bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023‒07‒30
fifteen papers selected by
Seerat Maqsood
University of Teramo

  1. Bioengineering (Basel). 2023 Jul 16. pii: 842. [Epub ahead of print]10(7):
      Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Cardiac tissue engineering is a direction in regenerative medicine that aims to repair various heart defects with the long-term goal of artificially rebuilding a full-scale organ that matches its native structure and function. Three-dimensional (3D) bioprinting offers promising applications through its layer-by-layer biomaterial deposition using different techniques and bio-inks. In this review, we will introduce cardiac tissue engineering, 3D bioprinting processes, bioprinting techniques, bio-ink materials, areas of limitation, and the latest applications of this technology, alongside its future directions for further innovation.
    Keywords:  bio-inks; biomaterials; bioprinting; cardiac tissue engineering
  2. Int J Bioprint. 2023 ;9(5): 748
      Leveraging three-dimensional (3D) bioprinting in the fields of tissue engineering and regenerative medicine has rapidly accelerated progress toward the development of living tissue constructs and biomedical devices. Ongoing vigorous research has pursued the development of 3D in vitro tissue models to replicate the key aspects of human physiology by incorporating relevant cell populations and adequate environmental cues. Given their advantages of being able to intimately mimic the heterogeneity and complexity of their native counterparts, 3D in vitro models hold promise as alternatives to conventional cell cultures or animal models for translational application to model human physiology/pathology and drug screening. Research has highlighted the importance of in vitro models, and a sophisticated biomanufacturing strategy is vitally required. In particular, vascularization is critical for the prolonged survival and functional maturation of the engineered tissues, which has remained one of the major challenges in the establishment of physiologically relevant 3D in vitro models. To this end, 3D bioprinting can efficiently generate solid and reproducible vascularized tissue models with high architectural and compositional similarity to the native tissues, leading to improve the structural maturation and tissue-specific functionality. Multiple bioprinting strategies have been developed to vascularize in vitro tissues by spatially controlled patterning of vascular precursors or generating readily perfusable vascular structures. This review presents an overview of the advanced 3D bioprinting strategies for vascularized tissue model development. We present the key elements for rebuilding functional vasculature in 3D-bioprinted tissue models and discuss the recent achievements in the engineering of 3D vascularized in vitro models using 3D bioprinting. Finally, we delineate the current challenges and future outlooks of 3D bioprinting-based vascularized tissue models.
    Keywords:  3D bioprinting; Biofabrication; In vitro models; Organ-on-a-chip; Vascular tissue models
  3. Bioengineering (Basel). 2023 Jun 30. pii: 787. [Epub ahead of print]10(7):
      To investigate the pathogenic mechanisms of calcified aortic valve disease (CAVD), it is necessary to develop a new three-dimensional model that contains valvular interstitial cells (VIC) and valvular endothelial cells (VEC). For this purpose, ovine aortic valves were processed to isolate VIC and VEC that were dissolved in an alginate/gelatin hydrogel. A 3D-bioprinter (3D-Bioplotter® Developer Series, EnvisionTec, Gladbeck, Germany) was used to print cell-laden tissue constructs containing VIC and VEC which were cultured for up to 21 days. The 3D-architecture, the composition of the culture medium, and the hydrogels were modified, and cell viability was assessed. The composition of the culture medium directly affected the cell viability of the multicellular tissue constructs. Co-culture of VIC and VEC with a mixture of 70% valvular interstitial cell and 30% valvular endothelial cell medium components reached the cell viability best tested with about 60% more living cells compared to pure valvular interstitial cell medium (p = 0.02). The tissue constructs retained comparable cell viability after 21 days (p = 0.90) with different 3D-architectures, including a "sandwich" and a "tube" design. Good long-term cell viability was confirmed even for thick multilayer multicellular tissue constructs. The 3D-bioprinting of multicellular tissue constructs with VEC and VIC is a successful new technique to design tissue constructs that mimic the structure of the native aortic valve for research applications of aortic valve pathologies.
    Keywords:  3D cell culture; 3D printing; bioprinting; calcific aortic valve disease; regenerative medicine; tissue engineering; valvular endothelial cells; valvular interstitial cells
  4. Pharmaceutics. 2023 Jul 04. pii: 1877. [Epub ahead of print]15(7):
      Three-dimensional (3D) printing is an unrivaled technique that uses computer-aided design and programming to create 3D products by stacking materials on a substrate. Today, 3D printing technology is used in the whole drug development process, from preclinical research to clinical trials to frontline medical treatment. From 2009 to 2020, the number of research articles on 3D printing in healthcare applications surged from around 10 to 2000. Three-dimensional printing technology has been applied to several kinds of drug delivery systems, such as oral controlled release systems, micropills, microchips, implants, microneedles, rapid dissolving tablets, and multiphase release dosage forms. Compared with conventional manufacturing methods of pharmaceutical products, 3D printing has many advantages, including high production rates due to the flexible operating systems and high drug loading with the desired precision and accuracy for potent drugs administered in small doses. The cost of production via 3D printing can be decreased by reducing material wastage, and the process can be adapted to multiple classes of pharmaceutically active ingredients, including those with poor solubility. Although several studies have addressed the benefits of 3D printing technology, hospitals and pharmacies have only implemented this process for a small number of practical applications. This article discusses recent 3D printing applications in hospitals and pharmacies for medicinal preparation. The article also covers the potential future applications of 3D printing in pharmaceuticals.
    Keywords:  3D printing; additive manufacturing; personalized medicine; telepharmacy
  5. J Tissue Eng. 2023 Jan-Dec;14:14 20417314231187956
      The repair of growth plate injuries is a highly complex process that involves precise spatiotemporal regulation of multiple cell types. While significant progress has been made in understanding the pathological mechanisms underlying growth plate injuries, effectively regulating this process to regenerate the injured growth plate cartilage remains a challenge. Tissue engineering technology has emerged as a promising therapeutic approach for achieving tissue regeneration through the use of functional biological materials, seed cells and biological factors, and it is now widely applied to the regeneration of bone and cartilage. However, due to the unique structure and function of growth plate cartilage, distinct strategies are required for effective regeneration. Thus, this review provides an overview of current research on the application of tissue engineering to promote growth plate regeneration. It aims to elucidates the underlying mechanisms by which tissue engineering promotes growth plate regeneration and to provide novel insights and therapeutic strategies for future research on the regeneration of growth plate.
    Keywords:  Biomaterials; growth plate injury; regeneration; tissue engineering
  6. Biomater Sci. 2023 Jul 25.
      Designing functional, vascularized, human scale in vitro models with biomimetic architectures and multiple cell types is a highly promising strategy for both a better understanding of natural tissue/organ development stages to inspire regenerative medicine, and to test novel therapeutics on personalized microphysiological systems. Extrusion-based 3D bioprinting is an effective biofabrication technology to engineer living constructs with predefined geometries and cell patterns. However, bioprinting high-resolution multilayered structures with mechanically weak hydrogel bioinks is challenging. The advent of embedded 3D bioprinting systems in recent years offered new avenues to explore this technology for in vitro modeling. By providing a stable, cell-friendly and perfusable environment to hold the bioink during and after printing, it allows to recapitulate native tissues' architecture and function in a well-controlled manner. Besides enabling freeform bioprinting of constructs with complex spatial organization, support baths can further provide functional housing systems for their long-term in vitro maintenance and screening. This minireview summarizes the recent advances in this field and discuss the enormous potential of embedded 3D bioprinting technologies as alternatives for the automated fabrication of more biomimetic in vitro models.
  7. Bioengineering (Basel). 2023 Jun 25. pii: 759. [Epub ahead of print]10(7):
      Immobilization using external or internal splints is a standard and effective procedure to treat minor skeletal fractures. In the case of major skeletal defects caused by extreme trauma, infectious diseases or tumors, the surgical implantation of a bone graft from external sources is required for a complete cure. Practical disadvantages, such as the risk of immune rejection and infection at the implant site, are high in xenografts and allografts. Currently, an autograft from the iliac crest of a patient is considered the "gold standard" method for treating large-scale skeletal defects. However, this method is not an ideal solution due to its limited availability and significant reports of morbidity in the harvest site (30%) as well as the implanted site (5-35%). Tissue-engineered bone grafts aim to create a mechanically strong, biologically viable and degradable bone graft by combining a three-dimensional porous scaffold with osteoblast or progenitor cells. The materials used for such tissue-engineered bone grafts can be broadly divided into ceramic materials (calcium phosphates) and biocompatible/bioactive synthetic polymers. This review summarizes the types of materials used to make scaffolds for cryo-preservable tissue-engineered bone grafts as well as the distinct methods adopted to create the scaffolds, including traditional scaffold fabrication methods (solvent-casting, gas-foaming, electrospinning, thermally induced phase separation) and more recent fabrication methods (fused deposition molding, stereolithography, selective laser sintering, Inkjet 3D printing, laser-assisted bioprinting and 3D bioprinting). This is followed by a short summation of the current osteochondrogenic models along with the required scaffold mechanical properties for in vivo applications. We then present a few results of the effects of freezing and thawing on the structural and mechanical integrity of PLLA scaffolds prepared by the thermally induced phase separation method and conclude this review article by summarizing the current regulatory requirements for tissue-engineered products.
    Keywords:  3D bioprinting; allograft; autograft; bone grafts; calcium phosphates; compressive strength/modulus; freezing; human mesenchymal stem cells (hMSCs); mechanical properties; osteoblasts; porosity; regulatory issues; tissue engineering; xenograft
  8. Pharmaceutics. 2023 Jun 27. pii: 1836. [Epub ahead of print]15(7):
      Cryogels, composed of synthetic and natural materials, have emerged as versatile biomaterials with applications in tissue engineering, controlled drug delivery, regenerative medicine, and therapeutics. However, optimizing cryogel properties, such as mechanical strength and release profiles, remains challenging. To advance the field, researchers are exploring advanced manufacturing techniques, biomimetic design, and addressing long-term stability. Combination therapies and drug delivery systems using cryogels show promise. In vivo evaluation and clinical trials are crucial for safety and efficacy. Overcoming practical challenges, including scalability, structural integrity, mass transfer constraints, biocompatibility, seamless integration, and cost-effectiveness, is essential. By addressing these challenges, cryogels can transform biomedical applications with innovative biomaterials.
    Keywords:  biomaterials; biomedical applications; cryogels; drug delivery; tissue engineering
  9. Regen Biomater. 2023 ;10 rbad060
      Human lifespan continues to extend as an unprecedented number of people reach their seventh and eighth decades of life, unveiling chronic conditions that affect the older adult. Age-related skin conditions include senile purpura, seborrheic keratoses, pemphigus vulgaris, bullous pemphigoid, diabetic foot wounds and skin cancer. Current methods of drug testing prior to clinical trials require the use of pre-clinical animal models, which are often unable to adequately replicate human skin response. Therefore, a reliable model for aged human skin is needed. The current challenges in developing an aged human skin model include the intrinsic variability in skin architecture from person to person. An ideal skin model would incorporate innate functionality such as sensation, vascularization and regeneration. The advent of 3D bioprinting allows us to create human skin equivalent for use as clinical-grade surgical graft, for drug testing and other needs. In this review, we describe the process of human skin aging and outline the steps to create an aged skin model with 3D bioprinting using skin cells (i.e. keratinocytes, fibroblasts and melanocytes). We also provide an overview of current bioprinted skin models, associated limitations and direction for future research.
    Keywords:  3D bioprinting; aging; bioink; regeneration; skin
  10. Biomolecules. 2023 Jun 30. pii: 1062. [Epub ahead of print]13(7):
      Hydrogels have been widely applied to the fabrication of tissue engineering scaffolds via three-dimensional (3D) bioprinting because of their extracellular matrix-like properties, capacity for living cell encapsulation, and shapeable customization depending on the defect shape. However, the current hydrogel scaffolds show limited regeneration activity, especially in the application of periodontal tissue regeneration. In this study, we attempted to develop a novel multi-component hydrogel that possesses good biological activity, can wrap living cells for 3D bioprinting and can regenerate periodontal soft and hard tissue. The multi-component hydrogel consisted of gelatin methacryloyl (GelMA), sodium alginate (SA) and bioactive glass microsphere (BGM), which was first processed into hydrogel scaffolds by cell-free 3D printing to evaluate its printability and in vitro biological performances. The cell-free 3D-printed scaffolds showed uniform porous structures and good swelling capability. The BGM-loaded scaffold exhibited good biocompatibility, enhanced osteogenic differentiation, apatite formation abilities and desired mechanical strength. The composite hydrogel was further applied as a bio-ink to load with mouse bone marrow mesenchymal stem cells (mBMSCs) and growth factors (BMP2 and PDGF) for the fabrication of a scaffold for periodontal tissue regeneration. The cell wrapped in the hydrogel still maintained good cellular vitality after 3D bioprinting and showed enhanced osteogenic differentiation and soft tissue repair capabilities in BMP2- and PDGF-loaded scaffolds. It was noted that after transplantation of the cell- and growth factor-laden scaffolds in Beagle dog periodontal defects, significant regeneration of gingival tissue, periodontal ligament, and alveolar bone was detected. Importantly, a reconstructed periodontal structure was established in the treatment group eight weeks post-transplantation of the scaffolds containing the cell and growth factors. In conclusion, we developed a bioactive composite bio-ink for the fabrication of scaffolds applicable for the reconstruction and regeneration of periodontal tissue defects.
    Keywords:  3D bioprinting; cell-laden scaffold; composite hydrogel; periodontal regeneration
  11. Heliyon. 2023 Jul;9(7): e17050
      Repairing significant bone defects remains a critical challenge, raising the clinical demand to design novel bone biomaterials that incorporate osteogenic and angiogenic properties to support the regeneration of vascularized bone. Bioactive glass scaffolds can stimulate angiogenesis and osteogenesis. In addition, natural or synthetic polymers exhibit structural similarity with extracellular matrix (ECM) components and have superior biocompatibility and biodegradability. Thus, there is a need to prepare composite scaffolds of hydrogels for vascularized bone, which incorporate to improve the mechanical properties and bioactivity of natural polymers. In addition, those composites' 3-dimensional (3D) form offer regenerative benefits such as direct doping of the scaffold with ions. This review presents a comprehensive discussion of composite scaffolds incorporated with BaG, focusing on their effects on osteo-inductivity and angiogenic properties. Moreover, the adaptation of the ion-doped hydrogel composite scaffold into a 3D scaffold for the generation of vascularized bone tissue is exposed. Finally, we highlight the challenges and future of manufacturing such biomaterials.
    Keywords:  3D scaffold; Bioactive glasses; Ion-doped hydrogel scaffold; Vascularized bone
  12. Materials (Basel). 2023 Jul 10. pii: 4923. [Epub ahead of print]16(14):
      Polymers in the form of films, fibers, nano- and microspheres, composites, and porous supports are promising biomaterials for a wide range of advanced biomedical applications: wound healing, controlling drug delivery, anti-cancer therapy, biosensors, stem cell therapy, and tissue engineering [...].
  13. Polymers (Basel). 2023 Jul 21. pii: 3103. [Epub ahead of print]15(14):
      In recent years, the biomedical engineering field has seen remarkable advancements, focusing mainly on developing novel solutions for enhancing tissue regeneration or improving therapeutic outcomes [...].
  14. Int J Biol Macromol. 2023 Jul 25. pii: S0141-8130(23)02886-6. [Epub ahead of print] 125991
      Novel electrically conductive nanofibrous scaffolds were designed and fabricated through the grafting of aniline monomer onto a phenylamine-functionalized alginate (Alg-NH2) followed by electrospinning with poly(vinyl alcohol) (PVA). Performance of the prepared scaffolds in bone tissue engineering (TE) were studied in terms of physicochemical (e.g., conductivity, electroactivity, morphology, hydrophilicity, water uptake, and mechanical) and biological (cytocompatibility, in vitro biodegradability, cells attachment and proliferation, hemolysis, and protein adsorption) properties. The contact angles of the scaffolds with water drop were obtained about 50 to 60° that confirmed their excellent hydrophilicities for TE applications. Three dimensional (3D), inter-connected and uniform porous structures of the scaffolds without any bead formation was confirmed by scanning electron microscopy (SEM). Electrical conductivities of the fabricated scaffolds were obtained as 1.5 × 10-3 and 2.7 × 10-3 Scm-1. MTT assay results revealed that the scaffolds have acceptable cytocompatibilities and can enhance the cells adhesion as well as proliferation, which approved their potential for TE applications. Hemolysis rate of developed scaffolds were quantified <2 % even at high concentration (200 μgmL-1) of samples that approved their hemocompatibilities. The scaffolds were also exhibited acceptable protein adsorption capacities (65 and 68 μgmg-1). As numerous experimental results, the developed scaffolds have acceptable potential for bone TE.
    Keywords:  Alginate; Polyaniline; Tissue engineering
  15. J Funct Biomater. 2023 Jun 29. pii: 347. [Epub ahead of print]14(7):
      4D printing has emerged as a transformative technology in the field of biomedical engineering, offering the potential for dynamic, stimuli-responsive structures with applications in tissue engineering, drug delivery, medical devices, and diagnostics. This review paper provides a comprehensive analysis of the advancements, challenges, and future directions of 4D printing in biomedical engineering. We discuss the development of smart materials, including stimuli-responsive polymers, shape-memory materials, and bio-inks, as well as the various fabrication techniques employed, such as direct-write assembly, stereolithography, and multi-material jetting. Despite the promising advances, several challenges persist, including material limitations related to biocompatibility, mechanical properties, and degradation rates; fabrication complexities arising from the integration of multiple materials, resolution and accuracy, and scalability; and regulatory and ethical considerations surrounding safety and efficacy. As we explore the future directions for 4D printing, we emphasise the need for material innovations, fabrication advancements, and emerging applications such as personalised medicine, nanomedicine, and bioelectronic devices. Interdisciplinary research and collaboration between material science, biology, engineering, regulatory agencies, and industry are essential for overcoming challenges and realising the full potential of 4D printing in the biomedical engineering landscape.
    Keywords:  4D printing; biocompatibility; biomedical engineering; fabrication techniques; smart materials