bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024‒10‒13
eight papers selected by
Seerat Maqsood, University of Teramo



  1. Tissue Eng Part B Rev. 2024 Oct 09.
      Articular cartilage is crucial in human physiology, and its degeneration poses a significant public health challenge. While recent advancements in 3D bioprinting and tissue engineering show promise for cartilage regeneration, there remains a gap between research findings and clinical application. This review critically examines the mechanical and biological properties of hyaline cartilage, along with current 3D manufacturing methods and analysis techniques. Moreover, we provide a quantitative synthesis of bioink properties used in cartilage tissue engineering. After screening 181 initial works, 33 studies using extrusion bioprinting were analyzed and synthesized, presenting results that indicate the main materials, cells, and methods utilized for mechanical and biological evaluation. Altogether, this review motivates the standardization of mechanical analyses and biomaterial assessments of 3D bioprinted constructs to clarify their chondrogenic potential.
    Keywords:  articular cartilage; biomechanics; bioprinting; hydrogels
    DOI:  https://doi.org/10.1089/ten.teb.2024.0168
  2. EXCLI J. 2024 ;23 1170-1182
      Cartilage tissue, characterized by its limited regenerative capacity, presents significant challenges in clinical therapy. Recent advancements in cartilage regeneration have focused on integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to overcome existing limitations. Stem cells, particularly Mesenchymal Stem Cells (MSCs) and induced pluripotent stem cells (iPSCs), hold promise for cartilage repair due to their ability to differentiate into chondrocytes, the key cells responsible for cartilage formation. Tissue engineering approaches, including 3D models, organ-on-a-chip systems, and organoids, offer innovative methods to mimic natural tissue microenvironments and evaluate potential treatments. MSC-based techniques, such as cell sheet tissue engineering, address challenges associated with traditional therapies, including cell availability and culture difficulties. Furthermore, advancements in 3D bioprinting enable the fabrication of complex tissue structures, while organ-on-a-chip systems provide microfluidic platforms for disease modeling and physiological mimicry. Organoids serve as simplified models of organs, capturing some complexity and enabling the monitoring of pathophysiological aspects of cartilage diseases. This comprehensive review underscores the transformative potential of integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to improve cartilage regeneration and pave the way for more effective clinical treatments.
    Keywords:  3D bioprinting; biomaterials; cartilage regeneration; chondrogenesis; clinical trials; exosomes; extracellular matrix; organ-on-a-chip; stem cells; tissue engineering
    DOI:  https://doi.org/10.17179/excli2024-7088
  3. Int J Biol Macromol. 2024 Oct 09. pii: S0141-8130(24)07193-9. [Epub ahead of print]281(Pt 2): 136384
      Nowadays, bone injuries and disorders have increased all over the world and can reduce the quality of human life. Bone tissue engineering repair approaches require new biomaterials and methods to construct scaffolds with the required structural properties as well as improved performance. As potential therapeutic strategies in bone tissue engineering, 3D printed scaffolds have been developed. Polycaprolactone/Ceramic composites have attracted considerable attention due to their cytocompatibility, biodegradability, and physical properties. In this study, a 3D printing process was used to create polycaprolactone (PCL)-Gelatin (GEL) scaffolds containing varying concentrations of Bioglass (BG) and Nano Montmorillonite (MMT). This mixture was then loaded into a 3D printer, and the scaffolds were printed layer by layer. After constructing the scaffolds, they were then examined for their physical, chemical, and biological characteristics. Surface appearance was analyzed with a scanning electron microscope (SEM), which revealed that NC increased the diameter of pores from 465 to 480 μm. The elements in the scaffolds were evaluated by EDX analysis, and a uniform dispersion of nano montmorillonite particles was observed. The compressive strength reached 76.43 MPa for PCL/G/35 %MMT/15 %BG scaffold. Also, the rate of water absorption, biodegradability and bioactivity of PCL-GEL scaffolds increased significantly in the presence of NC. According to the MTT cell test results, adding BG and NC increased cell proliferation, adhesion and cell viability to 127.7 %. These findings indicated that the 3D printed PCL/G/35 %MMT/15 %BG scaffold has promising strategies for bone repair applications. Also, polynomial curve fitting shows that scaffold degradability after soaking in PBS can be predicted using the initial weight and soaking time. Adding more variables and data could improve prediction accuracy, reducing the need for experiments and conserving resources.
    Keywords:  3D printing; Bioglass; Biomineralization; Bone tissue engineering; Nano montmorillonite; PCL hybrid scaffold
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.136384
  4. Sci Rep. 2024 10 05. 14(1): 23240
      Gelatin methacryloyl (GelMA), typically derived from mammalian sources, has recently emerged as an ideal bio-ink for three-dimensional (3D) bioprinting. Herein, we developed a fish skin-based GelMA bio-ink for the fabrication of a 3D GelMA skin substitute with a 3D bioprinter. Several concentrations of methacrylic acid anhydride were used to fabricate GelMA, in which their physical-mechanical properties were assessed. This fish skin-based GelMA bio-ink was loaded with human adipose tissue-derived mesenchymal stromal cells (ASCs) and human platelet lysate (HPL) and then printed to obtain 3D ASCs + HPL-loaded GelMA scaffolds. Cell viability test and a preliminary investigation of its effectiveness in promoting wound closure were evaluated in a critical-sized full thickness skin defect in a rat model. The cell viability results showed that the number of ASCs increased significantly within the 3D GelMA hydrogel scaffold, indicating its biocompatibility property. In vivo results demonstrated that ASCs + HPL-loaded GelMA scaffolds could delay wound contraction, markedly enhanced collagen deposition, and promoted the formation of new blood vessels, especially at the wound edge, compared to the untreated group. Therefore, this newly fish skin-based GelMA bio-ink developed in this study has the potential to be utilized for the printing of 3D GelMA skin substitutes.
    Keywords:  3D bioprinting; Bio-ink; Critical-sized full thickness skin defect; Fish skin gelatin; GelMA hydrogel; Skin substitute
    DOI:  https://doi.org/10.1038/s41598-024-73774-1
  5. Front Bioeng Biotechnol. 2024 ;12 1385365
      Introduction: 3D-printed scaffolds have emerged as an alternative for addressing the current limitations encountered in bone reconstruction. This study aimed to systematically review the feasibility of using 3D bio-printed scaffolds as a material for bone grafting in animal models, focusing on femoral and tibial defects. The primary objective of this study was to evaluate the efficacy, safety, and overall impact of these scaffolds on bone regeneration.Methods: Electronic databases were searched using specific search terms from January 2013 to October 2023, and 37 relevant studies were finally included and reviewed. We documented the type of scaffold generated using the 3D printed techniques, detailing its characterization and rheological properties including porosity, compressive strength, shrinkage, elastic modulus, and other relevant factors. Before incorporating them into the meta-analysis, an additional inclusion criterion was applied where the regenerated bone area (BA), bone volume (BV), bone volume per total volume (BV/TV), trabecular thickness (Tb. Th.), trabecular number (Tb. N.), and trabecular separation (Tb. S.) were collected and analyzed statistically.
    Results: 3D bio-printed ceramic-based composite scaffolds exhibited the highest capacity for bone tissue regeneration (BTR) regarding BV/TV of femoral and tibial defects of animal models. The ideal structure of the printed scaffolds displayed optimal results with a total porosity >50% with a pore size ranging between 300- and 400 µM. Moreover, integrating additional features and engineered macro-channels within these scaffolds notably enhanced BTR capacity, especially observed at extended time points.
    Discussion: In conclusion, 3D-printed composite scaffolds have shown promise as an alternative for addressing bone defects.
    Keywords:  3D printing; biomaterials; bone defects; bone repair; meta-analysis
    DOI:  https://doi.org/10.3389/fbioe.2024.1385365
  6. Adv Funct Mater. 2024 Jul 10. pii: 2313942. [Epub ahead of print]34(28):
      3-D bioprinting is a promising technology to fabricate custom geometries for tissue engineering. However, most bioprintable hydrogels are weak and fragile, difficult to handle and cannot mimetic the mechanical behaviors of the native soft elastic tissues. We have developed a visible light crosslinked, single-network, elastic and biocompatible hydrogel system based on an acrylated triblock copolymer of poly(ethylene glycol) PEG and polycaprolactone (PCL) (PEG-PCL-DA). To enable its application in bioprinting of soft tissues, we have modified the hydrogel system on its printability and biodegradability. Furthermore, we hypothesize that this elastic material can better transmit pulsatile forces to cells, leading to enhanced cellular response under mechanical stimulation. This central hypothesis was tested using vascular conduits with smooth muscle cells (SMCs) cultured under pulsatile forces in a custom-made bioreactor. The results showed that vascular conduits made of PEG-PCL-DA hydrogel faithfully recapitulate the rapid stretch and recoil under the pulsatile pressure from 1 to 3 Hz frequency, which induced a contractile SMC phenotype, consistently upregulated the core contractile transcription factors. In summary, our work demonstrates the potential of elastic hydrogel for 3D bioprinting of soft tissues by fine tuning the printability, biodegradability, while possess robust elastic property suitable for manual handling and biomechanical stimulation.
    Keywords:  3D bioprinting; elastic hydrogel; mechanical stimulation; smooth muscle cells; soft tissue
    DOI:  https://doi.org/10.1002/adfm.202313942
  7. Bioact Mater. 2025 Jan;43 195-224
      The epithelium is one of the important tissues in the body as it plays a crucial barrier role serving as a gateway into and out of the body. Most organs in the body contain an epithelial tissue component, where the tightly connected, organ-specific epithelial cells organize into cysts, invaginations, or tubules, thereby performing distinct to endocrine or exocrine secretory functions. Despite the significance of epithelium, engineering functional epithelium in vitro has remained a challenge due to it is special architecture, heterotypic composition of epithelial tissues, and most importantly, difficulty in attaining the apico-basal and planar polarity of epithelial cells. Bioprinting has brought a paradigm shift in fabricating such apico-basal polarized tissues. In this review, we provide an overview of epithelial tissues and provide insights on recapitulating their cellular arrangement and polarization to achieve epithelial function. We describe the different bioprinting techniques that have been successful in engineering polarized epithelium, which can serve as in vitro models for understanding homeostasis and studying diseased conditions. We also discuss the different attempts that have been investigated to study these 3D bioprinted engineered epithelium for preclinical use. Finally, we highlight the challenges and the opportunities that need to be addressed for translation of 3D bioprinted epithelial tissues towards paving way for personalized healthcare in the future.
    Keywords:  3D bioprinting; 3D in vitro models; Engineered epithelium; In vitro disease modeling
    DOI:  https://doi.org/10.1016/j.bioactmat.2024.09.025
  8. J Mater Sci Mater Med. 2024 Oct 07. 35(1): 62
      Prolonged osteochondral tissue engineering damage can result in osteoarthritis and decreased quality of life. Multiphasic scaffolds, where different layers model different microenvironments, are a promising treatment approach, yet stable joining between layers during fabrication remains challenging. To overcome this problem, in this study, a bilayer scaffold for osteochondral tissue regeneration was fabricated using 3D printing technology which containing a layer of PCL/hydroxyapatite (HA) nanoparticles and another layer of PCL/gelatin with various concentrations of fibrin (10, 20 and 30 wt.%). These printed scaffolds were evaluated with SEM (Scanning Electron Microscopy), FTIR (Fourier Transform Infrared Spectroscopy) and mechanical properties. The results showed that the porous scaffolds fabricated with pore size of 210-255 µm. Following, the ductility increased with the further addition of fibrin in bilayer composites which showed these composites scaffolds are suitable for the cartilage part of osteochondral. Also, the contact angle results demonstrated the incorporation of fibrin in bilayer scaffolds based on PCL matrix, can lead to a decrease in contact angle and result in the improvement of hydrophilicity that confirmed by increasing the degradation rate of scaffolds containing further fibrin percentage. The bioactivity study of bilayer scaffolds indicated that both fibrin and hydroxyapatite can significantly improve the cell attachment on fabricated scaffolds. The MTT assay, DAPI and Alizarin red tests of bilayer composite scaffolds showed that samples containing 30% fibrin have the more biocompatibility than that of samples with 10 and 20% fibrin which indicated the potential of this bilayer scaffold for osteochondral tissue regeneration.
    DOI:  https://doi.org/10.1007/s10856-024-06824-9