bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–02–18
thirteen papers selected by
Seerat Maqsood, University of Teramo



  1. PeerJ. 2024 ;12 e16897
      Bioremediation is experiencing a paradigm shift by integrating three-dimensional (3D) bioprinting. This transformative approach augments the precision and versatility of engineering with the functional capabilities of material science to create environmental restoration strategies. This comprehensive review elucidates the foundational principles of 3D bioprinting technology for bioremediation, its current applications in bioremediation, and the prospective avenues for future research and technological evolution, emphasizing the intersection of additive manufacturing, functionalized biosystems, and environmental remediation; this review delineates how 3D bioprinting can tailor bioremediation apparatus to maximize pollutant degradation and removal. Innovations in biofabrication have yielded bio-based and biodegradable materials conducive to microbial proliferation and pollutant sequestration, thereby addressing contamination and adhering to sustainability precepts. The review presents an in-depth analysis of the application of 3D bioprinted constructs in enhancing bioremediation efforts, exemplifying the synergy between biological systems and engineered solutions. Concurrently, the review critically addresses the inherent challenges of incorporating 3D bioprinted materials into diverse ecological settings, including assessing their environmental impact, durability, and integration into large-scale bioremediation projects. Future perspectives discussed encompass the exploration of novel biocompatible materials, the automation of bioremediation, and the convergence of 3D bioprinting with cutting-edge fields such as nanotechnology and other emerging fields. This article posits 3D bioprinting as a cornerstone of next-generation bioremediation practices, offering scalable, customizable, and potentially greener solutions for reclaiming contaminated environments. Through this review, stakeholders in environmental science, engineering, and technology are provided with a critical appraisal of the current state of 3D bioprinting in bioremediation and its potential to drive forward the efficacy of environmental management practices.
    Keywords:  3D printing; Additive manufacturing; Analytical chemistry; Bioanalysis; Bioprinting; Bioremediation; Biosensing; Chemistry; Environment; Remediation
    DOI:  https://doi.org/10.7717/peerj.16897
  2. Front Pharmacol. 2024 ;15 1369505
      
    Keywords:  3D bioprinting; biosealants; clinical trial; cornea; decellularized tissues; fillers; ocular disorders; short peptide
    DOI:  https://doi.org/10.3389/fphar.2024.1369505
  3. Methods Mol Biol. 2024 ;2770 135-149
      Testes have a complex architecture that is compartmentalized into seminiferous tubules with a diameter of approximatively 200 μm in which the germ cells differentiate, surrounded by a basement membrane and interstitium. 3D bioprinting might be used to recreate the compartmentalized testicular architecture in vitro. Directed by a software program, pneumatic microextrusion printers can deposit 3D layers of hydrogel-encapsulated interstitial cells in a controlled manner by applying pressure. Once macroporous-shaped scaffolds resembling seminiferous tubules have been bioprinted with interstitial cells, the epithelial cell fraction can be seeded in the macropores to resemble the in vivo testicular architecture. Moreover, macropores can serve as a delimitation for all testicular cells to reorganize and improve the supply of nutrients to cells through the 3D constructs.
    Keywords:  3D bioprinting; Alginate; In vitro spermatogenesis; Scaffold; Spermatogonial stem cells; Testicular organoid; Tissue engineering
    DOI:  https://doi.org/10.1007/978-1-0716-3698-5_11
  4. J Biomater Sci Polym Ed. 2024 Feb 13. 1-50
      In tissue engineering and regenerative medicine applications, the utilization of bioactive materials has become a routine tool. The goal of tissue engineering is to create new organs and tissues by combining cell biology, materials science, reactor engineering, and clinical research. As part of the growth pattern for primary cells in an organ, backing material is frequently used as a supporting material. A porous three-dimensional (3D) scaffold can provide cells with optimal conditions for proliferating, migrating, differentiating, and functioning as a framework. Optimizing the scaffolds' structure and altering their surface may improve cell adhesion and proliferation. A keratin-based biomaterials platform has been developed as a result of discoveries made over the past century in the extraction, purification, and characterization of keratin proteins from hair and wool fibers. Biocompatibility, biodegradability, intrinsic biological activity, and cellular binding motifs make keratin an attractive biomaterial for tissue engineering scaffolds. Scaffolds for tissue engineering have been developed from extracted keratin proteins because of their capacity to self-assemble and polymerize into intricate 3D structures. In this review article, applications of keratin-based scaffolds in different tissues including bone, skin, nerve, and vascular are explained based on common methods of fabrication such as electrospinning, freeze-drying process, and sponge replication method.
    Keywords:  Composite; keratin; scaffold; tissue engineering
    DOI:  https://doi.org/10.1080/09205063.2024.2311450
  5. Heliyon. 2024 Feb 15. 10(3): e25400
      Articular cartilage injury is a prevalent clinical condition resulting from trauma, tumors, infection, osteoarthritis, and other factors. The intrinsic lack of blood vessels, nerves, and lymphatic vessels within cartilage tissue severely limits its self-regenerative capacity after injury. Current treatment options, such as conservative drug therapy and joint replacement, have inherent limitations. Achieving perfect regeneration and repair of articular cartilage remains an ongoing challenge in the field of regenerative medicine. Tissue engineering has emerged as a key focus in articular cartilage injury research, aiming to utilize cultured and expanded tissue cells combined with suitable scaffold materials to create viable, functional tissues. This review article encompasses the latest advancements in seed cells, scaffolds, and cytokines. Additionally, the role of stimulatory factors including cytokines and growth factors, genetic engineering techniques, biophysical stimulation, and bioreactor systems, as well as the role of scaffolding materials including natural scaffolds, synthetic scaffolds, and nanostructured scaffolds in the regeneration of cartilage tissues are discussed. Finally, we also outline the signaling pathways involved in cartilage regeneration. Our review provides valuable insights for scholars to address the complex problem of cartilage regeneration and repair.
    Keywords:  Articular cartilage injury; Cartilage regeneration; Cartilage repair; Osteoarthritis; Tissue engineering
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e25400
  6. J Nanobiotechnology. 2024 Feb 10. 22(1): 57
      Extracellular vesicles have shown promising tissue recovery-promoting effects, making them increasingly sought-after for their therapeutic potential in wound treatment. However, traditional extracellular vesicle applications suffer from limitations such as rapid degradation and short maintenance during wound administration. To address these challenges, a growing body of research highlights the role of hydrogels as effective carriers for sustained extracellular vesicle release, thereby facilitating wound healing. The combination of extracellular vesicles with hydrogels and the development of 3D bioprinting create composite hydrogel systems boasting excellent mechanical properties and biological activity, presenting a novel approach to wound healing and skin dressing. This comprehensive review explores the remarkable mechanical properties of hydrogels, specifically suited for loading extracellular vesicles. We delve into the diverse sources of extracellular vesicles and hydrogels, analyzing their integration within composite hydrogel formulations for wound treatment. Different composite methods as well as 3D bioprinting, adapted to varying conditions and construction strategies, are examined for their roles in promoting wound healing. The results highlight the potential of extracellular vesicle-laden hydrogels as advanced therapeutic tools in the field of wound treatment, offering both mechanical support and bioactive functions. By providing an in-depth examination of the various roles that these composite hydrogels can play in wound healing, this review sheds light on the promising directions for further research and development. Finally, we address the challenges associated with the application of composite hydrogels, along with emerging trends of 3D bioprinting in this domain. The discussion covers issues such as scalability, regulatory considerations, and the translation of this technology into practical clinical settings. In conclusion, this review underlines the significant contributions of hydrogel-mediated extracellular vesicle therapy to the field of 3D bioprinting and wound healing and tissue regeneration. It serves as a valuable resource for researchers and practitioners alike, fostering a deeper understanding of the potential benefits, applications, and challenges involved in utilizing composite hydrogels for wound treatment.
    Keywords:  3D bioprinting; Extracellular vesicle; Hydrogels; Regenerative medicine; Would healing
    DOI:  https://doi.org/10.1186/s12951-024-02315-9
  7. bioRxiv. 2024 Jan 30. pii: 2024.01.26.577422. [Epub ahead of print]
      Microfluidic and organ-on-a-chip devices have improved the physiologic and translational relevance of in vitro systems in applications ranging from disease modeling to drug discovery and pharmacology. However, current manufacturing approaches have limitations in terms of materials used, non-native mechanical properties, patterning of extracellular matrix (ECM) and cells in 3D, and remodeling by cells into more complex tissues. We present a method to 3D bioprint ECM and cells into microfluidic collagen-based high-resolution internally perfusable scaffolds (CHIPS) that address these limitations, expand design complexity, and simplify fabrication. Additionally, CHIPS enable size-dependent diffusion of molecules out of perfusable channels into the surrounding device to support cell migration and remodeling, formation of capillary-like networks, and integration of secretory cell types to form a glucose-responsive, insulin-secreting pancreatic-like microphysiological system.
    One-Sentence Summary: Multi-material FRESH 3D bioprinting of microfluidic CHIPS to generate fully biologic centimeter-scale and vascularized pancreatic-like tissue systems.
    DOI:  https://doi.org/10.1101/2024.01.26.577422
  8. J Biomed Mater Res B Appl Biomater. 2024 Feb;112(2): e35379
      This study emphasizes the development of a multifunctional biomaterial ink for wound healing constructs. The biomaterial ink benefits from Aloe vera's intrinsic biocompatible, biodegradable, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory attributes, thus alleviating the need for supplementary substances employed to combat infections and stimulate tissue regeneration. Moreover, this biomaterial ink seeks to address the scarcity of standardized printable materials possessing adequate biocompatibility and physicochemical properties, which hinder its widespread clinical adoption. The biomaterial ink was synthesized via ionic crosslinking to enhance its rheological and mechanical characteristics. The findings revealed that Aloe vera substantially boosted the hydrogel's viscoelastic behavior, enabling superior compressive modulus and the extrusion of fine filaments. The bioprinted constructs exhibited desirable resolution and mechanical strength while displaying a porous microstructure analogous to the native extracellular matrix. Biological response demonstrated no detrimental impact on stem cell viability upon exposure to the biomaterial ink, as confirmed by live/dead assays. These outcomes validate the potential of the developed biomaterial ink as a resource for the bioprinting of wound dressings that effectively foster cellular proliferation, thereby promoting enhanced wound healing by leveraging Aloe vera's inherent properties.
    Keywords:  Aloe vera; Extrusion-based bioprinting; Hydrogels; Skin tissue regeneration; Wound dressing
    DOI:  https://doi.org/10.1002/jbm.b.35379
  9. J Biomed Mater Res B Appl Biomater. 2024 Feb;112(2): e35364
      Millions of people have been reported with tendon injuries each year. Unfortunately, Tendon injuries are increasing rapidly due to heavy exercise and a highly aging population. In addition, the introduction of 3D-printing technology in the area of tendon repair and replacement has resolved numerous issues and significantly improved the quality of artificial tendons. This advancement has also enabled us to explore and identify the most effective combinations of biomaterials that can be utilized in this field. This review discusses the recent development of the 3D-printed artificial tendon; where recently, some research investigated the most suitable pore sizes, diameter, and strength for scaffolds to have high tendon cells ingrowth and proliferation, giving a better understanding of the effects of densities and structure patterns on tendon's mechanical properties. In addition, it presents the divergence between 3D-printed tendons and other tissue and how the different 3D-printing techniques and models participated in this development.
    Keywords:  3D-artificial tendon; 3D-printing techniques; biological materials; extrusion bio-printing; tendon scaffolds
    DOI:  https://doi.org/10.1002/jbm.b.35364
  10. Adv Healthc Mater. 2024 Feb 16. e2303217
      Osteochondral defects are often accompanied by excessive reactive oxygen species (ROS) caused by osteoarthritis or acute surgical inflammation. An inflammatory environment containing excess ROS will not only hinder tissue regeneration, but also impact the quality of newly formed tissues. Therefore, there is an urgent need to develop scaffolds with both ROS scavenging and osteochondral repair functions to promote and protect osteochondral tissue regeneration. In this work, by using 3D printing technology, we developed a composite scaffold based on cobalt-incorporated chloroapatite (Co-ClAP) bioceramics, which possessed ROS-scavenging activity and could support cell proliferation, adhesion, and differentiation. Benefiting from the catalytic activity of Co-ClAP bioceramics, the composite scaffold could protect cells from oxidative damage under ROS-excessive conditions, support their directional differentiation, and simultaneously mediate an anti-inflammatory microenvironment. In addition, it was also confirmed by using rabbit osteochondral defect model that the cobalt-incorporated chloroapatite/Poly (lactic-co-glycolic acid) (Co-ClAP/PLGA) scaffold could effectively promote the integrated regeneration of cartilage and subchondral bone, exhibiting an ideal repair effect in vivo. This study provides a promising strategy for the treatment of defects with excess ROS and inflammatory microenvironments. This article is protected by copyright. All rights reserved.
    Keywords:  3D printing; bioceramic scaffolds; osteochondral regeneration; reactive oxygen species
    DOI:  https://doi.org/10.1002/adhm.202303217
  11. J Nanobiotechnology. 2024 Feb 12. 22(1): 59
       BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities.
    RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-β (TGF-β) signaling pathway.
    CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.
    Keywords:  3D printed; Bone regeneration; Macrophages; Osteoimmune microenvironment remodeling; Xonotlite nanofiber
    DOI:  https://doi.org/10.1186/s12951-024-02323-9
  12. Int J Biol Macromol. 2024 Feb 08. pii: S0141-8130(24)00878-X. [Epub ahead of print]262(Pt 1): 130075
      Skin tissue engineering faces challenges due to the absence of vascular architecture, impeding the development of permanent skin replacements. To address this, a heparin-functionalized 3D-printed bioink (GH/HepMA) was formulated to enable sustained delivery of vascular endothelial growth factor (VEGF), comprising 0.3 % (w/v) hyaluronic acid (HA), 10 % (w/v) gelatin methacrylate (GelMA), and 0.5 % (w/v) heparin methacrylate (HepMA). The bioink was then used to print dermal constructs with angiogenic functions, including fibroblast networks and human umbilical vein endothelial cell (HUVEC) networks. GH/HepMA, with its covalently cross-linked structure, exhibits enhanced mechanical properties and heparin stability, allowing for a 21-day sustained delivery of VEGF. Cytocompatibility experiments showed that the GH/HepMA bioink supported fibroblast proliferation and promoted collagen I production. With VEGF present, the GH/HepMA bioink promoted HUVEC proliferation, migration, as well as the formation of a richer capillary-like network. Furthermore, HA within the GH/HepMA bioink enhanced rheological properties and printability. Additionally, 3D-bioprinted dermal constructs showed significant deposition of collagen I and III and mature stable capillary-like structures along the axial direction. In summary, this study offers a promising approach for constructing biomimetic multicellular skin substitutes with angiogenesis-induced functions.
    Keywords:  3D-printed; Angiogenesis; Methacrylated heparin
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.130075