bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2023‒06‒11
fifteen papers selected by
Seerat Maqsood
University of Teramo

  1. J Law Med. 2023 May;30(1): 85-98
      This article discusses ownership and property issues in three-dimensional (3D) bioprinting from the perspective of the tangible aspect of the technology. Many scholars have examined property issues in the intangible aspect of the technology, namely, the intellectual property issue. Since a major component of 3D bioprinting is cells taken from patients and donors, it is important to explore the right of ownership over the physical product, including cells used in the 3D bioprinting process and the 3D bioprinted organ itself. What is the extent of the donor's right over his/her cells taken for use in 3D bioprinting and even the 3D bioprinted organ - the product of those cells? For example, can the cell donor determine how his/her cells are used, or even who gets the 3D bioprinted organ? What rights does a person have over the commercial use of his/her cells or tissue for 3D bioprinting?
    Keywords:  3D bioprinting; CAD files; Moore; biomaterials; conversion; organ manufacturing; ownership; property issue
  2. Int J Bioprint. 2023 ;9(3): 714
      The absolute shortage of compatible liver donors and the growing number of potential recipients have led scientists to explore alternative approaches to providing tissue/ organ substitutes from bioengineered sources. Bioartificial regeneration of a fully functional tissue/organ replacement is highly dependent on the right combination of engineering tools, biological principles, and materiobiology horizons. Over the past two decades, remarkable achievements have been made in hepatic tissue engineering by converging various advanced interdisciplinary research approaches. Three-dimensional (3D) bioprinting has arisen as a promising state-of-the-art tool with strong potential to fabricate volumetric liver tissue/organ equivalents using viscosity- and degradation-controlled printable bioinks composed of hydrous microenvironments, and formulations containing living cells and associated supplements. Source of origin, biophysiochemical, or thermomechanical properties and crosslinking reaction kinetics are prerequisites for ideal bioink formulation and realizing the bioprinting process. In this review, we delve into the forecast of the potential future utility of bioprinting technology and the promise of tissue/organ- specific decellularized biomaterials as bioink substrates. Afterward, we outline various methods of decellularization, and the most relevant studies applying decellularized bioinks toward the bioengineering of in vitro liver models. Finally, the challenges and future prospects of decellularized material-based bioprinting in the direction of clinical regenerative medicine are presented to motivate further developments.
    Keywords:  Biofabrication; Bioink; Bioprinting; Decellularization; Liver tissue engineering; Translational regenerative medicine
  3. Int J Bioprint. 2023 ;9(3): 694
      The existing in vitro models for antitumor drug screening have significant limitations. Many compounds that inhibit two-dimensional (2D) cultured cells do not exhibit the same pharmacological effects in vivo, thereby wasting human and material resources and time during drug development. Therefore, it is crucial to develop new models. Three-dimensional (3D) bioprinting technology has greater advantages in constructing human tissues than sandwich culture and organoid construction. We used 3D bioprinting technology to construct a 3D multicellular model of SW480 cells, tumor-associated macrophages, and endothelial cells. The biological activities of the model were evaluated by immunofluorescence, hematoxylin and eosin staining of frozen pathological sections, and transcriptome sequencing. Compared with 3D bioprinted single-cell model (3D printing-S), 3D bioprinted multicellular models (3D printing-M) showed significantly improved expression of tumor-related genes, including hub genes IL1B, FCGR2A, FCGR3A, CYBB, SPI1, CCL2, ITGAM, and ITGB2. Antitumor drug screening experiment showed that the IC50 values of 5-FU, oxaliplatin, and irinotecan in 3D printing-S group/2D culture group were 31.13 μM/12.79 μM, 26.79 μM/0.80 μM, and 16.73 μM/10.45 μM, respectively. Compared with the 3D printing-S group, 3D printing-M group was significantly more resistant to chemotherapy.
    Keywords:  3D bioprinting; Colorectal cancer; Immune microenvironment; Multicellular model
  4. Int J Bioprint. 2023 ;9(3): 680
      26Additive manufacturing technologies offer a multitude of medical applications due to the advances in the development of the materials used to reproduce customized model products. The main problem with these technologies is obtaining the correct cell viability values, and it is where three-dimensional (3D) bioprinting emerges as a very interesting tool that should be studied extensively, as it has significant disadvantages with respect to printability. In this work, the comparison of 3D bioprinting technology in hydrogels and thermoplastics for the development of biomimetic parts is proposed. To this end, the study of the printability of different materials widely used in the literature is proposed, to subsequently test and analyze the parameters that indicate whether these materials could be used to obtain a biomimetic structure with structural guarantees. In order to analyze the materials studied, different tools have been designed to facilitate the quantitative characterization of their printability using 3D printing. For this purpose, different structures have been developed and a characterization methodology has been followed to quantify the printability value of each material in each test to subsequently discard the materials that do not obtain a minimum value in the result. After the study, it was found that only gelatin methacryloyl (GelMA) 5% could generate biomimetic structures faithful to the designed 3D model. Furthermore, by comparing the printing results of the different materials used in 3D bioprinting and consequently establishing the approach of different strategies, it is shown that hydrogels need to be further developed to match the results achieved by thermoplastic materials used for bioprinting.
    Keywords:  3D printing; Bioprinting; Hydrogel; Matrigel; PCL; Printability
  5. Curr Drug Targets. 2023 Jun 05.
      Gelatin is an attractive material for drug delivery and tissue engineering applications due to its excellent biocompatibility and biodegradability, which has been utilized as cell, drug, and gene carriers. Gelatin is less immunogenic compared to collagen and its precursor and retains informational signals, such as RGD (Arg-Gly-Asp) sequence, thus promoting cell adhesion and proliferation. To tune the mechanical strength and bioactivity, gelatin can be easily modified via chemical reactions and physical methods to obtain various derivatives. Furthermore, gelatin-based biomaterials can be achieved through chemical immobilization of specific molecules and physical combination with other biopolymers. This review focuses on the recent advances of gelatin and its derivatives as biomaterials in the field of drug delivery, including cell scaffolds for tissue engineering applications.
    Keywords:  Biopolymers; RGD (Arg-Gly-Asp); drug delivery; gelatin; regenerative medicin; tissue engineering
  6. Int J Bioprint. 2023 ;9(3): 706
      Neurovascular networks play significant roles in the metabolism and regeneration of many tissues and organs in the human body. Blood vessels can transport sufficient oxygen, nutrients, and biological factors, while nerve fibers transmit excitation signals to targeted cells. However, traditional scaffolds cannot satisfy the requirement of stimulating angiogenesis and innervation in a timely manner due to the complexity of host neurovascular networks. Three-dimensional (3D) printing, as a versatile and favorable technique, provides an effective approach to fabricating biological scaffolds with biomimetic architectures and multimaterial compositions, which are capable of regulating multiple cell behaviors. This review paper presents a summary of the current progress in 3D-printed biomaterials for vascularized and innervated tissue regeneration by presenting skin, bone, and skeletal muscle tissues as an example. In addition, we highlight the crucial roles of blood vessels and nerve fibers in the process of tissue regeneration and discuss the future perspectives for engineering novel biomaterials. It is expected that 3D-printed biomaterials with angiogenesis and innervation properties can not only recapitulate the physiological microenvironment of damaged tissues but also rapidly integrate with host neurovascular networks, resulting in accelerated functional tissue regeneration.
    Keywords:  3D printing; Biomaterials; Innervation; Tissue regeneration; Vascularization
  7. Int J Bioprint. 2023 ;9(3): 692
      Spinal cord injury (SCI) causes severe neural tissue damage and motor/sensory dysfunction. Since the injured spinal cord tissue has limited self-regeneration ability, several strategies, including cell therapy, drug delivery, and tissue engineering scaffold implantation, have been employed to treat SCI. However, each of these strategies fails to obtain desirable outcomes due to their respective limitations. In comparison, advanced tissue engineering scaffolds with appropriate topographical features, favorable composition, and sustained drug delivery capability can be employed to recruit endogenous neural stem cells (NSCs), induce neuronal differentiation, and facilitate neuron maturation. This can lead to the regeneration of injured spinal cord tissue and the recovery of motor function. In this study, fiber bundle-reinforced spinal cord extracellular matrix hydrogel scaffolds loaded with oxymatrine (OMT) were produced through nearfield direct write electrospinning. The spinal cord extracellular matrix-based hydrogel was then coated with OMT. The physical/chemical properties and in vitro degradation behavior of the composite scaffolds were investigated. The in vitro cell culture results showed that composite scaffolds loaded with OMT promoted the differentiation of NSCs into neurons and inhibited differentiation into astrocytes. The in vivo results showed that the composite scaffolds loaded with OMT recruited NSCs from the host tissue, promoted neuronal differentiation and axon extension at the lesion site, inhibited glial scar formation at/around the lesion site, and improved the recovery of motor function in rats with SCI. To sum up, 3D-printed microfiber-reinforced spinal cord extracellular matrix hydrogel scaffolds loaded with OMT are promising biomaterials for the treatment of SCI.
    Keywords:  3D bioprinting; Glial scar; Nerve regeneration; Oxymatrine; Spinal cord extracellular matrix; Spinal cord injury
  8. Front Cardiovasc Med. 2023 ;10 1162731
      Introduction: Congenital heart disease is the leading cause of death related to birth defects and affects 1 out of every 100 live births. Induced pluripotent stem cell technology has allowed for patient-derived cardiomyocytes to be studied in vitro. An approach to bioengineer these cells into a physiologically accurate cardiac tissue model is needed in order to study the disease and evaluate potential treatment strategies.Methods: To accomplish this, we have developed a protocol to 3D-bioprint cardiac tissue constructs comprised of patient-derived cardiomyocytes within a hydrogel bioink based on laminin-521.
    Results: Cardiomyocytes remained viable and demonstrated appropriate phenotype and function including spontaneous contraction. Contraction remained consistent during 30 days of culture based on displacement measurements. Furthermore, tissue constructs demonstrated progressive maturation based on sarcomere structure and gene expression analysis. Gene expression analysis also revealed enhanced maturation in 3D constructs compared to 2D cell culture.
    Discussion: This combination of patient-derived cardiomyocytes and 3D-bioprinting represents a promising platform for studying congenital heart disease and evaluating individualized treatment strategies.
    Keywords:  3D-bioprinting; cardiomyocyte; congenital heart disease; hydrogel; hypoplastic left heart syndrome; induced pluripotent stem cell
  9. Macromol Biosci. 2023 Jun 05. e2300152
      Several years have passed since the medical and scientific communities leaned towards tissue engineering as the most promising field to aid bone diseases and defects resulting from degenerative conditions or trauma. Owing to their histocompatibility and non-immunogenicity, bone grafts, precisely autografts, have long been the gold standard in bone tissue therapies. However, due to issues associated with grafting, especially the surgical risks and soaring prices of the procedures, alternatives are being extensively sought and researched. Fibrous and non-fibrous materials, synthetic substitutes or cell-based products are just a few examples of research directions explored as potential solutions. A very promising subgroup of these replacements involves hydrogels. Biomaterials resembling the bone extracellular matrix and therefore acting as three-dimensional scaffolds, providing the appropriate mechanical support and basis for cell growth and tissue regeneration. Additional possibility of use of various stimuli in the form of growth factors, cells, etc., within the hydrogel structure, extends their use as bioactive agent delivery platforms and acts in favor of their further directed development. The aim of this review is to bring the reader closer to the fascinating subject of hydrogel scaffolds and present the potential of these materials, applied in bone and cartilage tissue engineering and regeneration. This article is protected by copyright. All rights reserved.
    Keywords:  bone; hydrogel; scaffold; tissue regeneration
  10. J Prosthet Dent. 2023 Jun 01. pii: S0022-3913(23)00283-4. [Epub ahead of print]
      This technique describes the use of a smartphone application for scanning an ear for 3-dimensional (3D) printing of an auricular prosthesis cast. The intact ear was scanned by using a smartphone and a 3D scan application (Polycam). The standard tessellation language (STL) file of the 3D data was used to produce a mirror image of the ear, which was sent to the 3D printing center where a resin cast was printed. This technique is harmless for the patient compared with radiological imaging methods, more comfortable, and cost-effective and is straightforward for the maxillofacial prosthodontist.
  11. J Prosthodont. 2023 Jun 09.
      The unique anatomical structure of the atrophic edentulous maxilla limits the placement of endosteal root form dental implants without bone grafting and augmentation. Surgical placement of zygomatic implants in an optimal position remains challenging. This technique report illustrates a novel digital guide technology, including the design workflow, application method, and indications for assisting with the placement of zygomatic implants using a bone-supported titanium double-sleeve guide. In addition, when the implant body reaches the zygomatic bone following an intra-sinus path, including ZAGA type 0 and ZAGA type 1 cases, a matching window osteotomy surgical guide is used to locate the lateral window boundary and protect the sinus membrane. With this technique, the surgical procedure is simplified, and the precision of guided zygomatic implant placement is improved. This article is protected by copyright. All rights reserved.
    Keywords:  double-sleeve guide; sinus window osteotomy guide; titanium 3D-printed guide; zygomatic implants
  12. Adv Healthc Mater. 2023 Jun 08. e2300991
      Today's living world is enriched with a myriad of natural biological designs, shaped by billions of years of evolution. Unraveling the construction rules of living organisms offers the potential to create new materials and systems for biomedicine. From the close examination of living organisms, several concepts emerge: hierarchy, pattern repetition, adaptation, and irreducible complexity. All these aspects must be tackled to develop transformative materials with lifelike behavior. This perspective article highlights recent progress in the development of transformative biohybrid systems for applications in the fields of tissue regeneration and biomedicine. Advances in computational simulations and data-driven predictions are also discussed. These tools enable the virtual high-throughput screening of implant design and performance before committing to fabrication, thus reducing the development time and cost of biomimetic and biohybrid constructs. The ongoing progress of imaging methods also constitutes an essential part of this matter in order to validate the computation models and enable longitudinal monitoring. Finally, the current challenges of lifelike biohybrid materials, including reproducibility, ethical considerations, and translation, are discussed. Advances in the development of lifelike materials will open new biomedical horizons, where perhaps what is currently envisioned as science fiction will become a science-driven reality in the future.
    Keywords:  biomedicine; computational simulations; material sciences; molecular imaging; transformative
  13. Int J Bioprint. 2023 ;9(3): 702
      3D-printed biofunctional scaffolds have promising applications in bone tissue regeneration. However, the development of bioinks with rapid internal vascularization capabilities and relatively sustained osteoinductive bioactivity is the primary technical challenge. In this work, we added rat platelet-rich plasma (PRP) to a methacrylated gelatin (GelMA)/methacrylated alginate (AlgMA) system, which was further modified by a nanoclay, laponite (Lap). We found that Lap was effective in retarding the release of multiple growth factors from the PRP-GelMA/AlgMA (PRP-GA) hydrogel and sustained the release for up to 2 weeks. Our in vitro studies showed that the PRP-GA@Lap hydrogel significantly promoted the proliferation, migration, and osteogenic differentiation of rat bone marrow mesenchymal stem cells, accelerated the formation of endothelial cell vascular patterns, and promoted macrophage M2 polarization. Furthermore, we printed hydrogel bioink with polycaprolactone (PCL) layer-by-layer to form active bone repair scaffolds and implanted them in subcutaneous and femoral condyle defects in rats. In vivo experiments showed that the PRP-GA@Lap/PCL scaffolds significantly promoted vascular inward growth and enhanced bone regeneration at the defect site. This work suggests that PRP-based 3D-bioprinted vascularized scaffolds will have great potential for clinical translation in the treatment of bone defects.
    Keywords:  3D bioprinting; Bone regeneration; Platelet-rich plasma; Vascularization
  14. Radiol Phys Technol. 2023 Jun 09.
      A radiotherapy bolus is a tissue-equivalent material placed on the skin to adjust the surface dose of megavoltage X-ray beams used for treatment. In this study, the dosimetric properties of two 3D-printed filament materials, polylactic acid (PLA) and thermoplastic polyether urethane (TPU), used as radiotherapy boluses, were investigated. The dosimetric properties of PLA and TPU were compared with those of several conventional bolus materials and RMI457 Solid Water. Percentage depth-dose (PDD) measurements in the build-up region were performed for all materials using 6 and 10 MV photon treatment beams on Varian linear accelerators. The results showed that the differences in the PDDs of the 3D-printed materials from the RMI457 Solid Water were within 3%, whereas those of the dental wax and SuperFlab gel materials were within 5%. This indicates that PLA and TPU 3D-printed materials are suitable radiotherapy bolus materials.
    Keywords:  3D printing; Bolus; Megavoltage X-ray beams; Percentage depth dose (PDD); Radiotherapy; Surface doses
  15. J Prosthet Dent. 2023 Jun 01. pii: S0022-3913(23)00286-X. [Epub ahead of print]
      Digital smile design and ceramic veneers are described with virtual patient representation. The procedure included facial scanning with a 3D scanner accessory (Structure sensor pro; Occipital Inc) mounted on a tablet computer (iPad; Apple Inc) and an innovative chairside silicone guide to replace the intraoral scan body for a straightforward and user-friendly workflow.