bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023‒07‒23
twelve papers selected by
Seerat Maqsood
University of Teramo

  1. Int J Bioprint. 2023 ;9(5): 759
      Three-dimensional (3D) bioprinting is a promising and innovative biomanufacturing technology, which can achieve precise position controlling of cells and extracellular matrix components, and further create complex and functional multi-cellular tissues or organs in a 3D environment. Bioink in the form of the cell-loaded hydrogel is most commonly used in bioprinting, and it is vital to the process of bioprinting. The bionic scaffold should possess suitable mechanical strength, biocompatibility, cell proliferation, survival, and other biological characteristics. The disadvantages of natural polymer hydrogel materials include poor mechanical properties as well as low printing performance and shape fidelity. Over the past years, a series of synthetic, modified, and nanocomposite hydrogels have been developed, which can interact through physical interactions, chemical covalent bond crosslinking, and bioconjugation reactions to change the characteristics to satisfy the requirements. In this review, a comprehensive summary is provided on recent research regarding the unique properties of hydrogel bioinks for bioprinting, with optimized methods and technologies highlighted, which have both high-value research significance and potential clinical applications. A critical analysis of the strengths and weaknesses of each hydrogel-based biomaterial ink is presented at the beginning or end of each section, alongside the latest improvement strategies employed by current researchers to address their respective shortcomings. Furthermore, we propose potential repair sites for each hydrogel-based ink based on their distinctive repair features, while reflecting on current research limitations. Finally, we synthesize and analyze expert opinions on the future of these hydrogel-based bioinks in the broader context of tissue engineering and regenerative medicine, offering valuable insights for future investigations.
    Keywords:  3D bioprinting; Bioink; Bionic scaffold; Hydrogel; Tissue engineering
  2. Int J Bioprint. 2023 ;9(5): 753
      Three-dimensional (3D) bioprinting technology is one of the most advanced techniques currently applied in tissue engineering and regenerative medicine and has developed rapidly in the past few years. Despite many breakthroughs, there are still several challenges of 3D bioprinting technology awaiting to be addressed, and one of them is the urgency of optimizing bioinks (natural or synthetic hydrogel), which are critical elements in 3D bioprinting, for specific properties. Different from traditional hydrogels, microgels, which are a new type of bioink, are micron-sized gels with excellent mechanical and biological properties, which make them great candidates for applications in 3D bioprinting. Different from the dense and limited pore size of traditional hydrogels, the pore structure of microgel is adjustable, enabling better cell loading before 3D bioprinting, and the printed pores are conducive to the exchange of metabolic substances and cell migration. The "bottom-up" modular microgel has stronger customizable characteristics, and it can freely adjust its mechanical properties, such as hardness, toughness, and rheological properties. In this review, we review the application of microgels in the field of biomedicine and discuss the future development of microgels in 3D bioprinting.
    Keywords:  3D bioprinting; Bioink; Microgel; Tissue engineering
  3. Int J Bioprint. 2023 ;9(5): 757
      The skin plays an important role in vitamin D synthesis, humoral balance, temperature regulation, and waste excretion. Due to the complexity of the skin, fluids loss, bacterial infection, and other life-threatening secondary complications caused by skin defects often lead to the damage of skin functions. 3D bioprinting technology, as a customized and precise biomanufacturing platform, can manufacture dressings and tissue engineering scaffolds that accurately simulate tissue structure, which is more conducive to wound healing. In recent years, with the development of emerging technologies, an increasing number of 3D-bioprinted wound dressings and skin tissue engineering scaffolds with multiple functions, such as antibacterial, antiinflammatory, antioxidant, hemostatic, and antitumor properties, have significantly improved wound healing and skin treatment. In this article, we review the process of wound healing and summarize the classification of 3D bioprinting technology. Following this, we shift our focus on the functional materials for wound dressing and skin tissue engineering, and also highlight the research progress and development direction of 3D-bioprinted multifunctional wound healing materials.
    Keywords:  3D bioprinting; Dressing; Functional materials; Skin tissue engineering; Wound healing
  4. J Tissue Eng. 2023 Jan-Dec;14:14 20417314231187113
      Three-dimensional (3D) bioprinting is a promising and rapidly evolving technology in the field of additive manufacturing. It enables the fabrication of living cellular constructs with complex architectures that are suitable for various biomedical applications, such as tissue engineering, disease modeling, drug screening, and precision regenerative medicine. The ultimate goal of bioprinting is to produce stable, anatomically-shaped, human-scale functional organs or tissue substitutes that can be implanted. Although various bioprinting techniques have emerged to develop customized tissue-engineering substitutes over the past decade, several challenges remain in fabricating volumetric tissue constructs with complex shapes and sizes and translating the printed products into clinical practice. Thus, it is crucial to develop a successful strategy for translating research outputs into clinical practice to address the current organ and tissue crises and improve patients' quality of life. This review article discusses the challenges of the existing bioprinting processes in preparing clinically relevant tissue substitutes. It further reviews various strategies and technical feasibility to overcome the challenges that limit the fabrication of volumetric biological constructs and their translational implications. Additionally, the article highlights exciting technological advances in the 3D bioprinting of anatomically shaped tissue substitutes and suggests future research and development directions. This review aims to provide readers with insight into the state-of-the-art 3D bioprinting techniques as powerful tools in engineering functional tissues and organs.
    Keywords:  3D bioprinting; clinical translation; organ engineering; tissue analogs; volumetric biological structures
  5. J Vis Exp. 2023 06 30.
      Phototunable hydrogels can transform spatially and temporally in response to light exposure. Incorporating these types of biomaterials in cell-culture platforms and dynamically triggering changes, such as increasing microenvironmental stiffness, enables researchers to model changes in the extracellular matrix (ECM) that occur during fibrotic disease progression. Herein, a method is presented for 3D bioprinting a phototunable hydrogel biomaterial capable of two sequential polymerization reactions within a gelatin support bath. The technique of Freeform Reversible Embedding of Suspended Hydrogels (FRESH) bioprinting was adapted by adjusting the pH of the support bath to facilitate a Michael addition reaction. First, the bioink containing poly(ethylene glycol)-alpha methacrylate (PEGαMA) was reacted off-stoichiometry with a cell-degradable crosslinker to form soft hydrogels. These soft hydrogels were later exposed to photoinitator and light to induce the homopolymerization of unreacted groups and stiffen the hydrogel. This protocol covers hydrogel synthesis, 3D bioprinting, photostiffening, and endpoint characterizations to assess fibroblast activation within 3D structures. The method presented here enables researchers to 3D bioprint a variety of materials that undergo pH-catalyzed polymerization reactions and could be implemented to engineer various models of tissue homeostasis, disease, and repair.
  6. Adv Healthc Mater. 2023 Jul 20. e2301338
      Cardiovascular disease is a major cause of mortality worldwide, and current preclinical models including traditional animal models and 2D cell culture models have limitations in replicating human native heart physiology and response to drugs. Heart-on-a-chip (HoC) technology offers a promising solution by combining the advantages of cardiac tissue engineering and microfluidics to create in vitro 3D cardiac models, which can mimic key aspects of human microphysiological systems and provide controllable microenvironments. In this review, we introduce recent advances in HoC technologies, including engineered cardiac microtissue construction in vitro, microfluidic chip fabrication, microenvironmental stimulation, and real-time feedback systems. We focus on the development of cardiac tissue engineering methods for 3D microtissue preparation, advanced strategies for HoC fabrication, and current applications of these platforms. We also discuss major challenges in HoC fabrication and provide our perspective on the potential for these platforms to advance research and clinical applications. This article is protected by copyright. All rights reserved.
    Keywords:  cardiac tissue engineering; heart-on-a-chip; microenvironment control; microfluidics
  7. Int J Bioprint. 2023 ;9(5): 761
      Temporomandibular joint (TMJ) osteoarthritis causes fibrocartilage damage to the TMJ disc and mandibular condyle, resulting in local pain and functional impairment that further reduces patients' quality of life. Tissue engineering offers a potential treatment for fibrocartilage regeneration of the TMJ disc and mandibular condyle. However, the heterogeneous structure of TMJ fibrocartilage tissue poses significant challenges for the fabrication of biomimetic scaffolds. Over the past two decades, some researchers have attempted to adopt three-dimensional (3D) printing techniques to fabricate biomimetic scaffolds for TMJ fibrocartilage regeneration, but publications on such attempts are limited and rarely report satisfactory results, indicating an urgent need for further development. This review outlines several popular 3D printing techniques and the significant elements of tissue-engineered scaffolds: seed cells, scaffold materials, and bioactive factors. Current research progress on 3D-printed scaffolds for fibrocartilage regeneration of the TMJ disc and mandibular condyle is reviewed. The current challenges in TMJ tissue engineering are mentioned along with some emerging tissue-engineering strategies, such as machine learning, stimuli-responsive delivery systems, and extracellular vesicles, which are considered as potential approaches to improve the performance of 3D-printed scaffolds for TMJ fibrocartilage regeneration. This review is expected to inspire the further development of 3D printing techniques for TMJ fibrocartilage regeneration.
    Keywords:  3D printing; Cartilage regeneration; Mandibular condyle; Temporomandibular joint disc
  8. Int J Bioprint. 2023 ;9(5): 762
      This article provides an overview of the different types of blood-derived biomaterials that can be used as solvent additives in the formulation of inks/bioinks for use in solvent extrusion printing/bioprinting. We discuss the properties of various blood sub-products obtained after blood fractionation in terms of their use in tailoring ink/bioink to produce functional constructs designed to improve tissue repair. Blood-derived additives include platelets and/or their secretome, including signaling proteins and microvesicles, which can drive cell migration, inflammation, angiogenesis, and synthesis of extracellular matrix proteins. The contribution of plasma to ink/bioink functionalization relies not only on growth factors, such as hepatocyte growth factor and insulin growth factors, but also on adhesive proteins, such as fibrinogen/fibrin, vitronectin, and fibronectin. We review the current developments and progress in solvent-based extrusion printing/bioprinting with inks/bioinks functionalized with different blood-derived products, leading toward the development of more advanced patient-specific 3D constructs in multiple medical fields, including but not limited to oral tissues and cartilage, bone, skin, liver, and neural tissues. This information will assist researchers in identifying the most suitable blood-derived product for their ink/bioink formulation based on the intended regenerative functionality of the target tissue.
    Keywords:  3D printing; Bioprinting; Blood-derived products; Functionalized bioinks; Plasma; Solvent-based extrusion; Tissue grafts/implants
  9. Bioeng Transl Med. 2023 Jul;8(4): e10503
      3D printing is a state-of-the-art technology for the fabrication of biomaterials with myriad applications in translational medicine. After stimuli-responsive properties were introduced to 3D printing (known as 4D printing), intelligent biomaterials with shape configuration time-dependent character have been developed. Polysaccharides are biodegradable polymers sensitive to several physical, chemical, and biological stimuli, suited for 3D and 4D printing. On the other hand, engineering of mechanical strength and printability of polysaccharide-based scaffolds along with their aneural, avascular, and poor metabolic characteristics need to be optimized varying printing parameters. Multiple disciplines such as biomedicine, chemistry, materials, and computer sciences should be integrated to achieve multipurpose printable biomaterials. In this work, 3D and 4D printing technologies are briefly compared, summarizing the literature on biomaterials engineering though printing techniques, and highlighting different challenges associated with 3D/4D printing, as well as the role of polysaccharides in the technological shift from 3D to 4D printing for translational medicine.
    Keywords:  3D printing; 4D printing; bioprinting; carbohydrate polymers; polysaccharides; translational medicine
  10. Front Bioeng Biotechnol. 2023 ;11 1168504
      Population ageing and various diseases have increased the demand for bone grafts in recent decades. Bone tissue engineering (BTE) using a three-dimensional (3D) scaffold helps to create a suitable microenvironment for cell proliferation and regeneration of damaged tissues or organs. The 3D printing technique is a beneficial tool in BTE scaffold fabrication with appropriate features such as spatial control of microarchitecture and scaffold composition, high efficiency, and high precision. Various biomaterials could be used in BTE applications. PCL, as a thermoplastic and linear aliphatic polyester, is one of the most widely used polymers in bone scaffold fabrication. High biocompatibility, low cost, easy processing, non-carcinogenicity, low immunogenicity, and a slow degradation rate make this semi-crystalline polymer suitable for use in load-bearing bones. Combining PCL with other biomaterials, drugs, growth factors, and cells has improved its properties and helped heal bone lesions. The integration of PCL composites with the new 3D printing method has made it a promising approach for the effective treatment of bone injuries. The purpose of this review is give a comprehensive overview of the role of printed PCL composite scaffolds in bone repair and the path ahead to enter the clinic. This study will investigate the types of 3D printing methods for making PCL composites and the optimal compounds for making PCL composites to accelerate bone healing.
    Keywords:  3D printed PCL; 3D printing; PCL composites; bone scaffolds; bone tissue engineering
  11. ACS Biomater Sci Eng. 2023 Jul 18.
      Cryogel-based scaffolds have attracted great attention in tissue engineering due to their interconnected macroporous structures. However, three-dimensional (3D) printing of cryogels with a high degree of precision and complexity is a challenge, since the synthesis of cryogels occurs under cryogenic conditions. In this study, we demonstrated the fabrication of cryogel-based scaffolds for the first time by using an embedded printing technique. A photo-cross-linkable gelatin methacryloyl (GelMA)-based ink composition, including alginate and photoinitiator, was printed into a nanoclay-based support bath. The layer-by-layer extruded ink was held in complex and overhanging structures with the help of pre-cross-linking of alginate with Ca2+ present in the support bath. The printed 3D structures in the support bath were frozen, and then GelMA was cross-linked at a subzero temperature under UV light. The printed and cross-linked structures were successfully recovered from the support bath with an integrated shape complexity. SEM images showed the formation of a 3D printed scaffold where porous GelMA cryogel was integrated between the cross-linked alginate hydrogels. In addition, they showed excellent shape recovery under uniaxial compression cycles of up to 80% strain. In vitro studies showed that the human fibroblast cells attached to the 3D printed scaffold and displayed spread morphology with a high proliferation rate. The results revealed that the embedded 3D printing technique enables the fabrication of cytocompatible cryogel based scaffolds with desired morphology and mechanical behavior using photo-cross-linkable bioink composition. The properties of the cryogels can be modified by varying the GelMA concentration, whereby various shapes of scaffolds can be fabricated to meet the specific requirements of tissue engineering applications.
    Keywords:  GelMA; alginate; cryogel; embedded 3D printing; scaffold; self-recovery
  12. Acta Biomater. 2023 Jul 14. pii: S1742-7061(23)00399-9. [Epub ahead of print]
      3D-printed composite scaffolds have emerged as an alternative to deal with existing limitations when facing bone reconstruction. The aim of the study was to systematically review the feasibility of using PLA/bioceramic composite scaffolds manufactured by 3D-printing technologies as bone grafting materials in preclinical in vivo studies. Electronic databases were searched using specific search terms, and thirteen manuscripts were selected after screening. The synthesis of the scaffolds was carried out using mainly extrusion-based techniques. Likewise, hydroxyapatite was the most used bioceramic for synthesizing composites with a PLA matrix. Among the selected studies, seven were conducted in rats and six in rabbits, but the high variability that exists regarding the experimental process made it difficult to compare them. Regarding the results, PLA/Bioceramic composite scaffolds have shown to be biocompatible and mechanically resistant. Preclinical studies elucidated the ability of the scaffolds to be used as bone grafts, allowing bone growing without adverse reactions. In conclusion, PLA/Bioceramics scaffolds have been demonstrated to be a promising alternative for treating bone defects. Nevertheless, more care should be taken when designing and performing in vivo trials, since the lack of standardization of the processes, which prevents the comparison of the results and reduces the quality of the information. STATEMENT OF SIGNIFICANCE: 3D-printed polylactic acid/bioceramic composite scaffolds have emerged as an alternative to deal with existing limitations when facing bone reconstruction. Since preclinical in vivo studies with animal models represent a mandatory step for clinical translation, the present manuscript analyzed and discussed not only those aspects related to the selection of the bioceramic material, the synthesis of the implants and their characterization. But provides a new approach to understand how the design and perform of clinical trials, as well as the selection of the analysis methods, may affect the obtained results, by covering authors' knowledgebase from veterinary medicine to biomaterial science. Thus, this study aims to systematically review the feasibility of using polylactic acid/bioceramic scaffolds as grafting materials in preclinical trials.
    Keywords:  3D-printing technology; Animal models; bioceramic; bone regeneration; composite scaffolds; polylactic acid