bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023‒11‒19
twelve papers selected by
Seerat Maqsood, University of Teramo

  1. Nano Converg. 2023 Nov 15. 10(1): 52
      In the field of tissue engineering and regenerative medicine, various hydrogels derived from the extracellular matrix have been utilized for creating engineered tissues and implantable scaffolds. While these hydrogels hold immense promise in the healthcare landscape, conventional bioinks based on ECM hydrogels face several challenges, particularly in terms of lacking the necessary mechanical properties required for 3D bioprinting process. To address these limitations, researchers are actively exploring novel nanomaterial-reinforced ECM hydrogels for both mechanical and functional aspects. In this review, we focused on discussing recent advancements in the fabrication of engineered tissues and monitoring systems using nanobioinks and nanomaterials via 3D bioprinting technology. We highlighted the synergistic benefits of combining numerous nanomaterials into ECM hydrogels and imposing geometrical effects by 3D bioprinting technology. Furthermore, we also elaborated on critical issues remaining at the moment, such as the inhomogeneous dispersion of nanomaterials and consequent technical and practical issues, in the fabrication of complex 3D structures with nanobioinks and nanomaterials. Finally, we elaborated on plausible outlooks for facilitating the use of nanomaterials in biofabrication and advancing the function of engineered tissues.
    Keywords:  3D bioprinting; Engineered tissue; Nanomaterials; Natural ECM hydrogel
  2. Tissue Eng Regen Med. 2023 Nov 18.
      BACKGROUND: Bioglasses are used in applications related to bone rehabilitation and repair. The mechanical and bioactive properties of polysaccharides like alginate and agarose can be modulated or improved using bioglass nanoparticles. Further essential metal ions used as crosslinker have the potential to supplement cultured cells for better growth and proliferation.METHOD: In this study, the alginate bioink is modulated for fabrication of tissue engineering scaffolds by extrusion-based 3D bioprinting using agarose, bioglass nanoparticles and combination of essential trace elements such as iron, zinc, and copper. Homogeneous bioink was obtained by in situ mixing and bioprinting of its components with twin screw extruder (TSE) based 3D bioprinting, and then distribution of metal ions was induced through post-printing diffusion of metal ions in the printed scaffolds. The mechanical and 3d bioprinting properties, microscopic structure, biocompatibility of the crosslinked alginate/agarose hydrogels were analyzed for different concentrations of bioglass. The adipose derived mesenchymal stem cells (ADMSC) and osteoblast cells (MC3T3) were used to evaluate this hydrogel's biological performances.
    RESULTS: The porosity of hydrogels significantly improves with the incorporation of the bioglass. More bioglass concentration results in improved mechanical (compressive, dynamic, and cyclic) and 3D bioprinting properties. Cell growth and extracellular matrix are also enhanced with bioglass concentration.
    CONCLUSION: For bioprinting of the bioinks, the advanced TSE head was attached to 3D bioprinter and in situ fabrication of cell encapsulated scaffold was obtained with optimized composition considering minimal effects on cell damage. Fabricated bioinks demonstrate a biocompatible and noncytotoxic scaffold for culturing MC3T3 and ADMSC, while bioglass controls the cellular behaviors such as cell growth and extracellular matrix formation.
    Keywords:  3D bioprinting bioink; Bioglass; Essential trace metals; Polysaccharide
  3. Mater Today Bio. 2023 Dec;23 100846
      3D bioprinting technology is widely used to fabricate various tissue structures. However, the absence of vessels hampers the ability of bioprinted tissues to receive oxygen and nutrients as well as to remove wastes, leading to a significant reduction in their survival rate. Despite the advancements in bioinks and bioprinting technologies, bioprinted vascular structures continue to be unsuitable for transplantation compared to natural blood vessels. In addition, a complete assessment index system for evaluating the structure and function of bioprinted vessels in vitro has not yet been established. Therefore, in this review, we firstly highlight the significance of selecting suitable bioinks and bioprinting techniques as they two synergize with each other. Subsequently, focusing on both vascular-associated cells and vascular tissues, we provide a relatively thorough assessment of the functions of bioprinted vascular tissue based on the physiological functions that natural blood vessels possess. We end with a review of the applications of vascular models, such as vessel-on-a-chip, in simulating pathological processes and conducting drug screening at the organ level. We believe that the development of fully functional blood vessels will soon make great contributions to tissue engineering and regenerative medicine.
    Keywords:  Assessment of function; Bioink; Bioprinting; Blood vessel; Vascularized structure
  4. AAPS PharmSciTech. 2023 Nov 14. 24(8): 228
      This review explores recent advancements and applications of 3D printing in healthcare, with a focus on personalized medicine, tissue engineering, and medical device production. It also assesses economic, environmental, and ethical considerations. In our review of the literature, we employed a comprehensive search strategy, utilizing well-known databases like PubMed and Google Scholar. Our chosen keywords encompassed essential topics, including 3D printing, personalized medicine, nanotechnology, and related areas. We first screened article titles and abstracts and then conducted a detailed examination of selected articles without imposing any date limitations. The articles selected for inclusion, comprising research studies, clinical investigations, and expert opinions, underwent a meticulous quality assessment. This methodology ensured the incorporation of high-quality sources, contributing to a robust exploration of the role of 3D printing in the realm of healthcare. The review highlights 3D printing's potential in healthcare, including customized drug delivery systems, patient-specific implants, prosthetics, and biofabrication of organs. These innovations have significantly improved patient outcomes. Integration of nanotechnology has enhanced drug delivery precision and biocompatibility. 3D printing also demonstrates cost-effectiveness and sustainability through optimized material usage and recycling. The healthcare sector has witnessed remarkable progress through 3D printing, promoting a patient-centric approach. From personalized implants to radiation shielding and drug delivery systems, 3D printing offers tailored solutions. Its transformative applications, coupled with economic viability and sustainability, have the potential to revolutionize healthcare. Addressing material biocompatibility, standardization, and ethical concerns is essential for responsible adoption.
    Keywords:  3D printing; cost-effectiveness; healthcare innovation; medical devices; nanotechnology; patient perspectives; personalized medicine; sustainability; therapeutic delivery; tissue engineering
  5. Adv Sci (Weinh). 2023 Nov 16. e2304460
      Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient-derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d-bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient-derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient-derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.
    Keywords:  3D bioprinting; cancer model; colorectal cancer; colorectal cancer liver metastases; individualized therapy; precision medicine
  6. ACS Biomater Sci Eng. 2023 Nov 15.
      The controlled delivery of growth factors (GFs) from tissue engineered constructs represents a promising strategy to improve tissue repair and regeneration. However, despite their established key role in tissue regeneration, the use of GFs is limited by their short half-life in the in vivo environment, their dose-dependent effectiveness, and their space- and time-dependent activity. Promising results have been obtained both in vitro and in vivo in animal models. Nevertheless, the clinical application of tissue engineered constructs releasing GFs is still challenging due to the several limitations and risks associated with their use. 3D printing and bioprinting, by allowing the microprecise spatial deposition of multiple materials and the fabrication of complex geometries with high resolution, offer advanced strategies for an optimal release of GFs from tissue engineered constructs. This review summarizes the strategies that have been employed to include GFs and their delivery system into biomaterials used for 3D printing applications to optimize their controlled release and to improve both the in vitro and in vivo regeneration processes. The approaches adopted to overcome the above-mentioned limitations are presented, showing the potential of the technology of 3D printing to get one step closer to clinical applications.
    Keywords:  3D bioprinting; functionalized biomaterial inks; growth factors delivery strategies
  7. Polymers (Basel). 2023 Nov 02. pii: 4306. [Epub ahead of print]15(21):
      In recent years, 3D printing (3DP) has advanced traditional medical treatments. This review explores the fusion of reverse engineering and 3D printing of medical implants, with a specific focus on drug delivery applications. The potential for 3D printing technology to create patient-specific implants and intricate anatomical models is discussed, along with its ability to address challenges in medical treatment. The article summarizes the current landscape, challenges, benefits, and emerging trends of using 3D-printed formulations for medical implantation and drug delivery purposes.
    Keywords:  3D printing; drug delivery; healthcare; implants; medical applications; reverse engineering
  8. Polymers (Basel). 2023 Oct 28. pii: 4250. [Epub ahead of print]15(21):
      The regeneration of bone remains one of the main challenges in the biomedical field, with the need to provide more personalized and multifunctional solutions. The other persistent challenge is related to the local prevention of infections after implantation surgery. To fulfill the first one and provide customized scaffolds with complex geometries, 3D printing is being investigated, with polylactic acid (PLA) as the biomaterial mostly used, given its thermoplastic properties. The 3D printing of PLA in combination with hydroxyapatite (HA) is also under research, to mimic the native mechanical and biological properties, providing more functional scaffolds. Finally, to fulfill the second one, antibacterial drugs locally incorporated into biodegradable scaffolds are also under investigation. This work aims to develop vancomycin-loaded 3D-printed PLA-HA scaffolds offering a dual functionality: local prevention of infections and personalized biodegradable scaffolds with osseointegrative properties. For this, the antibacterial drug vancomycin was incorporated into 3D-printed PLA-HA scaffolds using three loading methodologies: (1) dip coating, (2) drop coating, and (3) direct incorporation in the 3D printing with PLA and HA. A systematic characterization was performed, including release kinetics, Staphylococcus aureus antibacterial/antibiofilm activities and cytocompatibility. The results demonstrated the feasibility of the vancomycin-loaded 3D-printed PLA-HA scaffolds as drug-releasing vehicles with significant antibacterial effects for the three methodologies. In relation to the drug release kinetics, the (1) dip- and (2) drop-coating methodologies achieved burst release (first 60 min) of around 80-90% of the loaded vancomycin, followed by a slower release of the remaining drug for up to 48 h, while the (3) 3D printing presented an extended release beyond 7 days as the polymer degraded. The cytocompatibility of the vancomycin-loaded scaffolds was also confirmed.
    Keywords:  3D printing; antibacterial; biocompatibility; hydroxyapatite; polylactic acid; vancomycin
  9. ACS Appl Mater Interfaces. 2023 Nov 16.
      Loading nanoparticles into hydrogels has been a conventional approach to augment the printability of ink and the physicochemical characteristics of scaffolds in three-dimensional (3D) printing. However, the efficacy of this enhancement has often proven to be limited. We amalgamate electrospun nanofibers with 3D printing techniques to fabricate a composite scaffold reminiscent of a "reinforced concrete" structure, aimed at addressing bone defects. These supple silica nanofibers are synthesized through a dual-step process involving high-speed homogenization and low-temperature ball milling technology. The nanofibers are homogeneously blended with sodium alginate to create the printing ink. The resultant ink was extruded seamlessly, displaying commendable molding properties, thereby yielding scaffolds with favorable macroscopic morphology. In contrast to nanoparticle-reinforced scaffolds, composite scaffolds containing nanofibers exhibit superior mechanical attributes and bioactivity. These nanofiber composite scaffolds demonstrate enhanced osteoinductive properties in both in vitro and in vivo evaluations. To conclude, this research introduces a novel 3D printing approach where the fabricated nanofiber-infused 3D-printed scaffolds hold the potential to revolutionize the realm of 3D printing in the domain of bone tissue engineering.
    Keywords:  3D printing; bone regeneration; nanofibers; scaffold; tissue engineering
  10. J Biomed Mater Res A. 2023 Nov 16.
      Polycaprolactone fumarate (PCLF) is a cross-linkable PCL derivative extensively considered for tissue engineering applications. Although injection molding has been widely used to develop PCLF scaffolds, platforms developed using such technique lack precise control on architecture, design, and porosity required to ensure adequate cellular and tissue responses. In particular, the scaffolds should provide a suitable surface for cell attachment and proliferation, and facilitate cell-cell communication and nutrient flow. 3D printing technologies have led to new architype for biomaterial development with micro-architecture mimicking native tissue. Here, we developed a method for 3D printing of PCLF structures using the extrusion printing technique. The crosslinking property of PCLF enabled the unique post-processing of 3D printed scaffolds resulting in highly porous and flexible PCLF scaffolds with compressive properties imitating natural features of cancellous bone. Generated scaffolds supported excellent attachment and proliferation of mesenchymal stem cells (MSC). The high porosity of PCLF scaffolds facilitated vascularized membrane formation demonstrable with the stringency of the ex ovo chicken chorioallantoic membrane (CAM) implantation. Furthermore, upon implantation to rat calvarium defects, PCLF scaffolds enabled an exceptional new bone formation with a bone mineral density of newly formed bone mirroring native bone tissue. These studies suggest that the 3D-printed highly porous PCLF scaffolds may serve as a suitable biomaterial platform to significantly expand the utility of the PCLF biomaterial for bone tissue engineering applications.
    Keywords:  bone tissue engineering; extrusion printing; polycaprolactone fumarate; porosity
  11. Biomater Res. 2023 Nov 17. 27(1): 117
      BACKGROUND: There is a great clinical need and it remains a challenge to develop artificial soft tissue constructs that can mimic the biomechanical properties and bioactivity of natural tissue. This is partly due to the lack of suitable biomaterials. Hydrogels made from human placenta offer high bioactivity and represent a potential solution to create animal-free 3D bioprinting systems that are both sustainable and acceptable, as placenta is widely considered medical waste. A combination with silk and gelatin polymers can bridge the biomechanical limitations of human placenta chorion extracellular matrix hydrogels (hpcECM) while maintaining their excellent bioactivity.METHOD: In this study, silk fibroin (SF) and tyramine-substituted gelatin (G-TA) were enzymatically crosslinked with human placental extracellular matrix (hpcECM) to produce silk-gelatin-ECM composite hydrogels (SGE) with tunable mechanical properties, preserved elasticity, and bioactive functions. The SGE composite hydrogels were characterized in terms of gelation kinetics, protein folding, and bioactivity. The cyto- and biocompatibility of the SGE composite was determined by in vitro cell culture and subcutaneous implantation in a rat model, respectively. The most cell-supportive SGE formulation was then used for 3-dimensional (3D) bioprinting that induced chemical crosslinking during extrusion.
    CONCLUSION: Addition of G-TA improved the mechanical properties of the SGE composite hydrogels and inhibited crystallization and subsequent stiffening of SF for up to one month. SGE hydrogels exhibit improved and tunable biomechanical properties and high bioactivity for encapsulated cells. In addition, its use as a bioink for 3D bioprinting with free reversible embedding of suspended hydrogels (FRESH) has been validated, opening the possibility to fabricate highly complex scaffolds for artificial soft tissue constructs with natural biomechanics in future.
  12. Int J Reprod Biomed. 2023 Sep;21(9): 681-696
      Male infertility has received vast attention in recent years and has no clear etiology in almost 40% of cases. Several methods have been suggested for preserving sperm and spermatogonial stem cells (SSCs) in both in vivo and in vitro conditions. The efficacy of these methods is related to their abilities, including providing an optimal environment for sperm preservation and long-term SSC culture for in vivo and in vitro differentiation of these cells. In this review article, a full MEDLINE/PubMed search was performed using the following search terms: "Spermatogonial Progenitor Cells, Stem Cells, Fertility Preservations, Sperm Freezing, Cell Differentiations, Tissue Scaffold, 3-Dimensional Cell Culture", which retrieved results from 1973-2022. Related articles were added to the bibliography of selected articles. Exclusion criteria included non-English language, abstract only, and unrelated articles. The production of functioning male germ cells is suggested by introducing modern bioengineered systems as a new hope for the maintenance of male fertility. Till now, few in vitro spermatogenesis investigations have provided appreciable amounts of mature gametes. Each method had benefits and disadvantages, but the 3-dimensional culture method had the greatest impact on the differentiation and preservation of SSCs. One of the critical elements of research is the preservation of sperm and the differentiation of SSCs. Several methods have been employed in this area. Various scaffolds providing an environment similar to an extracellular matrix and conditions for germ cell development and survival have been employed in recent research.
    Keywords:  3D cell culture; Differentiation.; Male infertility; Scaffold; Stem cells; Tissue engineering