bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024‒03‒24
twelve papers selected by
Seerat Maqsood, University of Teramo

  1. Stem Cells Transl Med. 2024 Mar 19. pii: szae014. [Epub ahead of print]
      The ultimate goal of cardiac tissue engineering is to generate new muscle to repair or replace the damaged heart. This requires advances in stem cell technologies to differentiate billions of cardiomyocytes, together with advanced biofabrication approaches such as 3D bioprinting to achieve the requisite structure and contractile function. In this concise review, we cover recent progress in 3D bioprinting of cardiac tissue using pluripotent stem cell-derived cardiomyocytes, key design criteria for engineering aligned cardiac tissues, and ongoing challenges in the field that must be addressed to realize this goal.
    Keywords:  cardiac; differentiation; myogenesis; stem cells; tissue engineering
  2. J Orthop Trauma. 2024 Apr 01. 38(4S): S9-S12
      SUMMARY: 3D printing technologies have evolved tremendously over the last decade for uses in orthopaedic surgical applications, including being used to manufacture implants for spine, upper extremity, foot and ankle, oncologic, and traumatic reconstructions. Materials used for 3D-printed orthopaedic devices include metals, degradable and nondegradable polymers, and ceramic composites. There are 2 primary advantages for use of 3D printing technologies for orthopaedics: first, the ability to create complex porous lattices that allow for osseointegration and improved implant stability and second, the enablement of complex geometric designs allowing for patient-specific devices based on preoperative imaging. Given continually evolving technology, and the relatively early stage of the materials and 3D printers themselves, the possibilities for continued innovation in orthopaedics are great.
  3. Adv Healthc Mater. 2024 Mar 21. e2304028
      3D bioprinting possesses the potential to revolutionize contemporary methodologies for fabricating tissue models employed in pharmaceutical research and experimental investigations. This is enhanced by combining bioprinting with advanced Organs-on-a-Chip (OOCs), which includes a complex arrangement of multiple cell types representing organ-specific cells, connective tissue and vasculature. However, both OOCs and bioprinting so far demand a high degree of manual intervention, thereby impeding efficiency and inhibiting scalability to meet technological requirements. Through the combination of drop-on-demand bioprinting with robotic handling of microfluidic chips, a print procedure is achieved that is proficient in managing three distinct tissue models on a chip within only a minute, as well as capable of consecutively processing numerous OOCs without manual intervention. This process rests upon the development of a post-printing sealable microfluidic chip, that is compatible with different types of 3D-bioprinters and easily connected a perfusion system. The capabilities of the automized bioprint process are showcased through the creation of a multicellular and vascularized liver carcinoma model on chip. The process achieves full vascularization and stable microvascular network formation over 14 days of culture time, with pronounced spheroidal cell growth and albumin secretion of HepG2 serving as a representative cell model. This article is protected by copyright. All rights reserved.
    Keywords:  Bioprinting; Organ‐on‐a‐Chip; robotics; vascularization
  4. Acta Biomater. 2024 Mar 15. pii: S1742-7061(24)00141-7. [Epub ahead of print]
      Reconstruction of the human auricle remains a formidable challenge for plastic surgeons. Autologous costal cartilage grafts and alloplastic implants are technically challenging, and aesthetic and/or tactile outcomes are frequently suboptimal. Using a small animal "bioreactor", we have bioengineered full-scale ears utilizing decellularized cartilage xenograft placed within a 3D-printed external auricular scaffold that mimics the size, shape, and biomechanical properties of the native human auricle. The full-scale polylactic acid ear scaffolds were 3D-printed based upon data acquired from 3D photogrammetry of an adult ear. Ovine costal cartilage was processed either through mincing (1 mm3) or zesting (< 0.5 mm3), and then fully decellularized and sterilized. At explantation, both the minced and zested neo-ears maintained the size and contour complexities of the scaffold topography with steady tissue ingrowth through 6 months in vivo. A mild inflammatory infiltrate at 3 months was replaced by homogenous fibrovascular tissue ingrowth enveloping individual cartilage pieces at 6 months. All ear constructs were pliable, and the elasticity was confirmed by biomechanical analysis. Longer-term studies of the neo-ears with faster degrading biomaterials will be warranted for future clinical application. STATEMENT OF SIGNIFICANCE: Accurate reconstruction of the human auricle has always been a formidable challenge to plastic surgeons. In this article, we have bioengineered full-scale ears utilizing decellularized cartilage xenograft placed within a 3D-printed external auricular scaffold that mimic the size, shape, and biomechanical properties of the native human auricle. Longer-term studies of the neo-ears with faster degrading biomaterials will be warranted for future clinical application.
    Keywords:  cartilage; ear reconstruction; scaffold; tissue engineering
  5. ACS Appl Mater Interfaces. 2024 Mar 20.
      Surgical removal of tumor tissue remains the primary clinical approach for addressing breast cancer; however, complete tumor excision is challenging, and the remaining tumor cells can lead to tumor recurrence and metastasis over time, which substantially deteriorates the life quality of the patients. With the aim to improve local cancer radiotherapy, this work reports the fabrication of alginate (Alg) scaffolds containing bovine serum albumin (BSA)-coated bismuth sulfide (Bi2S3@BSA) nanoradiosensitizers using three-dimensional (3D) printing. Under single-dose X-ray irradiation in vitro, Alg-Bi2S3@BSA scaffolds significantly increase the formation of reactive oxygen species, enhance the inhibition of breast cancer cells, and suppress their colony formation capacity. In addition, scaffolds implanted under tumor tissue in murine model show high therapeutic efficacy by reducing the tumor volume growth rate under single-dose X-ray irradiation, while histological observation of main organs reveals no cytotoxicity or side effects. 3D-printed Alg-Bi2S3@BSA scaffolds produced with biocompatible and biodegradable materials may potentially lower the recurrence and metastasis rates in breast cancer patients by inhibiting residual tumor cells following postsurgery as well as exhibit anticancer properties in other solid tumors.
    Keywords:  3D printing; bismuth sulfide; breast cancer; implantable; radiotherapy; scaffold
  6. Heliyon. 2024 Mar 15. 10(5): e27328
      Rapid advancements in the field of 3D printing in the last several decades have made it possible to produce complex and unique parts with remarkable precision and accuracy. Investigating the use of 3D printing to create various high-performance materials is a relatively new field that is expanding exponentially worldwide. Automobile, biomedical, construction, aerospace, electronics, and metal and alloy industries are among the most prolific users of 3D printing technology. Modern 3D printing technologies, such as polymer matrices that use fiber-reinforced composites (FRCs) to enhance the mechanical qualities of printed components greatly, have been useful to several industries. High stiffness and tensile strength lightweight components are developed from these materials. Fiber-reinforced composites have a wide range of applications, such as military vehicles, fighter aircraft, underwater structures, shelters, and warfare equipment. Fabricating FRCs using fused deposition modeling (FDM) is also advantageous over other 3D printing methods due to its low cost and ease of operation. The impact of different continuous fiber and matrix polymer selections on FRC performance is covered in this review paper. We will also evaluate the important parameters influencing FRC characteristics and review the most recent equipment and methods for fabricating FRCs. Furthermore, the challenges associated with 3D printing fiber-reinforced composites are covered. The constraints of present technology have also been used to identify future research areas.
    Keywords:  3D printing; Additive manufacturing; Fiber reinforced composites; Fused deposition modeling; Polymer matrix
  7. Med Rev (2021). 2024 Feb;4(1): 68-85
      Cardiovascular research has heavily relied on studies using patient samples and animal models. However, patient studies often miss the data from the crucial early stage of cardiovascular diseases, as obtaining primary tissues at this stage is impracticable. Transgenic animal models can offer some insights into disease mechanisms, although they usually do not fully recapitulate the phenotype of cardiovascular diseases and their progression. In recent years, a promising breakthrough has emerged in the form of in vitro three-dimensional (3D) cardiovascular models utilizing human pluripotent stem cells. These innovative models recreate the intricate 3D structure of the human heart and vessels within a controlled environment. This advancement is pivotal as it addresses the existing gaps in cardiovascular research, allowing scientists to study different stages of cardiovascular diseases and specific drug responses using human-origin models. In this review, we first outline various approaches employed to generate these models. We then comprehensively discuss their applications in studying cardiovascular diseases by providing insights into molecular and cellular changes associated with cardiovascular conditions. Moreover, we highlight the potential of these 3D models serving as a platform for drug testing to assess drug efficacy and safety. Despite their immense potential, challenges persist, particularly in maintaining the complex structure of 3D heart and vessel models and ensuring their function is comparable to real organs. However, overcoming these challenges could revolutionize cardiovascular research. It has the potential to offer comprehensive mechanistic insights into human-specific disease processes, ultimately expediting the development of personalized therapies.
    Keywords:  cardiac microtissues; cardiac organoids; organ-on-a-chip; pluripotent stem cells; three-dimensional (3D) models; vessel organoids
  8. Biomater Sci. 2024 Mar 21.
      Bone defects are a common complication of bone diseases, which often affect the quality of life and mental health of patients. The use of biomimetic bone scaffolds loaded with bioactive substances has become a focal point in the research on bone defect repair. In this study, composite scaffolds resembling bone tissue were created using nacre powder (NP) and sodium alginate (SA) through 3D printing. These scaffolds exhibit several physiological structural and mechanical characteristics of bone tissue, such as suitable porosity, an appropriate pore size, applicable degradation performance and satisfying the mechanical requirements of cancellous bone, etc. Then, platelet-rich fibrin (PRF), containing a mass of growth factors, was loaded on the NP/SA scaffolds. This was aimed to fully maximize the synergistic effect with NP, thereby accelerating bone tissue regeneration. Overall, this study marks the first instance of preparing a bionic bone structure scaffold containing NP by 3D printing technology, which is combined with PRF to further accelerate bone regeneration. These findings offer a new treatment strategy for bone tissue regeneration in clinical applications.
  9. Bioact Mater. 2024 Jun;36 317-329
      The integrative regeneration of both articular cartilage and subchondral bone remains an unmet clinical need due to the difficulties of mimicking spatial complexity in native osteochondral tissues for artificial implants. Layer-by-layer fabrication strategies, such as 3D printing, have emerged as a promising technology replicating the stratified zonal architecture and varying microstructures and mechanical properties. However, the dynamic and circulating physiological environments, such as mass transportation or cell migration, usually distort the pre-confined biological properties in the layered implants, leading to undistinguished spatial variations and subsequently inefficient regenerations. This study introduced a biomimetic calcified interfacial layer into the scaffold as a compact barrier between a cartilage layer and a subchondral bone layer to facilitate osteogenic-chondrogenic repair. The calcified interfacial layer consisting of compact polycaprolactone (PCL), nano-hydroxyapatite, and tasquinimod (TA) can physically and biologically separate the cartilage layer (TA-mixed, chondrocytes-load gelatin methacrylate) from the subchondral bond layer (porous PCL). This introduction preserved the as-designed independent biological environment in each layer for both cartilage and bone regeneration, successfully inhibiting vascular invasion into the cartilage layer and preventing hyaluronic cartilage calcification owing to devascularization of TA. The improved integrative regeneration of cartilage and subchondral bone was validated through gross examination, micro-computed tomography (micro-CT), and histological and immunohistochemical analyses based on an in vivo rat model. Moreover, gene and protein expression studies identified a key role of Caveolin (CAV-1) in promoting angiogenesis through the Wnt/β-catenin pathway and indicated that TA in the calcified layer blocked angiogenesis by inhibiting CAV-1.
    Keywords:  3D-printed scaffold; CAV-1; Calcified interfacial layer; Osteochondral regeneration; Tasquinimod
  10. J Prosthodont. 2024 Mar 21.
      This technique presents a new fabrication workflow for a three-dimensional (3D) printed custom tray, which duplicates the morphology of the treatment denture for maxillofacial prostheses using an intraoral scanner, computer-aided design (CAD) software, and a 3D printer. A 70-year-old man underwent reconstruction of segmental mandibulectomy for mandibular osteoblastoma, followed by implant placement and secondary surgery. During the surgical treatment, a treatment denture was fabricated to restore oral function and determine the morphology of the definitive denture. To create the definitive denture with the same morphology as the treatment denture a custom tray was fabricated with the denture morphology after chairside adjustments. The oral cavity was scanned using an intraoral scanner, and the data acquired were imported into general-purpose CAD software, adjusted, and imported into a 3D printer to produce the custom tray. This was fitted into the patient's mouth without any issues, and closed tray impressions were made with impression caps for the locator attachments on the implant body. The morphology of the treatment denture was replicated in the definitive denture by making a silicon impression of the cameo surface at the fabrication of the cast after impression making. In this technique, the morphology of the treatment denture was transferred accurately to the definitive implant partial denture by leveraging existing digital technology. This method represents a practical approach for partial denture fabrication, including maxillofacial defects with complex denture configurations.
    Keywords:  3D printer; CAD‐CAM; Custom tray; Intraoral scanner; Maxillofacial prostheses
  11. Knee Surg Sports Traumatol Arthrosc. 2024 Mar 20.
      PURPOSE: The aim of this study was to evaluate the role of a novel total meniscal implant in promoting meniscal regeneration and protecting articular cartilage in a rabbit model for 3 and 6 months.METHODS: Thirty-six New Zealand rabbits were selected and divided into poly(ɛ-caprolactone) (PG-Pg) scaffold group, meniscectomy group and sham group. In this study, it was investigated whether PG-Pg scaffold can prevent articular cartilage degeneration and promote tissue degeneration, and its mechanical properties at 3 and 6 months after surgery were also explored.
    RESULT: The degree of articular cartilage degeneration was significantly lower in the PG-Pg scaffold group than in the meniscectomy group. The number of chondrocytes increased in the PG-Pg scaffold at 3 and 6 months, while a gradual increase in the mechanical properties of the PG-Pg stent was observed from 6 months.
    CONCLUSION: The PG-Pg scaffold slows down the degeneration of articular cartilage, promotes tissue regeneration and improves biomechanical properties after meniscectomy. This novel meniscus scaffold holds promise for enhancing surgical strategies and delivering superior long-term results for individuals with severe meniscus tears.
    Keywords:  graphene; meniscal injury; poly(vinyl alcohol); poly(ɛ-caprolactone); scaffold
  12. Pharm Dev Technol. 2024 Mar 22. 1-14
      We recently reported the potential of a new gallium compound, gallium acetylacetonate (GaAcAc) in combating osteoclastic bone resorption through inhibition of osteoclast differentiation and function. Herein, we focused on 3D-printed polylactic acid scaffolds that were loaded with GaAcAc and investigated the impact of scaffold pretreatment with polydopamine (PDA) or sodium hydroxide (NaOH). We observed a remarkable increase in scaffold hydrophilicity with PDA or NaOH pretreatment while biocompatibility and in vitro degradation were not affected. NaOH-pretreated scaffolds showed the highest amount of GaAcAc loading when compared to other scaffolds (p < 0.05). NaOH-pretreated scaffolds with GaAcAc loading showed effective reduction of osteoclast counts and size. The trend was supported by suppression of key osteoclast differentiation markers such as NFAT2, c-Fos, TRAF6, & TRAP. All GaAcAc-loaded scaffolds, regardless of surface pretreatment, were effective in inhibiting osteoclast function as evidenced by reduction in the number of resorptive pits in bovine cortical bone slices (p < 0.01). The suppression of osteoclast function according to the type of scaffold followed the ranking: GaAcAc loading without surface pretreatment > GaAcAc loading with NaOH pretreatment > GaAcAc loading with PDA pretreatment. Additional studies will be needed to fully elucidate the impact of surface pretreatment on the efficacy and safety of GaAcAc-loaded 3D-printed scaffolds.
    Keywords:  Osteoclasts; fused deposition; gallium; osteoblasts; polylactic acid; three-dimensional printing