bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024–07–07
nine papers selected by
Seerat Maqsood, University of Teramo



  1. Trends Biotechnol. 2024 Jul 01. pii: S0167-7799(24)00145-8. [Epub ahead of print]
      3D printing has revolutionized bone tissue engineering (BTE) by enabling the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration. The superior biocompatibility, customizable bioactivity, and biodegradability have enabled calcium phosphate (CaP) to gain significance as a bone graft material. 3D-printed (3DP) CaP scaffolds allow precise drug delivery due to their porous structure, adaptable structure-property relationship, dynamic chemistry, and controlled dissolution. The effectiveness of conventional scaffold-based drug delivery is hampered by initial burst release and drug loss. This review summarizes different multifunctional drug delivery approaches explored in controlling drug release, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion printing for BTE applications. The review also outlines perspectives and future challenges in drug delivery research, paving the way for next-generation bone repair methodologies.
    Keywords:  3D printing; calcium phosphate scaffold; controlled release; drug delivery
    DOI:  https://doi.org/10.1016/j.tibtech.2024.05.006
  2. Tissue Eng Part C Methods. 2024 Jul 01.
      In the advent of tissue engineering and regenerative medicine, the demand for innovative approaches to biofabricate complex vascular structures is increasing. We describe a single-step 3D bioprinting method leveraging Aspect Biosystems RX1 technology, that integrates the crosslinking step at a flow-focusing junction, to biofabricate immortalized adult rat brain endothelial cell (SV-ARBEC)-encapsulated in alginate-collagen type I hydrogel rings, enabling robust angiogenesis and the formation of intricate vascular-like networks. This single-step biofabrication process involves the strategic layer-by-layer assembly of hydrogel rings, encapsulating SV-ARBECs in a spatially controlled manner while optimizing access to media and nutrients. The spatial arrangement of endothelial cells within the rings promotes angiogenic network formation and the organized development of vascular-like networks through facilitated constrained deposition of the cells within the hydrogel matrix forming tissue-like structures. This approach provides a platform that can be adapted to many different endothelial cell types and leveraged to better understanding the mechanisms driving angiogenesis and vascular-network formation in 3D bioprinted constructs supporting the development of more complex tissue and disease models for advancing drug discovery, tissue engineering and regenerative applications.
    DOI:  https://doi.org/10.1089/ten.TEC.2024.0083
  3. Colloids Surf B Biointerfaces. 2024 Jun 26. pii: S0927-7765(24)00323-0. [Epub ahead of print]241 114064
      Bile duct injury presents a significant clinical challenge following hepatobiliary surgery, necessitating advancements in the repair of damaged bile ducts is a persistent issue in biliary surgery. 3D printed tubular scaffolds have emerged as a promising approach for the repair of ductal tissues, yet the development of scaffolds that balance exceptional mechanical properties with biocompatibility remains an ongoing challenge. This study introduces a novel, bio-fabricated bilayer bile duct scaffold using a 3D printing technique. The scaffold comprises an inner layer of polyethylene glycol diacrylate (PEGDA) to provide high mechanical strength, and an outer layer of biocompatible, methacryloylated recombinant collagen type III (rColMA) loaded with basic fibroblast growth factor (bFGF)-encapsulated liposomes (bFGF@Lip). This design enables the controlled release of bFGF, creating an optimal environment for the growth and differentiation of bone marrow mesenchymal stem cells (BMSCs) into cholangiocyte-like cells. These cells are instrumental in the regeneration of bile duct tissues, evidenced by the pronounced expression of cholangiocyte differentiation markers CK19 and CFTR. The PEGDA//rColMA/bFGF@Lip bilayer bile duct scaffold can well simulate the bile duct structure, and the outer rColMA/bFGF@Lip hydrogel can well promote the growth and differentiation of BMSCs into bile duct epithelial cells. In vivo experiments showed that the scaffold did not cause cholestasis in the body. This new in vitro pre-differentiated active 3D printed scaffold provides new ideas for the study of bile duct tissue replacement.
    Keywords:  3D printing; Bilayer scaffolds; Bile duct repair; Hydrogel; Methacryloylated recombinant type III collagen (rColMA); Polyethylene glycol diacrylate (PEGDA)
    DOI:  https://doi.org/10.1016/j.colsurfb.2024.114064
  4. Clin Transl Sci. 2024 Jul;17(7): e13863
      Ovaries play a crucial role in the regulation of numerous essential processes that occur within the intricate framework of female physiology. They are entrusted with the responsibility of both generating a new life and orchestrating a delicate hormonal symphony. Understanding their functioning is crucial for gaining insight into the complexities of reproduction, health, and fertility. In addition, ovaries secrete hormones that are crucial for both secondary sexual characteristics and the maintenance of overall health. A three-dimensional (3D) prosthetic ovary has the potential to restore ovarian function and preserve fertility in younger females who have undergone ovariectomies or are afflicted with ovarian malfunction. Clinical studies have not yet commenced, and the production of 3D ovarian tissue for human implantation is still in the research phase. The main challenges faced while creating a 3D ovary for in vivo implantation include sustenance of ovarian follicles, achieving vascular infiltration into the host tissue, and restoring hormone circulation. The complex ovarian microenvironment that is compartmentalized and rigid makes the biomimicking of the 3D ovary challenging in terms of biomaterial selection and bioink composition. The successful restoration of these properties in animal models has led to expectations for the development of human ovaries for implantation. This review article summarizes and evaluates the optimal 3D models of ovarian structures and their safety and efficacy concerns to provide concrete suggestions for future research.
    DOI:  https://doi.org/10.1111/cts.13863
  5. Biofabrication. 2024 Jul 05.
      Three-dimensional (3D) printing is an emerging tool for creating patient-specific tissue constructs analogous to the native tissue microarchitecture. In this study, anatomically equivalent 3D nerve conduits were developed using thermoplastic polyurethane (TPU) by combining reverse engineering and material extrusion (i.e., fused deposition modeling) technique. Printing parameters were optimized to fabricate nerve-equivalent TPU constructs. The TPU constructs printed with different infill densities supported the adhesion, proliferation, and gene expression of neuronal cells. Subcutaneous implantation of the TPU constructs for three months in rats showed neovascularization with negligible local tissue inflammatory reactions and was classified as a non-irritant biomaterial as per ISO 10993-6. To perform in vivo efficacy studies, nerve conduits equivalent to rat's sciatic nerve were fabricated and bridged in a 10 mm sciatic nerve transection model. After four months of implantation, the sensorimotor function and histological assessments revealed that the 3D printed TPU conduits promoted the regeneration in critical-sized peripheral nerve defects equivalent to autografts. This study proved that TPU-based 3D printed nerve guidance conduits can be created to replicate the complicated features of natural nerves that can promote the regeneration of peripheral nerve defects and also show the potential to be extended to several other tissues for regenerative medicine applications.&#xD.
    Keywords:  3D printing; Peripheral nerve injuries; Thermoplastic polyurethane; nerve regeneration; reverse engineering
    DOI:  https://doi.org/10.1088/1758-5090/ad5fbe
  6. Food Chem. 2024 Jul 02. pii: S0308-8146(24)01944-7. [Epub ahead of print]458 140294
      Three-dimensional (3D) printing, as an emerging digital production technology, has recently been receiving increasing attention in food processing. It is important to understand the effect of key ingredients of food materials on the printing, which makes it possible to achieve a wider range of structures using few nozzles and to provide tailored nutrition and personalization. This comprehensive review delves into the latest research on 3D-printed lipid-based foods, encompassing a variety of products such as chocolate, processed cheese, as well as meat. It also explores the development and application of food bioinks that incorporate lipids as a pivotal component, including those based on starch, protein, oleogels, bigels, and emulsions, as well as emulsion gels. Moreover, this review identifies the current challenges and presents an outlook on future research directions in the field of 3D food printing, especially the research and application of lipids in food 3D printing.
    Keywords:  3D food printing; Fat; Lipids; Materials; Oil; Printability
    DOI:  https://doi.org/10.1016/j.foodchem.2024.140294
  7. World Neurosurg. 2024 Jun 28. pii: S1878-8750(24)01092-1. [Epub ahead of print]
       OBJECTIVE: To assess the utility of 3D printing positioning technology for resection of parasagittal meningioma.
    METHODS: Information related to clinical history, application of 3D printing positioning technology, neuroimaging, surgical related information and postoperative hospital days of consecutive patients with parasagittal meningioma between January 2020 and December 2022 were retrospectively collected. Patients were divided into two groups based on whether the 3D printing positioning technology was applied. The values between groups were statistically compared.
    RESULTS: A total of 41 patients were enrolled. In cases using 3D printing positioning technology (14 patients), the location of craniotomy was much better and the postoperative hospital stay was much shorter.
    CONCLUSION: The application of 3D printing positioning technology in parasagittal meningioma surgery could improve the location of craniotomy, and reduce the postoperative hospital stay. It is a low-cost positioning technology, and has the potential to be applied to other superficial intracranial tumors.
    Keywords:  3D printing; parasagittal meningioma; positioning technology
    DOI:  https://doi.org/10.1016/j.wneu.2024.06.134
  8. Biomed Eng Lett. 2024 Jul;14(4): 737-746
      Microneedles (MNs) have emerged as an innovative, virtually painless technique for intradermal drug delivery. However, the complex and costly fabrication process has limited their widespread accessibility, especially for individuals requiring frequent drug administration. This study introduces a groundbreaking and cost-effective method for producing MNs utilizing fused deposition modeling (FDM) 3D printing technology to enhance transdermal drug delivery. The proposed fabrication process involves the elongation of molten polylactic acid (PLA) filaments to create meticulously designed conoid and neiloid MNs with smooth surfaces. This study underscores the critical role of printing parameters, particularly extrusion length and printing speed, in determining the shape of the MNs. Notably, the conoid-shaped MNs exhibit exceptional skin-penetrating capabilities. In order to evaluate their effectiveness, the MNs were tested on a polydimethylsiloxane (PDMS) skin model for skin penetration. The results highlight the high potential of 3D-printed MNs for transdermal drug administration. This novel approach capitalizes on the benefits of 3D printing technology to fabricate MNs that hold the promise of transforming painless drug administration for a variety of medical applications.
    Keywords:  FDM 3D printing; Microneedle; Neiloid and conoid shapes; Skin penetration; Transdermal drug delivery
    DOI:  https://doi.org/10.1007/s13534-024-00368-1
  9. ACS Biomater Sci Eng. 2024 Jul 03.
      Hair follicle-penetrating nanoparticles offer a promising avenue for targeted antibiotic delivery, especially in challenging infections like acne inversa or folliculitis decalvans. However, demonstrating their efficacy with existing preclinical models remains difficult. This study presents an innovative approach using a 3D in vitro organ culture system with human hair follicles to investigate the hypothesis that antibiotic nanocarriers may reach bacteria within the follicular cleft more effectively than free drugs. Living human hair follicles were transplanted into a collagen matrix within a 3D printed polymer scaffold to replicate the follicle's microenvironment. Hair growth kinetics over 7 days resembled those of simple floating cultures. In the 3D model, fluorescent nanoparticles exhibited some penetration into the follicle, not observed in floating cultures. Staphylococcus aureus bacteria displayed similar distribution profiles postinfection of follicles. While rifampicin-loaded lipid nanocapsules were as effective as free rifampicin in floating cultures, only nanoencapsulated rifampicin achieved the same reduction of CFU/mL in the 3D model. This underscores the hair follicle microenvironment's critical role in limiting conventional antibiotic treatment efficacy. By mimicking this microenvironment, the 3D model demonstrates the advantage of topically administered nanocarriers for targeted antibiotic therapy against follicular infections.
    Keywords:  3D fabrication; follicular transport; hair follicle infection; in vitro model; tissue engineering
    DOI:  https://doi.org/10.1021/acsbiomaterials.4c00570