐ULBD surgery. These 96 patients were randomly divided into two groups: the SHM group (48 patients, using flowable gelatin) and the non‐SHM group (48 patients, not using flowable gelatin). The primary outcomes included intraoperative blood loss, postoperative drainage volume, and the 3‐min hemostasis success rate. Secondary outcomes included symptomatic postoperative epidural hematoma (SPEH), surgical time, postoperative hospital stay, hospitalization costs, and complications. We used independent sample t‐tests to compare continuous data, and chi‐square tests or Fisher's exact tests to analyze categorical data. Results The intraoperative blood loss and postoperative drainage volume in the SHM group were significantly less than those in the non‐SHM group (p < 0.05), and the 3‐min hemostasis success rate in the SHM group was significantly higher than that in the non‐SHM group (p < 0.05). There were no statistically significant differences between the two groups regarding SPEH, postoperative hospital stay, hospitalization costs, and complications such as thrombosis formation and allergic reactions. However, the surgical time in the SHM group was significantly shorter than that in the non‐SHM group (p < 0.05). Conclusion When patients with LSS undergo UBE‐ULBD, the use of fluid gelatin can effectively reduce intraoperative and postoperative bleeding without introducing additional complications. The 96 patients were randomly assigned to two groups: the Surgiflo Hemostatic Matrix (SHM) group and the non‐SHM group. The use of fluid gelatin effectively reduces intraoperative and postoperative bleeding without leading to additional complications.
Journal Article
Development of chitosan-coated agar-gelatin particles for probiotic delivery and targeted release in the gastrointestinal tract
This study reports the development of a novel and simple formulation for probiotic delivery using chitosan-coated agar-gelatin gel particles. This methodology involves the production of agar-gelatin particles by thermally treating a mixture of agar and gelatin solutions at high temperatures (121 °C) and subsequently coating with chitosan. The particles were able to protect the probiotic strain Lactobacillus plantarum NCIMB 8826 during incubation for 2 h in simulated gastric fluid (pH 2), as no statistically significant loss (P > 0.05) in cell concentration was observed, and also resist dissolution in simulated intestinal fluid (pH 7.2). Interestingly, this protection is related to the fact that the intense thermal treatment affected the physicochemical properties of agars and resulted in the formation of a strong and tight polymer network, as indicated by the X-ray diffraction (XRD) analysis. Using an in vitro faecal batch fermentation model simulating the conditions of the distal part of the large intestine (pH 6.7–6.9), it was demonstrated by quantitative real-time PCR that the majority of L. plantarum cells were released from the agar-gelatin particles within 30 to 48 h. Overall, this work led to the development of a novel methodology for the production of probiotic-containing particles, which is simpler compared with current encapsulation technologies and has a lot of potential to be used for the controlled release of probiotics and potentially other solid bioactives in the large intestine.Key Points• Chitosan gel particles is a simple and scalable method of probiotic encapsulation.• Autoclaving agar-gelatin particles increases their stability at low pH.• Chitosan gel particles protected L. plantarum during gastrointestinal conditions.• Probiotics could be controlled release in the colon using chitosan gel particles.
Journal Article
Liquid-embedded (bio)printing of alginate-free, standalone, ultrafine, and ultrathin-walled cannular structures
While there has been considerable success in the three-dimensional bioprinting of relatively large standalone filamentous tissues, the fabrication of solid fibers with ultrafine diameters or those cannular featuring ultrathin walls remains a particular challenge. Here, an enabling strategy for (bio)printing of solid and hollow fibers whose size ranges could be facilely adjusted across a broad spectrum, is reported, using an aqueous two-phase embedded (bio)printing approach combined with specially designed cross-linking and extrusion methods. The generation of standalone, alginate-free aqueous architectures using this aqueous two-phase strategy allowed freeform patterning of aqueous bioinks, such as those composed of gelatin methacryloyl, within the immiscible aqueous support bath of poly(ethylene oxide). Our (bio)printing strategy revealed the fabrication of standalone solid or cannular structures with diameters as small as approximately 3 or 40 μm, respectively, and wall thicknesses of hollow conduits down to as thin as <5 μm. With cellular functions also demonstrated, we anticipate the methodology to serve as a platform that may satisfy the needs for the different types of potential biomedical and other applications in the future, especially those pertaining to cannular tissues of ultrasmall diameters and ultrathin walls used toward regenerative medicine and tissue model engineering.
Journal Article
A cost-effective measure to prevent hemorrhage in ultrasound-guided percutaneous liver biopsy
Background
Liver biopsy is a procedure whereby a biopsy needle is used to extract tissue from the liver parenchyma or focal lesions of the liver for pathological or microbiological examination. Percutaneous liver biopsy(PC-LB) is the most commonly employed and least expensive modality. However, it is associated with a significant risk of bleeding complications, which may potentially result in patient mortality. The objective of this study was to investigate the efficacy of Absorbable Gelatin Sponge sheet filler agent (AGS-SFA) in preventing bleeding complications during liver tissue biopsy and to validate a cost-effective surgical technique.
Methods
In this study, patients who underwent ultrasound-guided percutaneous liver tissue biopsy at our hospital were selected and randomly assigned to either an observation or control group. The observation group employed the use of AGS-SFA to fill the biopsy needle channel. Immediately following the biopsy procedure, the biopsy needle path was examined using Doppler ultrasound. The incidence of bleeding complications following biopsy and the associated factors influencing bleeding were analysed in the two groups.
Results
The observation and control groups were successfully biopsied, with a 100% success rate for both. The incidence of bleeding complications was significantly lower in the observation group than in the control group. Four factors, including fatty liver, prothrombin time, albumin and INR, were found to have a significant effect on biopsy bleeding in the control group.
Conclusion
The use of coaxial needles to inject AGS-SFA is an effective and economical procedure that significantly improves the safety of biopsy without increasing the burden of patient care.
Journal Article
Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair
Research over the past decade on the cell–biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications.
In gelMA hydrogels, the inherent bioactivity of gelatin is combined with the tailorability of photo-crosslinking.
3D-generated tissue analogs need to be geometrically natural mimics that are biofunctionally and mechanically stable.
GelMA will accelerate the development of cell-laden biofabricated constructs and will have a pioneering role in their translation to clinically relevant applications.
Journal Article
Cryoprotectant enables structural control of porous scaffolds for exploration of cellular mechano-responsiveness in 3D
Despite the wide applications, systematic mechanobiological investigation of 3D porous scaffolds has yet to be performed due to the lack of methodologies for decoupling the complex interplay between structural and mechanical properties. Here, we discover the regulatory effect of cryoprotectants on ice crystal growth and use this property to realize separate control of the scaffold pore size and stiffness. Fibroblasts and macrophages are sensitive to both structural and mechanical properties of the gelatin scaffolds, particularly to pore sizes. Interestingly, macrophages within smaller and softer pores exhibit pro-inflammatory phenotype, whereas anti-inflammatory phenotype is induced by larger and stiffer pores. The structure-regulated cellular mechano-responsiveness is attributed to the physical confinement caused by pores or osmotic pressure. Finally, in vivo stimulation of endogenous fibroblasts and macrophages by implanted scaffolds produce mechano-responses similar to the corresponding cells in vitro, indicating that the physical properties of scaffolds can be leveraged to modulate tissue regeneration.
Cellular responses to mechanical stimulation have emerged as an important area of research. Here, the authors use cryoprotectant to control the pore size and mechanical properties of porous scaffolds without changing the scaffold composition to allow for the study of cellular mechano-responsiveness in 3D.
Journal Article
Safety and efficacy of quick-soluble gelatin microparticles for transarterial embolization of the lower urinary tract: Preclinical study in a rabbit urinary bladder embolization model
Quick-soluble gelatin microparticles (QS-GMP) are emerging embolic agents under investigation for temporary vascular occlusion, offering reduced ischemic risk compared to permanent materials. The aim of this preclinical study was to evaluate the safety and efficacy of QS-GMP for transarterial embolization in a rabbit model of urinary bladder embolization. Twelve male New Zealand White rabbits underwent bilateral umbilical artery embolization using QS-GMP. Animals were assigned to four time-points (immediately, 3, 7, and 14 days post-embolization), with comprehensive assessments including clinical observations, hematologic and serum biochemical analysis, angiography, and histopathology. The procedure was technically feasible in all animals without intraoperative complications. Temporary hematuria and a transient decrease in body weight were observed post-procedure, both of which resolved spontaneously. Complete occlusion of the cranial vesical artery and absence of bladder wall perfusion were achieved immediately after embolization, followed by full recanalization at 3 days. Angiographic imaging at 7 and 14 days revealed transient hypervascularization of the bladder wall. Histopathological analysis showed marked edema, epithelial necrosis, and inflammatory infiltration at 3 and 7 days, with full urothelial regeneration observed at 14 days. No signs of ureteral or renal injury, or adverse systemic responses were detected. These findings suggest that QS-GMP may serve as a feasible option for temporary arterial occlusion in future veterinary lower urinary tract applications, although further long-term evaluation is warranted.
Journal Article