bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023–12–17
fourteen papers selected by
Seerat Maqsood, University of Teramo



  1. Zhonghua Yan Ke Za Zhi. 2023 Dec 11. 59(12): 1065-1068
      On the basis of 3D printing technology, 3D bioprinting has emerged with great development potential and good prospects in the field of medicine and tissue engineering. With this technique, different types of cells and biomaterials can be precisely incorporated into 3D anatomical structures, achieving tissue substitutes with superior structures or functions. In recent years, great progress has been made in the application of 3D bioprinting in ophthalmology. This article reviews not only the differences between 3D printing and 3D bioprinting, but also the development, types, characteristics, application, and prospects of 3D bioprinting in the production of eye tissue engineering materials.
    DOI:  https://doi.org/10.3760/cma.j.cn112142-20230716-00003
  2. Materials (Basel). 2023 Nov 30. pii: 7461. [Epub ahead of print]16(23):
      The emergence of additive manufacturing, commonly referred to as 3D printing, has led to a revolution in the field of biofabrication. Numerous types of 3D bioprinting, including extrusion bioprinting, inkjet bioprinting, and lithography-based bioprinting, have been developed and have played pivotal roles in driving a multitude of pioneering breakthroughs in the fields of tissue engineering and regenerative medicine. Among all the 3D bioprinting methods, light-based bioprinting utilizes light to crosslink or solidify photoreactive biomaterials, offering unprecedented spatiotemporal control over biomaterials and enabling the creation of 3D structures with extremely high resolution and precision. However, the lack of suitable photoactive biomaterials has hindered the application of light-based bioprinting in tissue engineering. The development of photoactive biomaterials has only recently been expanded. Therefore, this review summarizes the latest advancements in light-based 3D bioprinting technologies, including the development of light-based bioprinting techniques, photo-initiators (PIs), and photoactive biomaterials and their corresponding applications. Moreover, the challenges facing bioprinting are discussed, and future development directions are proposed.
    Keywords:  biocompatibility; hydrogel; light-based 3D bioprinting; photoactive biomaterials; photopolymerization; tissue engineering
    DOI:  https://doi.org/10.3390/ma16237461
  3. ACS Appl Bio Mater. 2023 Dec 13.
      3D bioprinting is recognized as a promising biomanufacturing technology that enables the reproducible and high-throughput production of tissues and organs through the deposition of different bioinks. Especially, bioinks based on loaded cells allow for immediate cellularity upon printing, providing opportunities for enhanced cell differentiation for organ manufacturing and regeneration. Thus, extensive applications have been found in the field of tissue engineering. The performance of the bioinks determines the functionality of the entire printed construct throughout the bioprinting process. It is generally expected that bioinks should support the encapsulated cells to achieve their respective cellular functions and withstand normal physiological pressure exerted on the printed constructs. The bioinks should also exhibit a suitable printability for precise deposition of the constructs. These characteristics are essential for the functional development of tissues and organs in bioprinting and are often achieved through the combination of different biomaterials. In this review, we have discussed the cutting-edge outstanding performance of different bioinks for printing various human tissues and organs in recent years. We have also examined the current status of 3D bioprinting and discussed its future prospects in relieving or curing human health problems.
    Keywords:  3D bioprinting; bioink; organs; regeneration; tissue engineering
    DOI:  https://doi.org/10.1021/acsabm.3c00806
  4. Biomater Adv. 2023 Dec 09. pii: S2772-9508(23)00448-X. [Epub ahead of print]156 213725
      
    DOI:  https://doi.org/10.1016/j.bioadv.2023.213725
  5. Int Wound J. 2023 Dec 09.
      Advancements in 3D bioprinting, particularly the use of gelatin methacrylate (GelMA) hydrogels, are ushering in a transformative era in regenerative medicine and tissue engineering. This review highlights the pivotal role of GelMA hydrogels in wound healing and skin regeneration. Its biocompatibility, tunable mechanical properties and support for cellular proliferation make it a promising candidate for bioactive dressings and scaffolds. Challenges remain in optimizing GelMA hydrogels for clinical use, including scalability of 3D bioprinting techniques, durability under physiological conditions and the development of advanced bioinks. The review covers GelMA's applications from enhancing wound dressings, promoting angiogenesis and facilitating tissue regeneration to addressing microbial infections and diabetic wound healing. Preclinical studies underscore GelMA's potential in tissue healing and the need for further research for real-world applications. The future of GelMA hydrogels lies in overcoming these challenges through multidisciplinary collaboration, advancing manufacturing techniques and embracing personalized medicine paradigms.
    Keywords:  3D bioprinting; GelMA hydrogels; regenerative medicine; tissue engineering; wound healing
    DOI:  https://doi.org/10.1111/iwj.14533
  6. Tissue Eng Part A. 2023 Dec 08.
      3D bioprinting, a promising advancement in tissue engineering technology, involves the robotic, layer-by-layer additive biofabrication of functional 3D tissue and organ constructs. This process utilizes biomaterials, typically hydrogels and living cells, following digital models. Traditional tissue engineering employs a classic triad of living cells, scaffolds, and physicochemical signals in bioreactors. A scaffold is a temporary, often biodegradable, support structure. Tissue engineering primarily falls into two categories: i) scaffold-based and ii) scaffold-free. The latter, scaffold-free 3D bioprinting, is gaining increasing popularity. Organ building blocks (OBB), capable of self-assembly and self-organization, such as tissue spheroids, organoids, and assembloids, have begun to be utilized in scaffold-free bioprinting. This paper discusses the expanding range of OBB, presents the rapidly evolving collection of bioprinting and bioassembly methods using these OBB, and finally, outlines the advantages, challenges, and future perspectives of employing OBB in organ printing.
    DOI:  https://doi.org/10.1089/ten.TEA.2023.0198
  7. Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023 1-4
      Tissue engineering scaffolds require complex networks for nutrient diffusion and cell attachment. They must have specific surface area and curvature, and often need a multimaterial composition, demanding advanced micro-fabrication methods. 3D extrusion bioprinting offers versatility to manufacture different scaffold, and strategies for multimaterial printing have been introduced. We propose a method to fabricate scaffolds based on gyroid-helical-patterned microfibers, providing a platform to study the effect of the gyroid minimum curvature on cellular processes, since the geometry wont be layer-by-layer approximated. The pattern is obtained by mixing inks using a gyroid-helix shaped rotational mixer, modifying the extruder of a conventional 3D printer. The mixer was simulated using computational fluid dynamics tools, varying the volumetric flow to obtain different gyroid-thickness. Due to its surface area minimization, it shows lower energy requirements than state-of-art fluid mixers, with a pressure drop of 1.7%, a power number of 39, and a rotation-induced shear stress of ∼400 Pa, enabling the use of cell-embedded bioinks.
    DOI:  https://doi.org/10.1109/EMBC40787.2023.10340622
  8. Mater Today Bio. 2023 Dec;23 100872
      Tissue-engineered bone substitutes, characterized by favorable physicochemical, mechanical, and biological properties, present a promising alternative for addressing bone defects. In this study, we employed an innovative 3D host-guest scaffold model, where the host component served as a mechanical support, while the guest component facilitated osteogenic effects. More specifically, we fabricated a triangular porous polycaprolactone framework (host) using advanced 3D printing techniques, and subsequently filled the framework's pores with tragacanth gum-45S5 bioactive glass as the guest component. Comprehensive assessments were conducted to evaluate the physical, mechanical, and biological properties of the designed scaffolds. Remarkably, successful integration of the guest component within the framework was achieved, resulting in enhanced bioactivity and increased strength. Our findings demonstrated that the scaffolds exhibited ion release (Si, Ca, and P), surface apatite formation, and biodegradation. Additionally, in vitro cell culture assays revealed that the scaffolds demonstrated significant improvements in cell viability, proliferation, and attachment. Significantly, the multi-compartment scaffolds exhibited remarkable osteogenic properties, indicated by a substantial increase in the expression of osteopontin, osteocalcin, and matrix deposition. Based on our results, the framework provided robust mechanical support during the new bone formation process, while the guest component matrix created a conducive micro-environment for cellular adhesion, osteogenic functionality, and matrix production. These multi-compartment scaffolds hold great potential as a viable alternative to autografts and offer promising clinical applications for bone defect repair in the future.
    Keywords:  3D models; Bone; Framework; Guest component; Multi-compartment scaffold
    DOI:  https://doi.org/10.1016/j.mtbio.2023.100872
  9. Int J Biol Macromol. 2023 Dec 11. pii: S0141-8130(23)05653-2. [Epub ahead of print] 128754
      3D printing was used to prepare implantable systems or tablets loaded with dolutegravirto to explore their potential as long-acting implantables (LAIs). Our strategy relies on preparing a polylactide (PLA) filament loaded with the anti-HIV drug. Subsequently, 3D printing was performed under conditions that allowed the PLA to be simultaneously melted and the drug encapsulated within the printed strand. The dolutegravir release profiles indicated its sustained release for 47 days. Furthermore, neat and drug-loaded tablets were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), while their morphology was assessed by scanning electron microscopy (SEM). Finally, their biocompatibility was proved by MTT assay against ISO standards recommended L929 mouse and human Hs68 skin fibroblast cells. All the results indicated that the 3D printing of PLA-based tablets could produce customized medications with potential applications against HIV.
    Keywords:  3D-printing; Anti-HIV materials; Drug delivery systems; Long-acting injectable; PLA
    DOI:  https://doi.org/10.1016/j.ijbiomac.2023.128754
  10. Expert Opin Drug Deliv. 2023 Dec 11. 1-19
       INTRODUCTION: 3D printing (3DP) applications in medicine are intensively investigated, creating an opportunity to provide patient-tailored therapy by delivering a drug with an accurate dose and release profile. Moving away from the 'one size fits all' paradigm, it could be beneficial for treating mental and neurological disorders, improving the efficiency and safety of the therapy. The aim of this critical review is to assess recent advances and identify gaps regarding 3DP in this important and challenging field, by focusing on recent research examples.
    AREAS COVERED: Applications of the 3DP techniques for solid dosage forms in mental and neurological disorders have been covered and discussed, together with recent advantages, limitations, and future directions.
    EXPERT OPINION: The personalize treatment, which is considered as the most significant advantage of the 3DP technique, can be beneficial in mental and neurological disorders therapy, where the dose should be adjusted to the patient. Printing of medicines enables creating the structure modifications and thus controlling the drug release or combining multiple drugs into one tablet, simplifying the dose regimen. Medications printed on-demand, in health-care facilities, could address the special needs of pediatric patients and help avoid interruptions in the supply chain. Despite promising advances, the described methods have limitations and need further investigation before being scaled-up to an industrial manufacturing environment. There is also a need to establish protocols for the preparation and registration of 3DP dosage forms.
    Keywords:  3D printing; Mental disorders; additive manufacturing; neurological disorders; personalized medicine; solid dosage forms
    DOI:  https://doi.org/10.1080/17425247.2023.2292692
  11. ACS Mater Au. 2023 Nov 08. 3(6): 620-635
      Cancer is a complex disease with global significance, necessitating continuous advancements in diagnostics and treatment. 3D printing technology has emerged as a revolutionary tool in cancer diagnostics, offering immense potential in detection and monitoring. Traditional diagnostic methods have limitations in providing molecular and genetic tumor information that is crucial for personalized treatment decisions. Biomarkers have become invaluable in cancer diagnostics, but their detection often requires specialized facilities and resources. 3D printing technology enables the fabrication of customized sensor arrays, enhancing the detection of multiple biomarkers specific to different types of cancer. These 3D-printed arrays offer improved sensitivity, allowing the detection of low levels of biomarkers, even in complex samples. Moreover, their specificity can be fine-tuned, reducing false-positive and false-negative results. The streamlined and cost-effective fabrication process of 3D printing makes these sensor arrays accessible, potentially improving cancer diagnostics on a global scale. By harnessing 3D printing, researchers and clinicians can enhance early detection, monitor treatment response, and improve patient outcomes. The integration of 3D printing in cancer diagnostics holds significant promise for the future of personalized cancer care.
    DOI:  https://doi.org/10.1021/acsmaterialsau.3c00046
  12. J Mater Chem B. 2023 Dec 12.
      3D printed/bioprinted tissue constructs are utilized for the regeneration of damaged tissues and as in vitro models. Most of the fabricated 3D constructs fail to undergo functional maturation in conventional in vitro settings. There is a challenge to provide a suitable niche for the fabricated tissue constructs to undergo functional maturation. Bioreactors have emerged as a promising tool to enhance tissue maturation of the engineered constructs by providing physical/biological cues along with a controlled nutrient supply under dynamic in vitro conditions. Bioreactors provide an ambient microenvironment most appropriate for the development of functionally matured tissue constructs by promoting cell proliferation, differentiation, and maturation for transplantation and drug screening applications. Due to the huge cost and limited availability of commercial bioreactors, there is a need to develop strategies to make customized bioreactors. Additive manufacturing (AM) may be a viable tool to fabricate custom designed bioreactors with better efficiency and at low cost. In this review, we have extensively discussed the importance of bioreactors in functionalizing tissue engineered/3D bioprinted scaffolds for bone, cartilage, skeletal muscle, nerve, and vascular tissue. In addition, the importance and fabrication of customized 3D printed bioreactors for the maturation of tissue engineered constructs are discussed in detail. Finally, the current challenges and future perspectives in translating commercial and custom 3D printed bioreactors for clinical applications are outlined.
    DOI:  https://doi.org/10.1039/d3tb01847d
  13. Int J Mol Sci. 2023 Nov 25. pii: 16754. [Epub ahead of print]24(23):
      Current clinical treatment of periodontitis alleviates periodontal symptoms and helps to keep the disease under control for extended periods. Despite this, a significant destruction of the tooth's underlying bone tissue often takes place progressively. Herein, we present a two-way therapeutic approach for local delivery of antibacterial agents and bone tissue regeneration, incorporating ~1% w/w tetracycline hydrochloride (TCH) into a 3D-printed scaffold composed of poly(ε-caprolactone) (PCL). Samples were assessed for their morphological, physicochemical, pharmacokinetic, and antibacterial properties. Furthermore, osteoprecursor cells (MC3T3-E1) were employed to evaluate the osteoinductive potential of the drug-loaded scaffolds. Cell proliferation, viability, and differentiation were determined on all cell-seeded scaffolds. At the end of the culture, PCL-TCH scaffolds promoted abundant collagen organic matrix, demonstrating augmented alkaline phosphatase (ALP) activity and areas of accumulated mineralised bone tissue, despite their belayed cell proliferation. Based on the observed effectiveness of the PCL-TCH scaffolds to inhibit Staphylococcus aureus, these constructs could serve as an alternative bioactive implant that supports bacterial inhibition and favours a 3D microenvironment for bone tissue regeneration in severe periodontitis.
    Keywords:  3D-printed scaffolds; MC3T3-E1 pre-osteoblasts; alveolar bone; periodontitis; tetracycline hydrochloride
    DOI:  https://doi.org/10.3390/ijms242316754