bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023–07–16
nine papers selected by
Seerat Maqsood, University of Teramo



  1. Bioact Mater. 2023 Oct;28 511-536
      Bioinks are formulations of biomaterials and living cells, sometimes with growth factors or other biomolecules, while extrusion bioprinting is an emerging technique to apply or deposit these bioinks or biomaterial solutions to create three-dimensional (3D) constructs with architectures and mechanical/biological properties that mimic those of native human tissue or organs. Printed constructs have found wide applications in tissue engineering for repairing or treating tissue/organ injuries, as well as in vitro tissue modelling for testing or validating newly developed therapeutics and vaccines prior to their use in humans. Successful printing of constructs and their subsequent applications rely on the properties of the formulated bioinks, including the rheological, mechanical, and biological properties, as well as the printing process. This article critically reviews the latest developments in bioinks and biomaterial solutions for extrusion bioprinting, focusing on bioink synthesis and characterization, as well as the influence of bioink properties on the printing process. Key issues and challenges are also discussed along with recommendations for future research.
    Keywords:  3D bioprinting; Bioinks; Biomaterials; Extrusion; Tissue engineering
    DOI:  https://doi.org/10.1016/j.bioactmat.2023.06.006
  2. Crit Rev Biotechnol. 2023 Jul 13. 1-32
      3D bioprinting is an advanced technology combining cells and bioactive molecules within a single bioscaffold; however, this scaffold cannot change, modify or grow in response to a dynamic implemented environment. Lately, a new era of smart polymers and hydrogels has emerged, which can add another dimension, e.g., time to 3D bioprinting, to address some of the current approaches' limitations. This concept is indicated as 4D bioprinting. This approach may assist in fabricating tissue-like structures with a configuration and function that mimic the natural tissue. These scaffolds can change and reform as the tissue are transformed with the potential of specific drug or biomolecules released for various biomedical applications, such as biosensing, wound healing, soft robotics, drug delivery, and tissue engineering, though 4D bioprinting is still in its early stages and more works are required to advance it. In this review article, the critical challenge in the field of 4D bioprinting and transformations from 3D bioprinting to 4D phases is reviewed. Also, the mechanistic aspects from the chemistry and material science point of view are discussed too.
    Keywords:  3D printing; 4D bioprinting; drug delivery; hydrogels; smart polymers; soft robatics; tissue engineering
    DOI:  https://doi.org/10.1080/07388551.2023.2213398
  3. Expert Opin Drug Discov. 2023 Jul 11. 1-17
       INTRODUCTION: 3D printing, a versatile additive manufacturing technique, has diverse applications ranging from transportation, rapid prototyping, clean energy, and medical devices.
    AREAS COVERED: The authors focus on how 3D printing technology can enhance the drug discovery process through automating tissue production that enables high-throughput screening of potential drug candidates. They also discuss how the 3D bioprinting process works and what considerations to address when using this technology to generate cell laden constructs for drug screening as well as the outputs from such assays necessary for determining the efficacy of potential drug candidates. They focus on how bioprinting how has been used to generate cardiac, neural, and testis tissue models, focusing on bio-printed 3D organoids.
    EXPERT OPINION: The next generation of 3D bioprinted organ model holds great promises for the field of medicine. In terms of drug discovery, the incorporation of smart cell culture systems and biosensors into 3D bioprinted models could provide highly detailed and functional organ models for drug screening. By addressing current challenges of vascularization, electrophysiological control, and scalability, researchers can obtain more reliable and accurate data for drug development, reducing the risk of drug failures during clinical trials.
    Keywords:  Organoids; bioinks; bioprinting; cardiac; neural; stem cells
    DOI:  https://doi.org/10.1080/17460441.2023.2234280
  4. Adv Mater. 2023 Jul 11. e2302716
      Neural-vascular networks are densely distributed through periosteum, cortical bone and cancellous bone, which is of great significance for bone regeneration and remodeling. Although significant progresses have been made in bone tissue engineering, ineffective bone regeneration and delayed osteointegration still remains an issue due to the ignorance of intrabony nerves and blood vessels. Herein, inspired by space-filling polyhedron with open architectures, polyhedron-like scaffolds with spatial topologies were prepared via 3D printing technology to mimic the meshwork structure of cancellous bone. Benefiting from its spatial topologies, polyhedron-like scaffolds greatly promoted the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via activating PI3K-Akt signals, and exhibited satisfactory performance on angiogenesis and neurogenesis. Computational fluid dynamic (CFD) simulation elucidated that polyhedron-like scaffolds had a relatively lower area-weighted average static pressure, which is beneficial to osteogenesis. Furthermore, in vivo experiments further demonstrated that polyhedron-like scaffolds obviously promoted bone formation and osteointegration, as well as inducing vascularization and ingrowth of nerves, leading to innervated and vascularized bone regeneration. Taken together, this work offers a promising approach for fabricating multifunctional scaffolds without additional exogenous seeding cells and growth factors, which holds great potential for functional tissue regeneration and further clinical translation. This article is protected by copyright. All rights reserved.
    Keywords:  3d printing; bone regeneration; innervation; polyhedron-like scaffolds; vascularization
    DOI:  https://doi.org/10.1002/adma.202302716
  5. Front Bioeng Biotechnol. 2023 ;11 1186351
      Introduction: The problem of organs' shortage for transplantation is widely known: different manufacturing techniques such as Solvent casting, Electrospinning and 3D Printing were considered to produce bioartificial scaffolds for tissue engineering purposes and possible transplantation substitutes. The advantages of manufacturing techniques' combination to develop hybrid scaffolds with increased performing properties was also evaluated. Methods: Scaffolds were produced using poly-L-lactide-co-caprolactone (PLA-PCL) copolymer and characterized for their morphological, biological, and mechanical features. Results: Hybrid scaffolds showed the best properties in terms of viability (>100%) and cell adhesion. Furthermore, their mechanical properties were found to be comparable with the reference values for soft tissues (range 1-10 MPa). Discussion: The created hybrid scaffolds pave the way for the future development of more complex systems capable of supporting, from a morphological, mechanical, and biological standpoint, the physiological needs of the tissues/organs to be transplanted.
    Keywords:  3D printing; bioartificial scaffolds; electrospinning; organ transplant; soft tissue regeneration; tissue engineering; transplantology
    DOI:  https://doi.org/10.3389/fbioe.2023.1186351
  6. Nanomaterials (Basel). 2023 Jun 29. pii: 1976. [Epub ahead of print]13(13):
      Nowadays, treating corneal diseases arising from injury to the corneal endothelium necessitates donor tissue, but these corneas are extremely scarce. As a result, researchers are dedicating significant efforts to exploring alternative approaches that do not rely on donor tissues. Among these, creating a tissue-engineered scaffold on which corneal endothelial cells can be transplanted holds particular fascination. Numerous functional materials, encompassing natural, semi-synthetic, and synthetic polymers, have already been studied in this regard. In this review, we present a comprehensive overview of recent advancements in using polymer biomaterials as scaffolds for corneal endothelium tissue engineering. Initially, we analyze and present the key properties necessary for an effective corneal endothelial implant utilizing polymer biomaterials. Subsequently, we focus on various emerging biomaterials as scaffolds for corneal endothelium tissue engineering. We discuss their modifications (including natural and synthetic composites) and analyze the effect of micro- and nano-topological morphology on corneal endothelial scaffolds. Lastly, we highlight the challenges and prospects of these materials in corneal endothelium tissue engineering.
    Keywords:  biomaterials; corneal endothelium; tissue engineering; topography
    DOI:  https://doi.org/10.3390/nano13131976
  7. Tissue Eng Part B Rev. 2023 Jul 13.
      Polyurethane (PU) and PU ceramic scaffolds are the principal materials investigated for developing synthetic bone materials due to their excellent biocompatibility and biodegradability. PU has been combined with calcium phosphate (such as hydroxyapatite (HA) and tricalcium phosphate) to prepare scaffolds with enhanced mechanical properties and biocompatibility. This paper reviews the latest progress in the design, synthesis, modification, and biological attributes of HA/PU scaffolds for bone tissue engineering. Diverse HA/PU scaffolds have been proposed and discussed in terms of their osteogenic, antimicrobial, biocompatibility, and bioactivities. The application progress of HA/PU scaffolds in bone tissue engineering is predominantly introduced, including bone repair, bone defect filling, drug delivery, and long-term implants.
    DOI:  https://doi.org/10.1089/ten.TEB.2023.0073
  8. Molecules. 2023 Jun 25. pii: 4988. [Epub ahead of print]28(13):
      Hydrogels made from proteins are attractive materials for diverse medical applications, as they are biocompatible, biodegradable, and amenable to chemical and biological modifications. Recent advances in protein engineering, synthetic biology, and material science have enabled the fine-tuning of protein sequences, hydrogel structures, and hydrogel mechanical properties, allowing for a broad range of biomedical applications using protein hydrogels. This article reviews recent progresses on protein hydrogels with special focus on those made of microbially produced proteins. We discuss different hydrogel formation strategies and their associated hydrogel properties. We also review various biomedical applications, categorized by the origin of protein sequences. Lastly, current challenges and future opportunities in engineering protein-based hydrogels are discussed. We hope this review will inspire new ideas in material innovation, leading to advanced protein hydrogels with desirable properties for a wide range of biomedical applications.
    Keywords:  hydrogels; microbial expression; protein hydrogel; protein polymers; recombinant proteins; synthetic biology
    DOI:  https://doi.org/10.3390/molecules28134988