Drug testing in 3D cell cultures, such as spheroids, organoids, and bioprinted constructs, created from patient samples, enables pre-clinical assessment prior to patient treatment. These procedures enable the selection of the most fitting pharmaceutical agent for the individual. Furthermore, these options enable faster recovery for patients, because there is no time wasted while changing therapies. These models are suitable for both fundamental and practical research endeavors, given their treatment responses which closely resemble those of natural tissue. Subsequently, these methods, due to their affordability and ability to circumvent interspecies disparities, may replace animal models in the future. EX 527 This review scrutinizes the dynamic and evolving realm of toxicological testing and its implementations.
Three-dimensional (3D) printing offers the ability to create porous hydroxyapatite (HA) scaffolds with customized structures, leading to promising applications due to their excellent biocompatibility. Although possessing no antimicrobial capabilities, its broad usage is restricted. Through the digital light processing (DLP) method, a porous ceramic scaffold was developed in this research project. EX 527 The layer-by-layer technique was used to create multilayer chitosan/alginate composite coatings that were applied to scaffolds, with zinc ions incorporated via ionic crosslinking. The coatings' chemical composition and structural details were established via scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). EDS spectroscopy demonstrated a uniform dispersion of Zn2+ throughout the coating sample. Comparatively, coated scaffolds presented a marginally elevated compressive strength (1152.03 MPa) as opposed to the compressive strength of bare scaffolds (1042.056 MPa). The soaking experiment on the scaffolds indicated that the coated ones experienced a slower rate of degradation. The in vitro effect of zinc-enhanced coatings on cellular adhesion, proliferation, and differentiation is demonstrably positive, contingent on controlled concentration levels. Though Zn2+ over-release induced cytotoxicity, its antibacterial effectiveness was heightened against Escherichia coli (99.4%) and Staphylococcus aureus (93%).
A prevalent technique for speeding up bone regeneration is light-driven three-dimensional (3D) printing of hydrogels. However, the design methodologies of traditional hydrogels do not take into account the biomimetic regulation of different stages in bone healing, which prevents the resulting hydrogels from stimulating sufficient osteogenesis and correspondingly restricts their potential in facilitating bone regeneration. Progress in synthetic biology-based DNA hydrogels promises to innovate existing strategies, benefiting from attributes like resistance to enzymatic breakdown, adjustable properties, controlled structure, and exceptional mechanical resilience. Nevertheless, the 3D printing process for DNA hydrogels is not well-articulated, demonstrating various initial implementations. The early development of 3D DNA hydrogel printing, along with the potential implication of these hydrogel-based bone organoids for bone regeneration, is the focus of this article.
Multilayered biofunctional polymeric coatings are utilized for the surface modification of titanium alloy substrates via 3D printing. Polycaprolactone (PCL) and poly(lactic-co-glycolic) acid (PLGA) polymers were embedded with vancomycin (VA) for antibacterial activity and amorphous calcium phosphate (ACP) for osseointegration promotion, respectively. Uniform deposition of the ACP-laden formulation was observed on the PCL coatings, significantly enhancing cell adhesion on the titanium alloy substrates relative to the PLGA coatings. Scanning electron microscopy and Fourier-transform infrared spectroscopy jointly revealed a nanocomposite ACP particle structure exhibiting significant polymer interaction. Polymeric coatings exhibited comparable MC3T3 osteoblast proliferation rates, matching the control groups' results in viability assays. A comparative in vitro live/dead analysis of cell attachment to PCL coatings demonstrated a stronger cell adhesion on 10-layer coatings (experiencing a burst release of ACP) in contrast to 20-layer coatings (demonstrating a steady ACP release). Multilayered PCL coatings, loaded with the antibacterial drug VA, exhibited a tunable release kinetics profile, which depended on the drug content and coating structure. The coatings' release of active VA reached levels above the minimum inhibitory concentration and minimum bactericidal concentration, thus proving their effectiveness against the Staphylococcus aureus bacterial strain. Developing antibacterial, biocompatible coatings to encourage bone growth around orthopedic implants is facilitated by this research.
Bone defect repair and reconstruction pose significant unsolved problems for orthopedic practitioners. On the other hand, 3D-bioprinted active bone implants could provide a new and effective solution. Layer-by-layer 3D bioprinting was employed in this case to create personalized PCL/TCP/PRP active scaffolds, utilizing a bioink consisting of the patient's autologous platelet-rich plasma (PRP) combined with a polycaprolactone/tricalcium phosphate (PCL/TCP) composite scaffold material. A bone defect was repaired and rebuilt using a scaffold in the patient after the removal of a tibial tumor from the tibia. 3D-bioprinting allows for the creation of personalized active bone, which, in contrast to traditional bone implant materials, holds considerable clinical promise due to its biological activity, osteoinductivity, and individualization.
Regenerative medicine stands to benefit immensely from the persistent development of three-dimensional bioprinting technology, owing to its remarkable potential. Through the additive deposition of biochemical products, biological materials, and living cells, bioengineering produces structures. A multitude of bioprinting techniques and biomaterials, often referred to as bioinks, are available. The quality of these processes is directly proportionate to their rheological properties. CaCl2 was used as the ionic crosslinking agent to prepare alginate-based hydrogels in this study. A study of the rheological behavior was undertaken, coupled with simulations of bioprinting processes under specified conditions, aiming to establish possible relationships between rheological parameters and bioprinting variables. EX 527 The extrusion pressure demonstrated a clear linear dependence on the flow consistency index rheological parameter 'k', and correspondingly, the extrusion time displayed a clear linear dependence on the flow behavior index rheological parameter 'n'. Simplifying the repetitive processes currently used to optimize extrusion pressure and dispensing head displacement speed would reduce time and material usage, ultimately improving bioprinting outcomes.
Large-scale skin injuries are frequently associated with compromised wound healing, leading to scar tissue development, and substantial health issues and fatalities. The research seeks to explore the in vivo efficacy of 3D-printed tissue-engineered skin constructs, employing biomaterials loaded with human adipose-derived stem cells (hADSCs), in the context of wound healing. Decellularized adipose tissue, having its extracellular matrix components lyophilized and solubilized, yielded a pre-gel of adipose tissue decellularized extracellular matrix (dECM). This newly designed biomaterial's structure is derived from adipose tissue dECM pre-gel, methacrylated gelatin (GelMA), and methacrylated hyaluronic acid (HAMA). Rheological measurements were used to characterize the phase-transition temperature and the storage and loss modulus values measured at that temperature. By employing 3D printing, a skin substitute, reinforced with a supply of hADSCs, was fabricated through tissue engineering. Full-thickness skin wound healing models were established in nude mice, which were then randomly divided into four groups: (A) the full-thickness skin graft treatment group, (B) the experimental 3D-bioprinted skin substitute treatment group, (C) the microskin graft treatment group, and (D) the control group. 245.71 nanograms of DNA per milligram of dECM were observed, thereby satisfying the prevailing criteria for decellularization procedures. Adipose tissue dECM, solubilized and rendered thermo-sensitive, underwent a phase transition from sol to gel with rising temperatures. A phase transition from gel to sol takes place in the dECM-GelMA-HAMA precursor at 175°C, with a measured storage and loss modulus of approximately 8 Pa. Scanning electron microscopy identified a 3D porous network structure with appropriate porosity and pore size within the crosslinked dECM-GelMA-HAMA hydrogel. The skin substitute's shape is consistently stable, with its structure characterized by a regular grid pattern. Treatment with the 3D-printed skin substitute enhanced wound healing in the experimental animals by attenuating inflammation, increasing blood supply to the wound, and promoting the processes of re-epithelialization, collagen organization and deposition, and the growth of new blood vessels. Overall, a 3D-printed skin substitute fabricated using dECM-GelMA-HAMA and infused with hADSCs effectively accelerates wound healing and enhances its quality through improved angiogenesis. The stable 3D-printed stereoscopic grid-like scaffold structure, in combination with hADSCs, is paramount in the acceleration of wound healing.
Utilizing a 3D bioprinter equipped with a screw extruder, polycaprolactone (PCL) grafts were produced via screw-type and pneumatic pressure-type bioprinting methods, subsequently evaluated for comparative purposes. Single layers created with the screw-type printing method exhibited a density that was 1407% more substantial and a tensile strength that was 3476% higher than those produced by the pneumatic pressure-type method. Printed PCL grafts using the screw-type bioprinter exhibited 272 times higher adhesive force, 2989% greater tensile strength, and 6776% increased bending strength compared to PCL grafts prepared using the pneumatic pressure-type bioprinter.