bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024‒01‒28
twenty-one papers selected by
Seerat Maqsood, University of Teramo

  1. Gels. 2023 Dec 21. pii: 8. [Epub ahead of print]10(1):
      Three-dimensional (3D) printing, also known as additive manufacturing, has revolutionized the production of physical 3D objects by transforming computer-aided design models into layered structures, eliminating the need for traditional molding or machining techniques. In recent years, hydrogels have emerged as an ideal 3D printing feedstock material for the fabrication of hydrated constructs that replicate the extracellular matrix found in endogenous tissues. Hydrogels have seen significant advancements since their first use as contact lenses in the biomedical field. These advancements have led to the development of complex 3D-printed structures that include a wide variety of organic and inorganic materials, cells, and bioactive substances. The most commonly used 3D printing techniques to fabricate hydrogel scaffolds are material extrusion, material jetting, and vat photopolymerization, but novel methods that can enhance the resolution and structural complexity of printed constructs have also emerged. The biomedical applications of hydrogels can be broadly classified into four categories-tissue engineering and regenerative medicine, 3D cell culture and disease modeling, drug screening and toxicity testing, and novel devices and drug delivery systems. Despite the recent advancements in their biomedical applications, a number of challenges still need to be addressed to maximize the use of hydrogels for 3D printing. These challenges include improving resolution and structural complexity, optimizing cell viability and function, improving cost efficiency and accessibility, and addressing ethical and regulatory concerns for clinical translation.
    Keywords:  3D printing; additive manufacturing; biomedical engineering; hydrogels; polymers; tissue engineering and regenerative medicine
  2. Curr Med Chem. 2024 Jan 22.
      Three-dimensional printing (3DP) has gained popularity among scientists and researchers in every field due to its potential to drastically reduce energy costs for the production of customised products by utilising less energy-intensive machines as well as minimising material waste. The 3D printing technology is an additive manufacturing approach that uses material layer-by-layer fabrication to produce the digitally specified 3D model. The use of 3D printing technology in the pharmaceutical sector has the potential to revolutionise research and development by providing a quick and easy means to manufacture personalised one-off batches, each with unique dosages, distinct substances, shapes, and sizes, as well as variable release rates. This overview addresses the concept of 3D printing, its evolution, and its operation, as well as the most popular types of 3D printing processes utilised in the health care industry. It also discusses the application of these cutting-edge technologies to the pharmaceutical industry, advancements in various medical fields and medical equipment, 3D bioprinting, the most recent initiatives to combat COVID-19, regulatory frameworks, and the major challenges that this technology currently faces. In addition, we attempt to provide some futuristic approaches to 3DP applications.
    Keywords:  3D bioprinting.; 3D printed equipment; 3D printing techniques; COVID-19 treatment; DOP; EHD; EMP; SLS; drug delivery system; inkjet; personalized medicines; vat photopolymerization
  3. Biofabrication. 2024 Jan 26.
      Tissue engineering has emerged as a strategy for producing functional tissues and organs to treat diseases and injuries. Many chronic conditions directly or indirectly affect normal blood vessel functioning, necessary for material exchange and transport through the body and within tissue-engineered constructs. The interest in vascular tissue engineering is due to two reasons: 1) functional grafts can be used to replace diseased blood vessels, and 2) engineering effective vasculature within other engineered tissues enables connection with the host's circulatory system, supporting their survival. Among various practices, (bio)printing has emerged as a powerful tool to engineer biomimetic constructs. This has been made possible with precise control of cell deposition and matrix environment along with the advancements in biomaterials. (Bio)printing has been used for both engineering stand-alone vascular grafts as well as vasculature within engineered tissues for regenerative applications. In this review article, we discuss various conditions associated with blood vessels, the need for artificial blood vessels, the anatomy and physiology of different blood vessels, available 3D (bio)printing techniques to fabricate tissue-engineered vascular grafts and vasculature in scaffolds, and the comparison among the different techniques. We conclude our review with a brief discussion about future opportunities in the area of blood vessel tissue engineering.
    Keywords:  Biomaterials; Bioprinting; Blood Vessels; Scaffolds; Vascularization
  4. J 3D Print Med. 2023 Jun;7(2):
      Heart diseases cause over 17.9 million total deaths globally, making them the leading source of mortality. The aim of this review is to describe the characteristic mechanical, chemical and cellular properties of human cardiac tissue and how these properties can be mimicked in 3D bioprinted tissues. Furthermore, the authors review how current healthy cardiac models are being 3D bioprinted using extrusion-, laser- and inkjet-based printers. The review then discusses the pathologies of cardiac diseases and how bioprinting could be used to fabricate models to study these diseases and potentially find new drug targets for such diseases. Finally, the challenges and future directions of cardiac disease modeling using 3D bioprinting techniques are explored.
    Keywords:  bioprinting; cardiac tissues; cardiomyocytes; disease modelling; review; stem cells
  5. ACS Biomater Sci Eng. 2024 Jan 22.
      3D printing has become increasingly popular in the field of bone tissue engineering. However, the mechanical properties, biocompatibility, and porosity of the 3D printed bone scaffolds are major requirements for tissue regeneration and implantation as well. Designing the scaffold architecture in accordance with the need to create better mechanical and biological stimuli is necessary to achieve unique scaffold properties. To accomplish this, different 3D designing strategies can be utilized with the help of the scaffold design library and artificial intelligence (AI). The implementation of AI to assist the 3D printing process can enable it to predict, adapt, and control the parameters on its own, which lowers the risk of errors. This Review emphasizes 3D design and fabrication of bone scaffold using different materials and the use of AI-aided 3D printing strategies. Also, the adaption of AI to 3D printing helps to develop patient-specific scaffolds based on different requirements, thus providing feedback and adequate data for reproducibility, which can be improvised in the future. These printed scaffolds can also serve as an alternative to preclinical animal test models to cut costs and prevent immunological interference.
    Keywords:  artificial intelligence aided modeling and 3D printing; bone tissue engineering; clinical trials; preclinical study models; scaffold architecture
  6. Mater Today Bio. 2024 Feb;24 100948
      Articular cartilage injury is a frequent worldwide disease, while effective treatment is urgently needed. Due to lack of blood vessels and nerves, the ability of cartilage to self-repair is limited. Despite the availability of various clinical treatments, unfavorable prognoses and complications remain prevalent. However, the advent of tissue engineering and regenerative medicine has generated considerable interests in using biomaterials for articular cartilage repair. Nevertheless, there remains a notable scarcity of comprehensive reviews that provide an in-depth exploration of the various strategies and applications. Herein, we present an overview of the primary biomaterials and bioactive substances from the tissue engineering perspective to repair articular cartilage. The strategies include regeneration, substitution, and immunization. We comprehensively delineate the influence of mechanically supportive scaffolds on cellular behavior, shedding light on emerging scaffold technologies, including stimuli-responsive smart scaffolds, 3D-printed scaffolds, and cartilage bionic scaffolds. Biologically active substances, including bioactive factors, stem cells, extracellular vesicles (EVs), and cartilage organoids, are elucidated for their roles in regulating the activity of chondrocytes. Furthermore, the composite bioactive scaffolds produced industrially to put into clinical use, are also explicitly presented. This review offers innovative solutions for treating articular cartilage ailments and emphasizes the potential of biomaterials for articular cartilage repair in clinical translation.
    Keywords:  Biologically active substances; Cartilage; Clinical practice; Mechanically supported scaffolds; Repair strategies
  7. Bioengineering (Basel). 2023 Dec 27. pii: 32. [Epub ahead of print]11(1):
      Notably, 3D-printed flexible and wearable biosensors have immense potential to interact with the human body noninvasively for the real-time and continuous health monitoring of physiological parameters. This paper comprehensively reviews the progress in 3D-printed wearable biosensors. The review also explores the incorporation of nanocomposites in 3D printing for biosensors. A detailed analysis of various 3D printing processes for fabricating wearable biosensors is reported. Besides this, recent advances in various 3D-printed wearable biosensors platforms such as sweat sensors, glucose sensors, electrocardiography sensors, electroencephalography sensors, tactile sensors, wearable oximeters, tattoo sensors, and respiratory sensors are discussed. Furthermore, the challenges and prospects associated with 3D-printed wearable biosensors are presented. This review is an invaluable resource for engineers, researchers, and healthcare clinicians, providing insights into the advancements and capabilities of 3D printing in the wearable biosensor domain.
    Keywords:  3D printing; biomedical; health monitoring; nanocomposites; wearable biosensors
  8. J Clin Med. 2024 Jan 20. pii: 599. [Epub ahead of print]13(2):
      Introduction: Interest in 3D printing for orthopedic surgery has been increasing since its progressive adoption in most of the hospitals around the world. The aim of the study is to describe all the current applications of 3D printing in patients undergoing hip surgery of any type at the present time. Materials and Methods: We conducted a systematic narrative review of publications indexed in MedLine through the search engine PubMed, with the following parameters: 3D printing AND (orthopedics OR traumatology) NOT tissue engineering NOT scaffold NOT in vitro and deadline 31 July 2023. After reading the abstracts of the articles, papers were selected according to the following criteria: full text in English or Spanish and content related to hip surgery. Those publications involving experimental studies (in vitro or with anatomical specimens) or 3D printing outside of hospital facilities as well as 3D-printed commercial implants were excluded. Results are presented as a reference guide classified by disease, including the used software and the steps required for the development of the idea. Results: We found a total of 27 indications for in-house 3D printing for hip surgery, which are described in the article. Conclusions: There are many surgical applications of 3D printing in hip surgery, most of them based on CT images. Most of the publications lack evidence, and further randomized studies should be encouraged to assess the advantages of these indications.
    Keywords:  3D printing; PSI; hip surgery
  9. Dent J (Basel). 2023 Dec 19. pii: 1. [Epub ahead of print]12(1):
      PURPOSE: This narrative review aims to provide an overview of the mechanisms of 3D printing, the dental materials relevant to each mechanism, and the possible applications of these materials within different areas of dentistry.METHODS: Subtopics within 3D printing technology in dentistry were identified and divided among five reviewers. Electronic searches of the Medline (PubMed) database were performed with the following search keywords: 3D printing, digital light processing, stereolithography, digital dentistry, dental materials, and a combination of the keywords. For this review, only studies or review papers investigating 3D printing technology for dental or medical applications were included. Due to the nature of this review, no formal evidence-based quality assessment was performed, and the search was limited to the English language without further restrictions.
    RESULTS: A total of 64 articles were included. The significant applications, applied materials, limitations, and future directions of 3D printing technology were reviewed. Subtopics include the chronological evolution of 3D printing technology, the mechanisms of 3D printing technologies along with different printable materials with unique biomechanical properties, and the wide range of applications for 3D printing in dentistry.
    CONCLUSIONS: This review article gives an overview of the history and evolution of 3D printing technology, as well as its associated advantages and disadvantages. Current 3D printing technologies include stereolithography, digital light processing, fused deposition modeling, selective laser sintering/melting, photopolymer jetting, powder binder, and 3D laser bioprinting. The main categories of 3D printing materials are polymers, metals, and ceramics. Despite limitations in printing accuracy and quality, 3D printing technology is now able to offer us a wide variety of potential applications in different fields of dentistry, including prosthodontics, implantology, oral and maxillofacial, orthodontics, endodontics, and periodontics. Understanding the existing spectrum of 3D printing applications in dentistry will serve to further expand its use in the dental field. Three-dimensional printing technology has brought about a paradigm shift in the delivery of clinical care in medicine and dentistry. The clinical use of 3D printing has created versatile applications which streamline our digital workflow. Technological advancements have also paved the way for the integration of new dental materials into dentistry.
    Keywords:  3D printing; dental material; digital dentistry; digital light processing; stereolithography
  10. Biomimetics (Basel). 2024 Jan 19. pii: 55. [Epub ahead of print]9(1):
      The successful regeneration of large-size bone defects remains one of the most critical challenges faced in orthopaedics. Recently, 3D printing technology has been widely used to fabricate reliable, reproducible and economically affordable scaffolds with specifically designed shapes and porosity, capable of providing sufficient biomimetic cues for a desired cellular behaviour. Natural or synthetic polymers reinforced with active bioceramics and/or graphene derivatives have demonstrated adequate mechanical properties and a proper cellular response, attracting the attention of researchers in the bone regeneration field. In the present work, 3D-printed graphene nanoplatelet (GNP)-reinforced polylactic acid (PLA)/hydroxyapatite (HA) composite scaffolds were fabricated using the fused deposition modelling (FDM) technique. The in vitro response of the MC3T3-E1 pre-osteoblasts and RAW 264.7 macrophages revealed that these newly designed scaffolds exhibited various survival rates and a sustained proliferation. Moreover, as expected, the addition of HA into the PLA matrix contributed to mimicking a bone extracellular matrix, leading to positive effects on the pre-osteoblast osteogenic differentiation. In addition, a limited inflammatory response was also observed. Overall, the results suggest the great potential of the newly developed 3D-printed composite materials as suitable candidates for bone tissue engineering applications.
    Keywords:  3D printing; PLA-HA matrix; bone tissue regeneration; graphene; immune response; osteogenic differentiation
  11. ACS Appl Mater Interfaces. 2024 Jan 23.
      The creation of 3D biomimetic composite structures has important applications in tissue engineering, lightweight structures, drug delivery, and sensing. Previous approaches in fabricating 3D biomimetic composites have relied on blending or assembling chemically synthesized molecules or structures, making it challenging to achieve precise control of the size, geometry, and internal structure of the biomimetic composites. Here, we present a new approach for the creation of 3D bone-mimetic biocomposites with precisely controlled shape, hierarchical structure, and functionalities. Our approach is based on the integration of programmable microbial biosynthesis with 3D printing of gas-permeable and customizable bioreactors. The organic and inorganic components are bacterial cellulose and calcium hydroxyapatite via a mineral precursor, which are generated by Komagataeibacter xylinus and Bacillus simplex P6A, respectively, in 3D-printed silicone bioreactors in consecutive culturing cycles. This study is of high significance to biocomposites, biofabrication, and tissue engineering as it paves the way for the synergistic integration of microbial biosynthesis and additive manufacturing.
    Keywords:  3D printing; bacterial cellulose; biomimetic composites; microbial synthesis; nanocomposites
  12. Micromachines (Basel). 2023 Dec 30. pii: 83. [Epub ahead of print]15(1):
      Limitations of bone defect reconstruction include poor bone healing and osteointegration with acrylic cements, lack of strength with bone putty/paste, and poor osteointegration. Tissue engineering aims to bridge these gaps through the use of bioactive implants. However, there is often a risk of infection and biofilm formation associated with orthopedic implants, which may develop anti-microbial resistance. To promote bone repair while also locally delivering therapeutics, 3D-printed implants serve as a suitable alternative. Soft, nanoporous 3D-printed filaments made from a thermoplastic polyurethane and polyvinyl alcohol blend, LAY-FOMM and LAY-FELT, have shown promise for drug delivery and orthopedic applications. Here, we compare 3D printability and sustained antibiotic release kinetics from two types of commercial 3D-printed porous filaments suitable for bone tissue engineering applications. We found that both LAY-FOMM and LAY-FELT could be consistently printed into scaffolds for drug delivery. Further, the materials could sustainably release Tetracycline over 3 days, independent of material type and infill geometry. The drug-loaded materials did not show any cytotoxicity when cultured with primary human fibroblasts. We conclude that both LAY-FOMM and LAY-FELT 3D-printed scaffolds are suitable devices for local antibiotic delivery applications, and they may have potential applications to prophylactically reduce infections in orthopedic reconstruction surgery.
    Keywords:  antibiotics; antimicrobial resistance; bone defect; drug delivery; tissue engineering
  13. Macromol Rapid Commun. 2024 Jan 25. e2300661
      Photocuring 3D printing of hydrogels, with sophisticated, delicate structures and biocompatibility, have attracted significant attentions by researchers and possessed promising application in the fields of tissue engineering and flexible devices. After years of development, photocuring 3D printing technologies and hydrogel inks have made great progress. Herein, we review the techniques of photocuring 3D printing of hydrogels, including Direct Ink Writing (DIW), Stereolithography (SLA), Digital Light Processing (DLP), Continuous Liquid Interface Production (CLIP), Volumetric additive manufacturing (VAM) and Two Photon Polymerization (TPP). Furtherly, the raw materials for hydrogel inks (photocurable polymers, monomers, photoinitiators and additives) and applications in tissue engineering and flexible devices are also reviewed. At last, the current challenges and future perspectives of photocuring 3D printing of hydrogels are discussed. This article is protected by copyright. All rights reserved.
    Keywords:  3D printing; hydrogels; photopolymerization
  14. Molecules. 2024 Jan 09. pii: 319. [Epub ahead of print]29(2):
      Additive manufacturing (AM), commonly referred to as 3D printing, has revolutionized the manufacturing landscape by enabling the intricate layer-by-layer construction of three-dimensional objects. In contrast to traditional methods relying on molds and tools, AM provides the flexibility to fabricate diverse components directly from digital models without the need for physical alterations to machinery. Four-dimensional printing is a revolutionary extension of 3D printing that introduces the dimension of time, enabling dynamic transformations in printed structures over predetermined periods. This comprehensive review focuses on polymeric materials in 3D printing, exploring their versatile processing capabilities, environmental adaptability, and applications across thermoplastics, thermosetting materials, elastomers, polymer composites, shape memory polymers (SMPs), including liquid crystal elastomer (LCE), and self-healing polymers for 4D printing. This review also examines recent advancements in microvascular and encapsulation self-healing mechanisms, explores the potential of supramolecular polymers, and highlights the latest progress in hybrid printing using polymer-metal and polymer-ceramic composites. Finally, this paper offers insights into potential challenges faced in the additive manufacturing of polymer composites and suggests avenues for future research in this dynamic and rapidly evolving field.
    Keywords:  3D printing; 4D printing; additive manufacturing; polymers; shape memory
  15. Bioact Mater. 2024 Apr;34 338-353
      The osteochondral defects (OCDs) resulting from the treatment of giant cell tumors of bone (GCTB) often present two challenges for clinicians: tumor residue leading to local recurrence and non-healing of OCDs. Therefore, this study focuses on developing a double-layer PGPC-PGPH scaffold using shell-core structure nanofibers to achieve "spatiotemporal control" for treating OCDs caused by GCTB. It addresses two key challenges: eliminating tumor residue after local excision and stimulating osteochondral regeneration in non-healing OCD cases. With a shell layer of protoporphyrin IX (PpIX)/gelatin (GT) and inner cores containing chondroitin sulfate (CS)/poly(lactic-co-glycolic acid) (PLGA) or hydroxyapatite (HA)/PLGA, coaxial electrospinning technology was used to create shell-core structured PpIX/GT-CS/PLGA and PpIX/GT-HA/PLGA nanofibers. These nanofibers were shattered into nano-scaled short fibers, and then combined with polyethylene oxide and hyaluronan to formulate distinct 3D printing inks. The upper layer consists of PpIX/GT-CS/PLGA ink, and the lower layer is made from PpIX/GT-HA/PLGA ink, allowing for the creation of a double-layer PGPC-PGPH scaffold using 3D printing technique. After GCTB lesion removal, the PGPC-PGPH scaffold is surgically implanted into the OCDs. The sonosensitizer PpIX in the shell layer undergoes sonodynamic therapy to selectively damage GCTB tissue, effectively eradicating residual tumors. Subsequently, the thermal effect of sonodynamic therapy accelerates the shell degradation and release of CS and HA within the core layer, promoting stem cell differentiation into cartilage and bone tissues at the OCD site in the correct anatomical position. This innovative scaffold provides temporal control for anti-tumor treatment followed by tissue repair and spatial control for precise osteochondral regeneration.
    Keywords:  Double-layered scaffold; Giant cell tumors of bone; Osteochondral regeneration; Shell-core structure; Spatiotemporal control
  16. J Funct Biomater. 2023 Dec 22. pii: 7. [Epub ahead of print]15(1):
      Along with the rapid and extensive advancements in the 3D printing field, a diverse range of uses for 3D printing have appeared in the spectrum of medical applications. Vat photopolymerization (VPP) stands out as one of the most extensively researched methods of 3D printing, with its main advantages being a high printing speed and the ability to produce high-resolution structures. A major challenge in using VPP 3D-printed materials in medicine is the general incompatibility of standard VPP resin mixtures with the requirements of biocompatibility and biofunctionality. Instead of developing completely new materials, an alternate approach to solving this problem involves adapting existing biomaterials. These materials are incompatible with VPP 3D printing in their pure form but can be adapted to the VPP chemistry and general process through the use of innovative mixtures and the addition of specific pre- and post-printing steps. This review's primary objective is to highlight biofunctional and biocompatible materials that have been adapted to VPP. We present and compare the suitability of these adapted materials to different medical applications and propose other biomaterials that could be further adapted to the VPP 3D printing process in order to fulfill patient-specific medical requirements.
    Keywords:  3D printing; additive manufacturing; biocompatible; digital light processing; stereolitography; vat photopolymerization
  17. Int J Clin Pediatr Dent. 2023 Nov;16(Suppl 3): 321-326
      Aim and objective: The present case report comprehensively illustrates the use of a novel digital three-dimensional (3D) printed band and loop space maintainer [computer-aided design and computer-aided manufacturing (CAD/CAM)] for the guidance of eruption with their distinctive attribute of reduced chairside time in a home-schooled autistic child.Background: Three-dimensional (3D) printing is a promising and emerging technology in the arena of dentistry based on CAD/CAM. It has led to the production of customized 3D objects or patient-specific prostheses with accurate results achieved in a time-saving manner. 3D printing has been employed in several latitudes of dentistry; however, the applications are few in the field of pediatric dentistry.
    Case description: The paper describes the space management of an autistic child for the missing mandibular left primary second molar through the novel technique of 3D printed band and loop space maintainer.
    Clinical significance: The novel technique has definite advantages, including high precision, accuracy, fast production, and reduced patient exposure to dentists and vice versa, which has been the need of the hour since the advent of the coronavirus disease of 2019 (COVID-19) pandemic.
    Conclusion: Three-dimensional (3D) printing minimizes dental aerosol-generated exposure by decreasing chairside procedural time and minimizing procedural sitting. The cost-benefit analysis, as applied to the Indian scenario, has also been computed, which makes it equally acceptable. Moreover, 3D printing reduces material waste production, offering a greener and environmentally friendly option in the coming years. The future of pediatric dentistry will evolve with signs of progress in the latest materials and technologies.
    How to cite this article: Yangdol P, Kalra N, Tyagi R, et al. Three-dimensional Printing Technology: Patient-friendly and Time-saving Approach for Space Management in an Autistic Child in COVID-19 Times. Int J Clin Pediatr Dent 2023;16(S-3):S321-S326.
    Keywords:  Case report; Computer-aided design and computer-aided manufacturing; Digital dentistry; Pediatric dentistry; Space maintainer; Three-dimensional printing
  18. Life Sci Space Res (Amst). 2024 Feb;pii: S2214-5524(23)00060-3. [Epub ahead of print]40 158-165
      Space foods closely associate with the performance and mental health of astronauts. Over the years, a range of manufacturing technologies have been explored and advancements in food 3D printing can provide answers to certain existing challenges and revolutionize the way foods are prepared for space exploration missions. Apart from the nutrition and satiety perspective, product shelf-life, variety, personalization, and the need for customized diets are critical considerations. In such long-duration human-crewed space missions, under microgravity conditions and exposure to space, psychological factors heavily affect food consumption patterns. Therefore, there has been a surge in research funding for developing products and methods that offer safe, nutritionally balanced, and delightful food options. 3D food printing could be a creative solution for such requirements. While multiple challenges must be addressed, the technology promises waste minimization and the scope for on-site on-demand food preparation. This article begins with fundamental concepts of this subject, provides a timeline of the advancements in the field, and details the futuristic prospects of the technology for long-duration space missions.
    Keywords:  3D printing; Diet; Food customization; Food printing; Microgravity; Space foods
  19. Tissue Eng Part A. 2024 Jan 24.
      Millions of people suffer from tracheal defect worldwide each year, while autograft and allograft cannot meet existing treatment needs. Tissue-engineered trachea substitutes represent a promising treatment for tracheal defect, while lack of precisely personalize treatment abilities. Therefore, development of an artificial trachea that can be used for personalized transplantation is highly desired. Here, we reported the design and fabrication of an artificial trachea based on sericin microsphere by microtissue engineering technology and 3D printing for personalized repair of tracheal defect. The sericin microsphere possessed natural cell adhesion and promoting cell proliferation ability. Then, the microtissue was fabricated by co-incubation of sericin microspheres with chondrocytes and tracheal epithelial cells. This microtissue displayed good cytocompatibility and could support seed cells adhesion and proliferation. After that, this microtissue was individually assembled to form an artificial trachea by 3D printing. Notably, artificial trachea had an encouraging complete cartilaginous and epithelial structure after transplantation. Furthermore, the artificial trachea molecularly resembled native trachea as evidenced by similar expression of trachea-critical genes. Together, the work demonstrates the effectiveness of microtissue engineering and 3D printing for individual construction of artificial trachea, providing a promising approach for personalized treatment of tracheal defect.
  20. Adv Healthc Mater. 2024 Jan 25. e2303772
      Three-dimensional (3D) stem cell spheroids have immense potential for various tissue engineering applications. However, current spheroid fabrication techniques encounter cell viability issues due to limited oxygen access for cells trapped within the core, as well as non-specific differentiation issues due to the complicated environment following transplantation. In this study, we developed functional 3D spheroids using mesenchymal stem cells (MSCs) with two-dimensional (2D) hetero-nanostructures (HNS) composed of single-stranded DNA (ssDNA) binding carbon nanotubes (sdCNT) and gelatin-bind black phosphorus nanosheets (gBPNS). An osteogenic molecule, dexamethasone (DEX), was further loaded to fabricate an sdCNTgBP-DEX hetero-nanostructure. This approach aimed to establish a multi-functional cell-inductive 3D spheroid with improved oxygen transportation through hollow nanotubes, stimulated stem cell growth by phosphate ions supplied from BP oxidation, in-situ immunoregulation, and osteogenesis induction by DEX molecules after implantation. Initial transplantation of the 3D spheroids in rat calvarial bone defect showed in vivo macrophage shifts to an M2 phenotype, leading to a pro-healing microenvironment for regeneration. Prolonged implantation demonstrated outstanding in vivo neovascularization, osteointegration, and new bone regeneration. Therefore, these engineered 3D spheroids hold great promise for bone repair as they allow for stem cell delivery and provide immunoregulative and osteogenic signals within an all-in-one construct. This article is protected by copyright. All rights reserved.
    Keywords:  bone repair; hetero-nanostructures (HNS); immunomodulation; stem cell spheroids; two-dimensional materials