bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–12–01
ten papers selected by
Seerat Maqsood, University of Teramo



  1. Front Bioeng Biotechnol. 2024 ;12 1483547
       Introduction: Bone tissue engineering (BTE) provides an effective repair solution by implanting osteoblasts or stem cells into biocompatible and biodegradable scaffolds to promote bone regeneration. In recent years, the rapid development of 3D bioprinting has enabled its extensive application in fabricating BTE scaffolds. Based on three-dimensional computer models and specialized "bio-inks," this technology offers new pathways for customizing BTE scaffolds. This study reviews the current status and future prospects of scaffold materials for BTE in 3D bioprinting.
    Methods: This literature review collected recent studies on BTE and 3D bioprinting, analyzing the advantages and limitations of various scaffold materials for 3D printing, including bioceramics, metals, natural polymers, and synthetic polymers. Key characteristics like biocompatibility, mechanical properties, and degradation rates of these materials were systematically compared.
    Results: The study highlights the diverse performances of materials used in BTE scaffolds. Bioceramics exhibit excellent biocompatibility but suffer from brittleness; metals offer high strength but may induce chronic inflammation; natural polymers are biocompatible yet have poor mechanical properties, while synthetic polymers offer strong tunability but may produce acidic by-products during degradation. Additionally, integrating 3D bioprinting with composite materials could enhance scaffold biocompatibility and mechanical properties, presenting viable solutions to current challenges.
    Discussion: This review summarizes recent advances in 3D bioprinting for BTE scaffold applications, exploring the strengths and limitations of various materials and proposing composite material combinations to improve scaffold performance. By optimizing material selection and combinations, 3D bioprinting shows promise for creating customized scaffolds, offering a new technical route for clinical applications of BTE. This research provides a unique perspective and theoretical support for advancing 3D bioprinting technology in bone regeneration, outlining future directions for BTE materials and 3D bioprinting technology development.
    Keywords:  3D bioprinting technology; biodegradable materials; bone regeneration; bone tissue engineering; scaffold fabrication
    DOI:  https://doi.org/10.3389/fbioe.2024.1483547
  2. Bioengineering (Basel). 2024 Nov 07. pii: 1123. [Epub ahead of print]11(11):
      Nasal septal cartilage tissue engineering is a promising and dynamic field with the potential to provide surgical options for patients with complex reconstruction needs and mitigate the risks incurred by other tissue sources. Developments in cell source selection, cell expansion, scaffold creation, and three-dimensional (3D) bioprinting have advanced the field in recent years. The usage of medicinal signaling cells and nasal chondroprogenitor cells can enhance chondrocyte proliferation, stimulate chondrocyte growth, and limit chondrocyte dedifferentiate. New scaffolds combined with recent innovations in 3D bioprinting have allowed for the creation of more durable and customizable constructs. Future developments may increase technical accessibility and manufacturability, and lower costs, to help incorporate these methods into pre-clinical studies and clinical applications of septal cartilage tissue engineering.
    Keywords:  3D printed cartilage; bioink; cartilage scaffolds; cartilage tissue engineering; nasal septal cartilage
    DOI:  https://doi.org/10.3390/bioengineering11111123
  3. Materials (Basel). 2024 Nov 06. pii: 5425. [Epub ahead of print]17(22):
      The lacrimal gland (LG) is vital for ocular health, producing tears that lubricate and protect the eye. Dysfunction of the LG leads to aqueous-deficient dry eye disease (DED), significantly impacting quality of life. Current treatments mainly address symptoms rather than the underlying LG dysfunction, highlighting the need for regenerative therapies. Tissue engineering offers a promising solution, with biomaterials playing crucial roles in scaffolding and supporting cell growth for LG regeneration. This review focuses on recent advances in biomaterials used for tissue engineering of the lacrimal gland. We discuss both natural and synthetic biomaterials that mimic the extracellular matrix and provide structural support for cell proliferation and differentiation. Natural biomaterials, such as Matrigel, decellularized extracellular matrices, chitosan, silk fibroin hydrogels, and human amniotic membrane are evaluated for their biocompatibility and ability to support lacrimal gland cells. Synthetic biomaterials, like polyethersulfone, polyesters, and biodegradable polymers (PLLA and PLGA), are assessed for their mechanical properties and potential to create scaffolds that replicate the complex architecture of the LG. We also explore the integration of growth factors and stem cells with these biomaterials to enhance tissue regeneration. Challenges such as achieving proper vascularization, innervation, and long-term functionality of engineered tissues are discussed. Advances in 3D bioprinting and scaffold fabrication techniques are highlighted as promising avenues to overcome current limitations.
    Keywords:  3D bioprinting; biomaterials; dry eye disease; lacrimal gland; natural and synthetic biomaterials; regenerative medicine; tissue engineering
    DOI:  https://doi.org/10.3390/ma17225425
  4. ACS Biomater Sci Eng. 2024 Nov 26.
      Osteochondral tissue damage is a serious concern, with even minor cartilage damage dramatically increasing an individual's risk of osteoarthritis. Therefore, there is a need for an early intervention for osteochondral tissue regeneration. 3D printing is an exciting method for developing novel scaffolds, especially for creating biological scaffolds for osteochondral tissue engineering. However, many 3D printing techniques rely on creating a lattice structure, which often demonstrates poor cell bridging between filaments due to its large pore size, reducing regenerative speed and capacity. To tackle this issue, a novel biphasic scaffold was developed by a combination of 3D printed poly(ethylene glycol)-terephthalate-poly(butylene-terephthalate) (PEGT/PBT) lattice infilled with a porous silk scaffold (derived from Bombyx mori silk fibroin) to make up a bone phase, which continued to a seamless silk top layer, representing a cartilage phase. Compression testing showed scaffolds had Young's modulus, ultimate compressive strength, and fatigue resistance that would allow for their theoretical survival during implantation and joint articulation without stress-shielding mechanosensitive cells. Fluorescent microscopy showed biphasic scaffolds could support the attachment and spreading of human mesenchymal stem cells from bone marrow (hMSC-BM). These promising results highlight the potential utilization of this novel scaffold for osteochondral tissue regeneration as well as highlighting the potential of infilling silk materials within 3D printed scaffolds to further increase their versatility.
    Keywords:  3D printing; Biphasic scaffold; Cartilage regeneration; Osteochondral; Silk fibroin; Tissue Engineering
    DOI:  https://doi.org/10.1021/acsbiomaterials.4c01865
  5. Gels. 2024 Oct 23. pii: 684. [Epub ahead of print]10(11):
      The present study examines the formulation of a biocompatible hydrogel bioink for 3D bioprinting, integrating poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA) using a double-network approach. These materials were chosen for their synergistic qualities, with PEGDA contributing to mechanical integrity and SA ensuring biocompatibility. Fibroblast cells were included in the bioink and printed with a Reg4Life bioprinter employing micro-extrusion technology. The optimisation of printing parameters included needle size and flow velocities. This led to precise structure development and yielded results with a negligible deviation in printed angles and better control of line widths. The rheological characteristics of the bioink were evaluated, demonstrating appropriate viscosity and shear-thinning behaviour for efficient extrusion. The mechanical characterisation revealed an average compressive modulus of 0.38 MPa, suitable for tissue engineering applications. The printability of the bioink was further confirmed through the evaluations of morphology and diffusion rates, confirming structural integrity. Biocompatibility assessments demonstrated a high cell viability rate of 82.65% following 48 h of incubation, supporting the bioink's suitability for facilitating cell survival. This study introduced a reliable technique for producing tissue-engineered scaffolds that exhibit outstanding mechanical characteristics and cell viability, highlighting the promise of PEGDA-SA hydrogels in bioprinting applications.
    Keywords:  biocompatibility; bioprinting; double network; hydrogels; tissue engineering
    DOI:  https://doi.org/10.3390/gels10110684
  6. Adv Funct Mater. 2024 Aug 08. pii: 2315040. [Epub ahead of print]34(32):
      Three-dimensional (3D) bioprinting using photocrosslinkable hydrogels has gained considerable attention due to its versatility in various applications, including tissue engineering and drug delivery. Egg White (EW) is an organic biomaterial with excellent potential in tissue engineering. It provides abundant proteins, along with biocompatibility, bioactivity, adjustable mechanical properties, and intrinsic antiviral and antibacterial features. Here, we have developed a photocrosslinkable hydrogel derived from EW through methacryloyl modification, resulting in Egg White methacryloyl (EWMA). Upon exposure to UV light, synthesized EWMA becomes crosslinked, creating hydrogels with remarkable bioactivity. These hydrogels offer adjustable mechanical and physical properties compatible with most current bioprinters. The EWMA hydrogels closely resemble the native extracellular matrix (ECM) due to cell-binding and matrix metalloproteinase-responsive motifs inherent in EW. In addition, EWMA promotes cell growth and proliferation in 3D cultures. It facilitates vascularization when investigated with human umbilical vein endothelial cells (HUVECs), making it an attractive replacement for engineering hemocompatible vascular grafts and biomedical implants. In summary, the EWMA matrix enables the biofabrication of various living constructs. This breakthrough enhances the development of physiologically relevant 3D in vitro models and opens many opportunities in regenerative medicine.
    Keywords:  3D Bioprinting; Bioink; Egg white; Endothelialization; Hydrogels; Methacryloyl; Photocrosslinking
    DOI:  https://doi.org/10.1002/adfm.202315040
  7. Zhongguo Gu Shang. 2024 Nov 25. 37(11): 1126-31
      Tendon injuries are frequently encountered in clinical practice, and traditional repair methods rarely achieve complete restoration of the tendon's original structure and functionality. The challenges of accelerating and optimizing the healing of injured tendons, enhancing the strength of the regenerated tendon, and preventing adhesion remain significant in clinical settings. Tendon tissue engineering, which combines material science, cell biology, and molecular biology, involves the synergistic application of multiple factors to create functional constructs and has become an emerging technique with promise for repair. The maximization of the regenerative potential of these elements is a critical research question. Future research should concentrate on discovering the optimal combinations of cells, biosignals, and scaffolds to produce tissue that emulates the characteristics of an undamaged, natural tendon. This review will cover various aspects, including the fabrication of tendon tissue scaffolds, the selection of seed cells, strategies for the modulation of healing-related biosignals, and provide a summary with prospective insights, aiming to enhance the comprehension of tissue engineering techniques in tendon injury repair and to inspire innovative applications in this domain.
    Keywords:  Biosignals; Injury and repair; Seed cells; Tendon; Tissue engineering scaffold
    DOI:  https://doi.org/10.12200/j.issn.1003-0034.20240545
  8. Biomimetics (Basel). 2024 Nov 16. pii: 703. [Epub ahead of print]9(11):
      Three-dimensional (3D) printing is a highly effective scaffold manufacturing technique that may revolutionize tissue engineering and regenerative medicine. The use of scaffolds, along with growth factors and cells, remains among the most promising approaches to organ regeneration. However, the applications of hard 3D-printed scaffolds may be limited by their poor surface properties, which play a crucial role in cell recruitment and infiltration, tissue-scaffold integration, and anti-inflammatory properties. However, various prerequisites must be met before 3D-printed scaffolds can be applied clinically to the human body. Consequently, various attempts have been made to modify the surfaces, porosities, and mechanical properties of these scaffolds. Techniques that involve the chemical and material modification of surfaces can also be applied to enhance scaffold efficacy. This review summarizes the characteristics and discusses the developmental directions of the latest 3D-printing technologies according to its intended application in unmet clinical needs.
    Keywords:  3D printing; biomedical application; surface functionalization
    DOI:  https://doi.org/10.3390/biomimetics9110703
  9. Soft Matter. 2024 Nov 29.
      Material extrusion-based three-dimensional (3D) printing is a widely used manufacturing technology for fabricating scaffolds and devices in bone tissue engineering (BTE). This technique involves two fundamentally different extrusion approaches: solution-based and melt-based printing. In solution-based printing, a polymer solution is extruded and solidifies via solvent evaporation, whereas in melt-based printing, the polymer is melted at elevated temperatures and solidifies as it cools post-extrusion. Solution-based printing can also be enhanced to generate micro/nano-scale porosity through phase separation by printing the solution into a nonsolvent bath. The choice of the printing method directly affects scaffold properties and the biological response of stem cells. In this study, we selected polycaprolactone (PCL), a biodegradable polymer frequently used in BTE, blended with hydroxyapatite (HA) nanoparticles, a bioceramic known for promoting bone formation, to investigate the effects of the printing approach on scaffold properties and performance in vitro using human mesenchymal stem cells (hMSCs). Our results showed that while both printing methods produced scaffolds with similar strut and overall scaffold dimensions, solvent-based printing resulted in porous struts, higher surface roughness, lower stiffness, and increased crystallinity compared to melt-based printing. Although stem cell viability and proliferation were not significantly influenced by the printing approach, melt-printed scaffolds promoted a more spread morphology and exhibited pronounced vinculin staining. Furthermore, composite scaffolds outperformed their neat counterparts, with melt-printed composite scaffolds significantly enhancing bone formation. This study highlights the critical role of the printing process in determining scaffold properties and performance, providing valuable insights for optimizing scaffold design in BTE.
    DOI:  https://doi.org/10.1039/d4sm01197j
  10. Nanomicro Lett. 2024 Nov 27. 17(1): 75
      The intricate hierarchical structure of musculoskeletal tissues, including bone and interface tissues, necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes. This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes. Building on the anatomical characteristics of bone and interfacial tissues, this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues, specifically focusing on methods used to construct compositional and structural gradients within the scaffolds. The latest applications of gradient scaffolds for the regeneration of bone, osteochondral, and tendon-to-bone interfaces are presented. Furthermore, the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed, as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.
    Keywords:  Advanced manufacturing; Biomaterials; Gradient scaffolds; Musculoskeletal tissues; Tissue regeneration
    DOI:  https://doi.org/10.1007/s40820-024-01581-4