bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023‒11‒12
twelve papers selected by
Seerat Maqsood, University of Teramo

  1. Biofabrication. 2023 Nov 09.
      Three-dimensional (3D) bioprinting offers promising solutions to the complex challenge of vascularization in biofabrication, thereby enhancing the prospects for clinical translation of engineered tissues and organs. While existing reviews have touched upon 3D bioprinting in vascularized tissue contexts, the current review offers a more holistic perspective, encompassing recent technical advancements and spanning the entire multistage bioprinting process, with a particular emphasis on vascularization. The synergy between 3D bioprinting and vascularization strategies is crucial, as 3D bioprinting can enable the creation of personalized, tissue-specific vascular network while the vascularization enhances tissue viability and function. The review starts by providing a comprehensive overview of the entire bioprinting process, spanning from pre-bioprinting stages to post-printing processing, including perfusion and maturation. Next, recent advancements in vascularization strategies that can be seamlessly integrated with bioprinting are discussed. Further, tissue-specific examples illustrating how these vascularization approaches are customized for diverse anatomical tissues towards enhancing clinical relevance are discussed. Finally, the underexplored intraoperative bioprinting was highlighted, which enables the direct reconstruction of tissues within defect sites, stressing on the possible synergy shaped by combining intraoperative bioprinting with vascularization strategies for improved regeneration.
    Keywords:  Bioprinting; Intraoperative bioprinting; Tissue and organ substitutes; Vascularization; Vascularized tissues
  2. Heart Fail Rev. 2023 Nov 09.
      Cardiovascular diseases (CVDs) represent a paramount global mortality concern, and their prevalence is on a relentless ascent. Despite the effectiveness of contemporary medical interventions in mitigating CVD-related fatality rates and complications, their efficacy remains curtailed by an array of limitations. These include the suboptimal efficiency of direct cell injection and an inherent disequilibrium between the demand and availability of heart transplantations. Consequently, the imperative to formulate innovative strategies for cardiac regeneration therapy becomes unmistakable. Within this context, 3D bioprinting technology emerges as a vanguard contender, occupying a pivotal niche in the realm of tissue engineering and regenerative medicine. This state-of-the-art methodology holds the potential to fabricate intricate heart tissues endowed with multifaceted structures and functionalities, thereby engendering substantial promise. By harnessing the prowess of 3D bioprinting, it becomes plausible to synthesize functional cardiac architectures seamlessly enmeshed with the host tissue, affording a viable avenue for the restitution of infarcted domains and, by extension, mitigating the onerous yoke of CVDs. In this review, we encapsulate the myriad applications of 3D bioprinting technology in the domain of heart tissue regeneration. Furthermore, we usher in the latest advancements in printing methodologies and bioinks, culminating in an exploration of the extant challenges and the vista of possibilities inherent to a diverse array of approaches.
    Keywords:  3D bioprinting; Cardiac tissue engineering; Myocardial patch; Regeneration; Stem cells
  3. Drug Discov Today. 2023 Nov 08. pii: S1359-6446(23)00339-2. [Epub ahead of print] 103823
      Three-dimensional (3D) printing is a promising approach for the stabilization and delivery of non-living biologics. This versatile tool builds complex structures and customized resolutions, and has significant potential in various industries, especially pharmaceutics. Biologics have become increasingly prevalent in the field of medicine due to their diverse applications and benefits. Stability is the main attribute that must be achieved during the development of biologic formulations. 3D printing could help to stabilize biologics by entrapment, support binding, or crosslinking. Furthermore, gene fragments could be transited into cells during co-printing, when the pores on the membrane are enlarged. This review provides: (i) an introduction to 3D printing technologies and biologics, covering genetic elements, therapeutic proteins, antibodies, and bacteriophages; (ii) an overview of the applications of 3D printing of biologics, including regenerative medicine, gene therapy, and personalized treatments; (iii) information on how 3D printing could help to stabilize and deliver biologics; and (iv) discussion on regulations, challenges, and future directions, including microneedle vaccines, novel 3D printing technologies and artificial-intelligence-facilitated research and product development. Overall, the 3D printing of biologics holds great promise for enhancing human health by providing extended longevity and enhanced quality of life, making it an exciting area in the rapidly evolving field of biomedicine.
    Keywords:  3D bioprinting; 3D printing biologics; microneedles; protein delivery; vaccine
  4. Front Cell Dev Biol. 2023 ;11 1258993
      We have previously shown that human and murine breast extracellular matrix (ECM) can significantly impact cellular behavior, including stem cell fate determination. It has been established that tissue-specific extracellular matrix from the central nervous system has the capacity to support neuronal survival. However, the characterization of its influence on stem cell differentiation and its adaptation to robust 3D culture models is underdeveloped. To address these issues, we combined our 3D bioprinter with hydrogels containing porcine brain extracellular matrix (BMX) to test the influence of the extracellular matrix on stem cell differentiation. Our 3D bioprinting system generated reproducible 3D neural structures derived from mouse embryonic stem cells (mESCs). We demonstrate that the addition of BMX preferentially influences 3D bioprinted mESCs towards neural lineages compared to standard basement membrane (Geltrex/Matrigel) hydrogels alone. Furthermore, we demonstrate that we can transplant these 3D bioprinted neural cellular structures into a mouse's cleared mammary fat pad, where they continue to grow into larger neural outgrowths. Finally, we demonstrate that direct injection of human induced pluripotent stem cells (hiPSCS) and neural stem cells (NSCs) suspended in pure BMX formed neural structures in vivo. Combined, these findings describe a unique system for studying brain ECM/stem cell interactions and demonstrate that BMX can direct pluripotent stem cells to differentiate down a neural cellular lineage without any additional specific differentiation stimuli.
    Keywords:  3D bioprinting; brain; cellular microenvironment; extracellular matrix; fate determination; neural differentiation; stem cells
  5. Mater Today Bio. 2023 Dec;23 100826
      The use of three-dimensional (3D) bioprinting has been proposed for the reproducible production of 3D disease models that can be used for high-throughput drug testing and personalized medicine. However, most such models insufficiently reproduce the features and environment of real tumors. We report the development of bioprinted in vitro 3D tumor models for breast cancer, which physically and biochemically mimic important aspects of the native tumor microenvironment, designed to study therapeutic efficacy. By combining a mix of breast decellularized extracellular matrix and methacrylated hyaluronic acid with tumor-derived cells and non-cancerous stromal cells of biological relevance to breast cancer, we show that biological signaling pathways involved in tumor progression can be replicated in a carefully designed tumor-stroma environment. Finally, we demonstrate proof-of-concept application of these models as a reproducible platform for investigating therapeutic responses to commonly used chemotherapeutic agents.
    Keywords:  3D bioprinting; 3D tumor models; Bioinks; Breast cancer; Drug testing; Tumor microenvironment; dECM
  6. Clin Oral Implants Res. 2023 Nov 06.
      OBJECTIVES: This scoping review aimed to identify the available evidence in the use of 3D printing technology in dental implantology. Due to the broad scope of the subject and its application in implantology, three main areas of focus were identified: (1) customized dental implants, (2) manufacturing workflow for surgical implant guides, and (3) related implant-supported prostheses factors, which include the metallic primary frameworks, secondary ceramic or polymer superstructures, and 3D implant analog models.MATERIALS AND METHODS: Online databases (Medline, Cochrane, Embase, and CINAHL) were used to identify the studies published up to February 2023 in English. Two experienced reviewers performed independently the screening and selection among the 1737 studies identified. The articles evaluated the additive manufacturing (AM) technology, materials, printing, and post-processing parameters regarding dental implantology.
    RESULTS: The 132 full-text studies that met the inclusion criteria were examined. Thirteen studies of customized dental implants, 22 studies about the workflow for surgical implant guides, and 30 studies of related implant-supported prostheses factors were included.
    CONCLUSIONS: (1) The clinical evidence about AM titanium and zirconia implants is scarce. Early data on survival rates, osseointegration, and mechanical properties are being reported. (2) 3D printing is a proven manufacturing technology to produce surgical implant guides. Adherence to the manufacturer's instructions is crucial and the best accuracy was achieved using MultiJet printer. (3) The quality of 3D printed prosthetic structures and superstructures is improving remarkably, especially on metallic alloys. However, better marginal fit and mechanical properties can be achieved with milling technology for metals and ceramics.
    Keywords:  3D printing; additive manufacturing; implantology; prosthodontics; scoping review
  7. Bladder (San Franc). 2023 ;10 e21200005
      Bladder cancer represents the most common malignancy of the urinary system, posing a significant threat to patients' life. Animal models and two-dimensional (2D) cell cultures, among other traditional models, have been used for years to study various aspects of bladder cancer. However, these methods are subject to various limitations when mimicking the tumor microenvironment in vivo, thus hindering the further improvement of bladder cancer treatments. Recently, three-dimensional (3D) culture models have attracted extensive attention since they overcome the shortcomings of their traditional counterparts. Most importantly, 3D culture models more accurately reproduce the tumor microenvironment in the human body because they can recapitulate the cell-cell and cell-extracellular matrix interactions. 3D culture models can thereby help us gain deeper insight into the bladder cancer. The 3D culture models of tumor cells can extend the culture duration and allow for co-culturing with different cell types. Study of patient-specific bladder cancer mutations and subtypes is made possible by the ability to preserve cells isolated from particular patients in 3D culture models. It will be feasible to develop customized treatments that target relevant signaling pathways or biomarkers. This article reviews the development, application, advantages, and limitations of traditional modeling systems and 3D culture models used in the study of bladder cancer and discusses the potential application of 3D culture models.
    Keywords:  3D bioprinting; 3D culture models; bladder cancer; cell culture
  8. Adv Healthc Mater. 2023 Nov 05. e2302879
      Bone infection is one of the most devastating orthopedic outcomes, and overuse of antibiotics maybe cause drug-resistance problems. Photothermal therapy is a promising antibiotic-free strategy for treating infected bone defects. Considering the damage to normal tissues and cells caused by high-temperature conditions in photothermal therapy, this study combines the antibacterial property of Cu to construct a multi-functional Cu2 O@MXene/alpha-tricalcium phosphate scaffold support with internal and external sandwiching through 3D printing technology. On the "outside", the excellent photothermal property of Ti3 C2 MXene is used to carry out the programmed temperature control by the active regulation of 808 nm near-infrared light. On the "inside", endogenous Cu ions gradually release and the release accumulates within the safe dose range. Specifically, programmed temperature control includes brief photothermal therapy to rapidly kill early bacteria and periodic low photothermal stimulation to promote bone tissue growth, which reduces damage to healthy cells and tissues. Meanwhile, Cu ions are gradually released from the scaffold over a long period of time, strengthening the antibacterial effect of early photothermal therapy, and promoting angiogenesis to improve the repair effect. Photothermal therapy combined with Cu can deliver a new idea for long-term prevention of infected bone defects through in vitro and vivo application. This article is protected by copyright. All rights reserved.
    Keywords:  antibacterial; bone infection; photothermal therapy
  9. Adv Mater. 2023 Nov 07. e2310100
      Since the pioneering work of Kawata and colleagues in 1997, multi-photon 3D laser printing, also known as direct laser writing (DLW), has made significant advancements in a wide range of fields. Moreover, the development and commercialization of photocurable inks for this technique have expanded rapidly. One of the current trends is the transition from static to active printable materials, often referred to as 4D microprinting, which enables a new degree of control in the printed systems. This review focuses on four primary application areas: microrobotics, optics and photonics, microfluidics, and life sciences, highlighting recent progress and the crucial role of active materials, including liquid crystalline elastomers, hydrogels, shape memory polymers and composites, among others. It also addresses ongoing challenges and provides insights into the future prospects in the different fields. This article is protected by copyright. All rights reserved.
    Keywords:  4D printing; direct laser writing; microrobotics; smart polymers; two-photon polymerization
  10. J Vis Exp. 2023 Oct 20.
      Due to the complex structure and important functions of the skin, it is an interesting research model for the cosmetic, pharmaceutical, and medical industries. In the European Union, there has been a total ban on testing cosmetic products and their ingredients on animals. In the case of medicine and pharmaceuticals, this possibility is also constantly limited. In accordance with the 3Rs principle, it is becoming more and more common to test individual compounds as well as entire formulations on artificially created models. The cheapest and most widely used are the 2D models, which consist of a cell monolayer but do not reflect the real interactions between the cells in the tissue. Although the commercially available 3D models provide a better representation of the tissue, they are not used on a large scale. This is because they are expensive, the waiting time is quite long, and the available models are frequently limited to only those typically used. In order to move the conducted research to a higher level, we have optimized the procedures of various 3D skin model preparations. The described procedures are cheap and simple to prepare as they can be applied in numerous laboratories and by researchers with different experiences in cell culture.
  11. Biofabrication. 2023 Nov 10. 16(1):
      Methods for studying brain function and disease heavily rely onin vivoanimal models,ex-vivotissue slices, and 2D cell culture platforms. These methods all have limitations that significantly impact the clinical translatability of results. Consequently, models able to better recapitulate some aspects ofin vivohuman brain are needed as additional preclinical tools. In this context, 3D hydrogel-basedin vitromodels of the brain are considered promising tools. To create a 3D brain-on-a-chip model, a hydrogel capable of sustaining neuronal maturation over extended culture periods is required. Among biopolymeric hydrogels, chitosan-β-glycerophosphate (CHITO-β-GP) thermogels have demonstrated their versatility and applicability in the biomedical field over the years. In this study, we investigated the ability of this thermogel to encapsulate neuronal cells and support the functional maturation of a 3D neuronal network in long-term cultures. To the best of our knowledge, we demonstrated for the first time that CHITO-β-GP thermogel possesses optimal characteristics for promoting neuronal growth and the development of an electrophysiologically functional neuronal network derived from both primary rat neurons and neurons differentiated from human induced pluripotent stem cells (h-iPSCs) co-cultured with astrocytes. Specifically, two different formulations were firstly characterized by rheological, mechanical and injectability tests. Primary nervous cells and neurons differentiated from h-iPSCs were embedded into the two thermogel formulations. The 3D cultures were then deeply characterized by immunocytochemistry, confocal microscopy, and electrophysiological recordings, employing both 2D and 3D micro-electrode arrays. The thermogels supported the long-term culture of neuronal networks for up to 100 d. In conclusion, CHITO-β-GP thermogels exhibit excellent mechanical properties, stability over time under culture conditions, and bioactivity toward nervous cells. Therefore, they are excellent candidates as artificial extracellular matrices in brain-on-a-chip models, with applications in neurodegenerative disease modeling, drug screening, and neurotoxicity evaluation.
    Keywords:  3D neuronal cultures; brain-on-a-chip; chitosan-β-glycerophosphate thermogel; injectability; soft hydrogels
  12. Small. 2023 Nov 10. e2307178
      This work reports the rational design and fabrication of magneto-active microfiber meshes with controlled hexagonal microstructures via melt electrowriting (MEW) of a magnetized polycaprolactone-based composite. In situ iron oxide nanoparticle deposition on oxidized graphene yields homogeneously dispersed magnetic particles with sizes above 0.5 µm and low aspect ratio, preventing cellular internalization and toxicity. With these fillers, homogeneous magnetic composites with high magnetic content (up to 20 weight %) are obtained and processed in a solvent-free manner for the first time. MEW of magnetic composites enabled the creation of skeletal muscle-inspired design of hexagonal scaffolds with tunable fiber diameter, reconfigurable modularity, and zonal distribution of magneto-active and nonactive material, with elastic tensile deformability. External magnetic fields below 300 mT are sufficient to trigger out-of-plane reversible deformation. In vitro culture of C2C12 myoblasts on three-dimensional (3D) Matrigel/collagen/MEW scaffolds showed that microfibers guided the formation of 3D myotube architectures, and the presence of magnetic particles does not significantly affect viability or differentiation rates after 8 days. Centimeter-sized skeletal muscle constructs allowed for reversible, continued, and dynamic magneto-mechanical stimulation. Overall, these innovative microfiber scaffolds provide magnetically deformable platforms suitable for dynamic culture of skeletal muscle, offering potential for in vitro disease modeling.
    Keywords:  fiber scaffolds; magnetic actuation; melt electrowriting; skeletal muscle; stimuli responsive biomaterials