bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023‒10‒22
eleven papers selected by
Seerat Maqsood, University of Teramo

  1. Int J Ophthalmol. 2023 ;16(10): 1702-1711
      Three-dimensional (3D) bioprinting is widely used in ophthalmic clinic, including in diagnosis, surgery, prosthetics, medications, drug development and delivery, and medical education. Articles published in 2011-2022 into bioinks, printing technologies, and bioprinting applications in ophthalmology were reviewed and the strengths and limitations of bioprinting in ophthalmology highlighted. The review highlighted the trade-offs of printing technologies and bioinks in respect to, among others, material type cost, throughput, gelation technique, cell density, cell viability, resolution, and printing speed. There is already widespread ophthalmological application of bioprinting outside clinical settings, including in educational modelling, retinal imaging/visualization techniques and drug design/testing. In clinical settings, bioprinting has already found application in pre-operatory planning. Even so, the findings showed that even with its immense promise, actual translation to clinical applications remains distant, but relatively closer for the corneal (except stromal) tissues, epithelium, endothelium, and conjunctiva, than it was for the retina. This review similarly reflected on the critical on the technical, practical, ethical, and cost barrier to rapid progress of bioprinting in ophthalmology, including accessibility to the most sophisticated bioprinting technologies, choice, and suitability of bioinks, tissue viability and storage conditions. The extant research is encouraging, but more work is clearly required for the push towards clinical translation of research.
    Keywords:  3D bioprinting; bioinks; bioprinting; ocular bioprinting; ophthalmologic bioprinting
  2. Biotechnol Adv. 2023 Oct 18. pii: S0734-9750(23)00180-5. [Epub ahead of print] 108273
      The long duration space missions across the Low Earth Orbit (LEO) often expose the voyagers to an abrupt zero gravity influence. The severe extraterrestrial cosmic radiation directly causes a plethora of moderate to chronic healthcare crises. The only feasible solution to manage critical injuries on board is surgical interventions or immediate return to Earth. This led the group of space medicine practitioners to adopt principles from tissue engineering and develop human tissue equivalents as an immediate regenerative therapy on board. The current review explicitly demonstrates the constructive application of different tissue-engineered equivalents matured under the available ground-based microgravity simulation facilities. Further, it elucidates how augmenting the superiority of biomaterial-based 3D bioprinting technology can enhance their clinical applicability. Additionally, the regulatory role of weightlessness condition on the underlying cellular signaling pathways governing tissue morphogenesis has been critically discussed. This information will provide future directions on how 3D biofabrication can be used as a plausible tool for healing on-flight chronic health emergencies. Thus, in our review, we aimed to precisely debate whether 3D biofabrication is deployed to cater to on-flight healthcare anomalies or space-like conditions are being utilized for generating 3D bioprinted human tissue constructs for efficient drug screening and regenerative therapy.
    Keywords:  3D bioprinting; Cell signaling pathw; Microgravity; Space; Tissue engineering
  3. Res Pharm Sci. 2023 Sep-Oct;18(5):18(5): 566-579
      Background and purpose: Biomaterials, scaffold manufacturing, and design strategies with acceptable mechanical properties are the most critical challenges facing tissue engineering.Experimental approach: In this study, polycaprolactone (PCL) scaffolds were fabricated through a novel three-dimensional (3D) printing method. The PCL scaffolds were then coated with 2% agarose (Ag) hydrogel. The 3D-printed PCL and PCL/Ag scaffolds were characterized for their mechanical properties, porosity, hydrophilicity, and water absorption. The construction and morphology of the printed scaffolds were evaluated via Fourier-Transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The attachment and proliferation of L929 cells cultured on the scaffolds were investigated through MTT assay on the cell culture study upon the 1st, 3rd, and 7th days.
    Findings/Results: The incorporation of Ag hydrogel with PCL insignificantly decreased the mechanical strength of the scaffold. The presence of Ag enhanced the hydrophilicity and water absorption of the scaffolds, which could positively influence their cell behavior compared to the PCL scaffolds. Regarding cell morphology, the cells on the PCL scaffolds had a more rounded shape and less cell spreading, representing poor cell attachment and cell-scaffold interaction due to the hydrophobic nature of PCL. Conversely, the cells on the PCL/Ag scaffolds were elongated with a spindle-shaped morphology indicating a positive cell-scaffold interaction.
    Conclusion and implications: PCL/Ag scaffolds can be considered appropriate for tissue-engineering applications.
    Keywords:  3D printing; Agarose; Polycaprolactone; Tissue engineering
  4. Biomed Pharmacother. 2023 Oct 17. pii: S0753-3322(23)01513-5. [Epub ahead of print]168 115715
      Osteoarthritis (OA) is a challenging joint inflammatory disease that often leads to disability. Immunoregulatory Exosomes (Exos) have shown promise in OA and cartilage degeneration treatment. Engineering Exos to deliver therapeutic agents like Kartogenin (KGN) has displayed potential for restoring cartilage regeneration. However, challenges include the uneven distribution of Exos at the injury site and the release of Exos cargo out of chondrocytes. Hydrogel-loaded uMSC-Exo has demonstrated significant therapeutic effects in wound healing and tissue regeneration. Recently, a new version of three-dimensional (3D) bioprinting of hydrogel significantly restored cartilage regeneration in OA joints. Combining immune regulatory Exos with 3D bioprinting hydrogel (3D-BPH-Exos) holds the potential for immunomodulating cartilage tissue and treatment of OA. It can reduce intracellular inflammasome formation and the release of inflammatory agents like IL-1β, TNF-α, and INF-γ, while also preventing chondrocyte apoptosis by restoring mitochondrial functions and enhancing chondrogenesis in synovial MSCs, osteoprogenitor cells, and osteoclasts. Loading Exos with chondrogenic stimuli agents in the 3D-BPH-Exos approach may offer a faster and safer strategy for cartilage repair while better inhibiting joint inflammation than high doses of anti-inflammatory drugs and cell-based therapies. This review provides a comprehensive overview of hydrogel bioprinting and exosome-based therapy in OA. It emphasizes the potential of 3D-BPH-Exos loaded with chondrogenic stimuli agents for OA treatment, serving as a basis for further research.
    Keywords:  3D bioprinting hydrogel; Cartilage repair; Exosomes; Osteoarthritis
  5. J Vis Exp. 2023 Sep 29.
      For a cell model to be viable for drug screening, the system must meet throughput and homogeneity requirements alongside having an efficient development time. However, many published 3D models do not satisfy these criteria. This therefore, limits their usefulness in early drug discovery applications. Three-dimensional (3D) bioprinting is a novel technology that can be applied to the development of 3D models to expedite development time, increase standardization, and increase throughput. Here, we present a protocol to develop 3D bioprinted coculture models of human induced pluripotent stem cell (iPSC)-derived glutamatergic neurons and astrocytes. These cocultures are embedded within a hydrogel matrix of bioactive peptides, full-length extracellular matrix (ECM) proteins, and with a physiological stiffness of 1.1 kPa. The model can be rapidly established in 96-well and 384-well formats and produces an average post-print viability of 72%. The astrocyte-to-neuron ratio in this model is shown to be 1:1.5, which is within the physiological range for the human brain. These 3D bioprinted cell populations also show expression of mature neural cell type markers and growth of neurite and astrocyte projections within 7 days of culture. As a result, this model is suitable for analysis using cell dyes and immunostaining techniques alongside neurite outgrowth assays. The ability to produce these physiologically representative models at scale makes them ideal for use in medium-to-high throughput screening assays for neuroscience targets.
  6. Biomacromolecules. 2023 Oct 16.
      Taking inspiration from spider silk protein spinning, we developed a method to produce tough filaments using extrusion-based 3D bioprinting and salting-out of the protein. To enhance both stiffness and ductility, we have designed a blend of partially crystalline, thermally sensitive natural polymer gelatin and viscoelastic G-polymer networks, mimicking the components of spider silk. Additionally, we have incorporated inorganic nanoparticles as a rheological modifier to fine-tune the 3D printing properties. This self-healing nanocomposite hydrogel exhibits exceptional mechanical properties, biocompatibility, shear thinning behavior, and a well-controlled gelation mechanism for 3D printing.
  7. N Biotechnol. 2023 Oct 15. pii: S1871-6784(23)00058-4. [Epub ahead of print]
      Personalized 3D printed scaffolds are a new generation of implants for tissue engineering and regenerative medicine purposes. Scaffolds support cell growth, providing an artificial extracellular matrix for tissue repair and regeneration and can biodegrade once cells have assumed their physiological and structural roles. The ethical challenges and opportunities of these implants should be mapped in parallel with the life cycle of the scaffold to assist their development and implementation in a responsible, safe, and ethically sound manner. This article provides an overview of these relevant ethical aspects. We identified nine themes which were linked to three stages of the life cycle of the scaffold: the development process, clinical testing, and the implementation process. The described ethical issues are related to good research and clinical practices, such as privacy issues concerning digitalization, first-in-human trials, responsibility and commercialization. At the same time, this article also creates awareness for underexplored ethical issues, such as irreversibility, embodiment and the ontological status of these scaffolds. Moreover, it exemplifies how to include gender in the ethical assessment of new technologies. These issues are important for responsible development and implementation of personalized 3D printed scaffolds and in need of more attention within the additive manufacturing and tissue engineering field. Moreover, the insights of this review reveal unresolved qualitative empirical and normative questions that could further deepen the understanding and co-creation of the ethical implications of this new generation of implants.
    Keywords:  3D printing; ethics; implants; regenerative medicine; scaffolds; tissue engineering
  8. ACS Biomater Sci Eng. 2023 Oct 19.
      New horizons in cardiovascular research are opened by using 3D printing for biodegradable implants. This additive manufacturing approach allows the design and fabrication of complex structures according to the patient's imaging data in an accurate, reproducible, cost-effective, and quick manner. Acellular cardiovascular implants produced from biodegradable materials have the potential to provide enough support for in situ tissue regeneration while gradually being replaced by neo-autologous tissue. Subsequently, they have the potential to prevent long-term complications. In this Review, we discuss the current status of 3D printing applications in the development of biodegradable cardiovascular implants with a focus on design, biomaterial selection, fabrication methods, and advantages of implantable controlled release systems. Moreover, we delve into the intricate challenges that accompany the clinical translation of these groundbreaking innovations, presenting a glimpse of potential solutions poised to enable the realization of these technologies in the realm of cardiovascular medicine.
    Keywords:  3D printing; additive manufacturing; clinical translation; controlled release system; drug delivery; heart valve; regulatory challenges; vascular graft; vascular stent
  9. Front Bioeng Biotechnol. 2023 ;11 1256361
      The rapid advancement of 3D printing has transformed industries, including medicine and pharmaceuticals. Integrating antioxidants into 3D-printed structures offers promising therapeutic strategies for enhanced antioxidant delivery. This review explores the synergistic relationship between 3D printing and antioxidants, focusing on the design and fabrication of antioxidant-loaded constructs. Incorporating antioxidants into 3D-printed matrices enables controlled release and localized delivery, improving efficacy while minimizing side effects. Customization of physical and chemical properties allows tailoring of antioxidant release kinetics, distribution, and degradation profiles. Encapsulation techniques such as direct mixing, coating, and encapsulation are discussed. Material selection, printing parameters, and post-processing methods significantly influence antioxidant release kinetics and stability. Applications include wound healing, tissue regeneration, drug delivery, and personalized medicine. This comprehensive review aims to provide insights into 3D printing-assisted antioxidant delivery systems, facilitating advancements in medicine and improved patient outcomes for oxidative stress-related disorders.
    Keywords:  3D printing; antioxidants; controlled release; oxidative stress-related disorders; therapeutic strategies
  10. Drug Deliv Transl Res. 2023 Oct 18.
      A major clinical challenge today is the large number of bone defects caused by diseases or trauma. The development of three-dimensional (3D) scaffolds with adequate properties is crucial for successful bone repair. In this study, we prepared biomimetic mesoporous bioactive glass (MBG)-based scaffolds with and without ceria addition (up to 3 mol %) to explore the biological structure and chemical composition of the marine sponge Spongia Agaricina (SA) as a sacrificial template. Micro-CT examination revealed that all scaffolds exhibited a highly porous structure with pore diameters primarily ranging from 143.5 μm to 213.5 μm, facilitating bone ingrowth. Additionally, smaller pores (< 75 μm), which are known to enhance osteogenesis, were observed. The undoped scaffold displayed the highest open porosity value of 90.83%. Cytotoxicity assessments demonstrated that all scaffolds were noncytotoxic and nongenotoxic toward osteoblast cells. Moreover, scaffolds with higher CeO2 content promoted osteogenic differentiation of dental pulp stem cells, stimulating calcium and osteocalcin secretion. The scaffolds also exhibited antimicrobial and antibiofilm effects against Staphylococcus aureus (S. aureus) as well as drug delivery ability. Our research findings indicated that the combination of MBG, natural biological structure, and the addition of Ce exhibited a synergistic effect on the structure and biological properties of scaffolds for applications in bone tissue engineering.
    Keywords:  3D scaffolds; Antimicrobial activity; Bone regeneration; Ce-doped bioactive glasses; Drug delivery