bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023‒09‒03
eleven papers selected by
Seerat Maqsood, University of Teramo

  1. Biotechnol Adv. 2023 Aug 28. pii: S0734-9750(23)00150-7. [Epub ahead of print] 108243
      3D bioprinting is a new 3D manufacturing technology, that can be used to accurately distribute and load microorganisms to form microbial active materials with multiple complex functions. Based on the 3D printing of human cells in tissue engineering, 3D bioprinting technology has been developed. Although 3D bioprinting technology is still immature, it shows great potential in the environmental field. Due to the precise programming control and multi-printing pathway, 3D bioprinting technology provides a high-throughput method based on micron-level patterning for a wide range of environmental microbiological engineering applications, which makes it an on-demand, multi-functional manufacturing technology. To date, 3D bioprinting technology has been employed in microbial fuel cells, biofilm material preparation, microbial catalysts and 4D bioprinting with time dimension functions. Nevertheless, current 3D bioprinting technology faces technical challenges in improving the mechanical properties of materials, developing specific bioinks to adapt to different strains, and exploring 4D bioprinting for intelligent applications. Hence, this review systematically analyzes the basic technical principles of 3D bioprinting, bioinks materials and their applications in the environmental field, and proposes the challenges and future prospects of 3D bioprinting in the environmental field. Combined with the current development of microbial enhancement technology in the environmental field, 3D bioprinting will be developed into an enabling platform for multifunctional microorganisms and facilitate greater control of in situ directional reactions.
    Keywords:  3D bioprinting; Microbial immobilization; Structured biomaterials
  2. JACS Au. 2023 Aug 28. 3(8): 2086-2106
      Three-dimensional (3D) bioprinting technologies involving photopolymerizable bioinks (PBs) have attracted enormous attention in recent times owing to their ability to recreate complex structures with high resolution, mechanical stability, and favorable printing conditions that are suited for encapsulating cells. 3D bioprinted tissue constructs involving PBs can offer better insights into the tumor microenvironment and offer platforms for drug screening to advance cancer research. These bioinks enable the incorporation of physiologically relevant cell densities, tissue-mimetic stiffness, and vascularized channels and biochemical gradients in the 3D tumor models, unlike conventional two-dimensional (2D) cultures or other 3D scaffold fabrication technologies. In this perspective, we present the emerging techniques of 3D bioprinting using PBs in the context of cancer research, with a specific focus on the efforts to recapitulate the complexity of the tumor microenvironment. We describe printing approaches and various PB formulations compatible with these techniques along with recent attempts to bioprint 3D tumor models for studying migration and metastasis, cell-cell interactions, cell-extracellular matrix interactions, and drug screening relevant to cancer. We discuss the limitations and identify unexplored opportunities in this field for clinical and commercial translation of these emerging technologies.
  3. Adv Mater. 2023 Sep 01. e2305911
      3D-bioprinting is a promising technology to produce human tissues as drug screening tool or for organ repair. However, direct printing of living cells has proven difficult. Here, we present a method to directly 3D-bioprint human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes embedded in a collagen-hyaluronic acid ink generating centimeter-sized functional ring- and ventricle-shaped cardiac tissues in an accurate and reproducible manner. The printed tissues contained hiPSC-derived cardiomyocytes with well-organized sarcomeres and exhibited spontaneous and regular contractions, which persisted for several months and were able to contract against passive resistance. Importantly, beating frequencies of the printed cardiac tissues could be modulated by pharmacological stimulation. This approach opens up new possibilities for generating complex functional cardiac tissues as models for advanced drug screening or as tissue grafts for organ repair or replacement. This article is protected by copyright. All rights reserved.
    Keywords:  3D-bioprinting; cardiac tissue engineering; heart; human induced pluripotent stem cells; in-gel printing; support bath
  4. J Biol Eng. 2023 Aug 29. 17(1): 56
      The use of biodegradable polymers for treating bone-related diseases has become a focal point in the field of biomedicine. Recent advancements in material technology have expanded the range of materials suitable for orthopaedic implants. Three-dimensional (3D) printing technology has become prevalent in healthcare, and while organ printing is still in its early stages and faces ethical and technical hurdles, 3D printing is capable of creating 3D structures that are supportive and controllable. The technique has shown promise in fields such as tissue engineering and regenerative medicine, and new innovations in cell and bio-printing and printing materials have expanded its possibilities. In clinical settings, 3D printing of biodegradable metals is mainly used in orthopedics and stomatology. 3D-printed patient-specific osteotomy instruments, orthopedic implants, and dental implants have been approved by the US FDA for clinical use. Metals are often used to provide support for hard tissue and prevent complications. Currently, 70-80% of clinically used implants are made from niobium, tantalum, nitinol, titanium alloys, cobalt-chromium alloys, and stainless steels. However, there has been increasing interest in biodegradable metals such as magnesium, calcium, zinc, and iron, with numerous recent findings. The advantages of 3D printing, such as low manufacturing costs, complex geometry capabilities, and short fabrication periods, have led to widespread adoption in academia and industry. 3D printing of metals with controllable structures represents a cutting-edge technology for developing metallic implants for biomedical applications. This review explores existing biomaterials used in 3D printing-based orthopedics as well as biodegradable metals and their applications in developing metallic medical implants and devices. The challenges and future directions of this technology are also discussed.
    Keywords:  3D printing; Bioactive materials; Biodegradable metals; Orthopaedic therapies; Polymer composites
  5. Biomater Adv. 2023 Aug 14. pii: S2772-9508(23)00311-4. [Epub ahead of print]154 213588
      Replacement therapy for the salivary gland (SG) remains an unmet clinical need. Xerostomia ("dry mouth") due to hyposalivation can result from injury or disease to the SG, such as salivary acinar death caused by radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC). Currently, only palliative treatments exist for xerostomia, and many patients endure deteriorated oral health and poor quality of life. Tissue engineering could offer a permanent solution for SG replacement by isolating healthy SG tissues prior to RT, expanding its cells in vitro, and recreating a functional salivary neogland for implantation post-RT. 3D bioprinting methods potentiate spatial cell deposition into defined hydrogel-based architectures, mimicking the thin epithelia developed during the complex branching morphogenesis of SG. By leveraging a microfluidics-based bioprinter with coaxial polymer and crosslinker streams, we fabricated thin, biocompatible, and reproducible hydrogel features that recapitulate the thin epithelia characteristics of SG. This flexible platform enabled two modes of printing: we produced solid hydrogel fibers, with diameters <100 μm, that could be rastered to create larger mm-scale structures. By a second method, we generated hollow tubes with wall thicknesses ranging 45-80 μm, total tube diameters spanning 0.6-2.2 mm, and confirmed tube patency. In both cases, SG cells could be printed within the thin hydrogel features, with preserved phenotype and high viability, even at high density (5.0 × 106 cells/mL). Our work demonstrates hydrogel feature control across multiple length scales, and a new paradigm for addressing SG restoration by creating microscale tissue engineered components.
    Keywords:  3D bioprinting; Biomaterials; Hydrogels; Salivary gland; Sodium alginate; Tissue engineering
  6. Front Bioeng Biotechnol. 2023 ;11 1258666
      Substantial interests have been attracted to multiple bioactive and biomimetic biomaterials in recent decades because of their ability in presenting a structural and functional reconstruction of urinary tissues. Some innovative technologies have also been surging in urinary tissue engineering and urological regeneration by providing insights into the physiological behavior of the urinary system. As such, the hierarchical structure and tissue function of the bladder, urethra, and ureter can be reproduced similarly to the native urinary tissues. This review aims to summarize recent advances in functional biomaterials and biomimetic technologies toward urological reconstruction. Various nanofirous biomaterials derived from decellularized natural tissues, synthetic biopolymers, and hybrid scaffolds were developed with desired microstructure, surface chemistry, and mechanical properties. Some growth factors, drugs, as well as inorganic nanomaterials were also utilized to enhance the biological activity and functionality of scaffolds. Notably, it is emphasized that advanced approaches, such as 3D (bio) printing and organoids, have also been developed to facilitate structural and functional regeneration of the urological system. So in this review, we discussed the fabrication strategies, physiochemical properties, and biofunctional modification of regenerative biomaterials and their potential clinical application of fast-evolving technologies. In addition, future prospective and commercial products are further proposed and discussed.
    Keywords:  biomaterials; reconstruction; technology; tissue engineering; urinary
  7. Regen Biomater. 2023 ;10 rbad067
      Reconstruction of bone defects remains a clinical challenge, and 3D bioprinting is a fabrication technology to treat it via tissue engineering. Collagen is currently the most popular cell scaffold for tissue engineering; however, a shortage of printability and low mechanical strength limited its application via 3D bioprinting. In the study, aiding with a gelatin support bath, a collagen-based scaffold was fabricated via 3D printing, where hydroxyapatite (HAP) and bone marrow mesenchymal stem cells (BMSCs) were added to mimic the composition of bone. The results showed that the blend of HAP and collagen showed suitable rheological performance for 3D extrusion printing and enhanced the composite scaffold's strength. The gelatin support bath could effectively support the HAP/collagen scaffold's dimension with designed patterns at room temperature. BMSCs in/on the scaffold kept living and proliferating, and there was a high alkaline phosphate expression. The printed collagen-based scaffold with biocompatibility, mechanical properties and bioactivity provides a new way for bone tissue engineering via 3D bioprinting.
    Keywords:  3D printing; collagen; gelation bath; hydroxyapatite; scaffold
  8. Sci Rep. 2023 08 29. 13(1): 14120
      As a bone tissue engineering material, polylactic acid (PLA) has received significant attention and interest due to its ease of processing and biocompatibility. However, its insufficient mechanical properties and poor wettability are two major drawbacks that limit its extensive use. For this purpose, the present study uses in-situ cold argon plasma treatment coupled with a fused deposition modeling printer to enhance the physio-mechanical and biological behavior of 3D-printed PLA scaffolds. Following plasma treatment, field emission scanning electron microscopy images indicated that the surface of the modified scaffold became rough, and the interlayer bonding was enhanced. This resulted in an improvement in the tensile properties of samples printed in the X, Y, and Z directions, with the enhancement being more significant in the Z direction. Additionally, the root mean square value of PLA scaffolds increased (up to 70-fold) after plasma treatment. X-ray photoelectron spectroscopy analysis demonstrated that the plasma technique increased the intensity of oxygen-containing bonds, thereby reducing the water contact angle from 92.5° to 42.1°. The in-vitro degradation study also demonstrated that argon plasma treatment resulted in a 77% increase in PLA scaffold degradation rate. Furthermore, the modified scaffold improved the viability, attachment, and proliferation of human adipose-derived stem cells. These findings suggest that in-situ argon plasma treatment may be a facile and effective method for improving the properties of 3D-printed parts for bone tissue engineering and other applications.
  9. J Craniofac Surg. 2023 Aug 28.
      Bone tissue regeneration is a complex process that proceeds along the well-established wound healing pathway of hemostasis, inflammation, proliferation, and remodeling. Recently, tissue engineering efforts have focused on the application of biological and technological principles for the development of soft and hard tissue substitutes. Aim is directed towards boosting pathways of the healing process to restore form and function of tissue deficits. Continued development of synthetic scaffolds, cell therapies, and signaling biomolecules seeks to minimize the need for autografting. Despite being the current gold standard treatment, it is limited by donor sites' size and shape, as well as donor site morbidity. Since the advent of computer-aided design/computer-aided manufacturing (CAD/CAM) and additive manufacturing (AM) techniques (3D printing), bioengineering has expanded markedly while continuing to present innovative approaches to oral and craniofacial skeletal reconstruction. Prime examples include customizable, high-strength, load bearing, bioactive ceramic scaffolds. Porous macro- and micro-architecture along with the surface topography of 3D printed scaffolds favors osteoconduction and vascular in-growth, as well as the incorporation of stem and/or other osteoprogenitor cells and growth factors. This includes platelet concentrates (PCs), bone morphogenetic proteins (BMPs), and some pharmacological agents, such as dipyridamole (DIPY), an adenosine A2A receptor indirect agonist that enhances osteogenic and osteoinductive capacity, thus improving bone formation. This two-part review commences by presenting current biological and engineering principles of bone regeneration utilized to produce 3D-printed ceramic scaffolds with the goal to create a viable alternative to autografts for craniofacial skeleton reconstruction. Part II comprehensively examines recent preclinical data to elucidate the potential clinical translation of such 3D-printed ceramic scaffolds.
  10. Tissue Eng Part B Rev. 2023 Aug 30.
      The intestine is a visceral organ that integrates absorption, metabolism, and immunity, which is vulnerable to external stimulus. Researchers in the fields such as food science, immunology and pharmacology have committed to developing appropriate in vitro intestinal cell models to study the intestinal absorption and metabolism mechanisms of various nutrients and drugs, or pathogenesis of intestinal diseases. In the past three decades, the intestinal cell models have undergone a significant transformation from conventional two-dimensional (2D) cultures to three-dimensional (3D) systems, and the achievements of 3D cell culture have been greatly contributed by the fabrication of different scaffolds. In this review, we first introduce the developing trend of existing intestinal models. Then, four types of scaffolds, including Transwell, hydrogel, tubular scaffolds and intestine-on-a-chip are discussed for their 3D structure, composition, advantages, and limitations in the establishment of intestinal cell models. Excitingly, some of the in vitro intestinal cell models based on these scaffolds could successfully mimic the 3D structure, microenvironment, mechanical peristalsis, fluid system, signaling gradients or other important aspects of the original human intestine. Furthermore, we discuss the potential applications of the intestinal cell models in drug screening, disease modeling and even regenerative repair of intestinal tissues. This review presents an overview of state-of-the-art scaffold-based cell models within the context of intestines, and highlights their major advances and applications contributing to a better knowledge of intestinal diseases.
  11. Adv Healthc Mater. 2023 Sep 01. e2301692
      The reconstruction of critical-size bone defects in long bones remains a challenge for clinicians. We developed a new bioactive medical device for long bone repair by combining a 3D-printed architectured cylindrical scaffold made of clinical-grade polylactic acid (PLA) with a polyelectrolyte film coating delivering the osteogenic bone morphogenetic protein 2 (BMP-2). This film-coated scaffold was used to repair a sheep metatarsal 25-mm long critical-size bone defect. In vitro and in vivo biocompatibility of the film-coated PLA material were proved according to ISO standards. Scaffold geometry was found to influence BMP-2 incorporation. Bone regeneration was followed using X-ray scans, μCT scans, and histology. We showed that scaffold internal geometry, notably pore shape, influenced bone regeneration, which was homogenous longitudinally. Scaffolds with cubic pores of ∼870 μm and a low BMP-2 dose of ∼120 μg/cm3 induced the best bone regeneration without any adverse effects. The visual score given by clinicians during animal follow-up was found to be an easy way to predict bone regeneration. This work opens perspectives for a clinical application in personalized bone regeneration. This article is protected by copyright. All rights reserved.
    Keywords:  3D printing; bone tissue engineering; large animal model; medical devices; surface coatings