bims-biprem Biomed News
on Bioprinting for regenerative medicine
Issue of 2024‒01‒21
sixteen papers selected by
Seerat Maqsood, University of Teramo

  1. Semin Pediatr Surg. 2024 Jan 04. pii: S1055-8586(24)00006-4. [Epub ahead of print]33(1): 151385
      Pediatric surgery presents a unique challenge, requiring a specialized approach due to the intricacies of compact anatomy and the presence of distinct congenital features in young patients. Surgeons are tasked with making decisions that not only address immediate concerns but also consider the evolving needs of children as they grow. The advent of three-dimensional (3D) printing has emerged as a valuable tool to facilitate a personalized medical approach. This paper starts by outlining the basics of 3D modeling and printing. We then delve into the transformative role of 3D printing in pediatric surgery, elucidating its applications, benefits, and challenges. The paper concludes by envisioning the future prospects of 3D printing, foreseeing advancements in personalized treatment approaches, improved patient outcomes, and the continued evolution of this technology as an indispensable asset in the pediatric surgical arena.
    Keywords:  3D printing; Additive manufacturing; Emerging technology; Pediatric surgery; Personalized medicine; Simulation
  2. Int J Biol Macromol. 2024 Jan 14. pii: S0141-8130(24)00246-0. [Epub ahead of print] 129443
      3D bioprinting has emerged as a viable tool to fabricate 3D tissue constructs with high precision using various bioinks which offer instantaneous gelation, shape fidelity, and cytocompatibility. Among various bioinks, cellulose is the most abundantly available natural polymer & widely used as bioink for 3D bioprinting applications. To mitigate the demanding crosslinking needs of cellulose, it is frequently chemically modified or blended with other polymers to develop stable hydrogels. In this study, we have developed a thermoresponsive, composite bioink using carboxymethyl cellulose (CMC) and agarose in different ratios (9:1, 8:2, 7:3, 6:4, and 5:5). Among the tested combinations, the 5:5 ratio showed better gel formation at 37 °C and were further characterized for physico-chemical properties. Cytocompatibility was assessed by indirect cytotoxicity assay (ISO 10993-5) using skin fibroblasts cells. CMC-agarose (5:5) bioink was successfully used to fabricate complex 3D structures through extrusion bioprinting and maintained over 80 % cell viability over seven days. Finally, in vivo studies using rat full-thickness wounds showed the potential of CMC-agarose bulk and bioprinted gels in promoting skin regeneration. These results indicate the cytocompatibility and suitability of CMC-agarose bioinks for tissue engineering and 3D bioprinting applications.
    Keywords:  3D bioprinting; Agarose; Carboxymethyl cellulose; Cytocompatible; Hydrogels; Thermoresponsive
  3. Mater Today Bio. 2024 Feb;24 100924
      Three-dimensional (3D) bioprinting offers an automated, customizable solution to manufacture highly detailed 3D tissue constructs and holds great promise for regenerative medicine to solve the severe global shortage of donor tissues and organs. However, uni-material 3D bioprinting is not sufficient for manufacturing heterogenous 3D constructs with native-like microstructures and thus, innovative multi-material solutions are required. Here, we developed a novel multi-material 3D bioprinting strategy for bioprinting human corneal stroma. The human cornea is the transparent outer layer of your eye, and vision loss due to corneal blindness has serious effects on the quality of life of individuals. One of the main reasons for corneal blindness is the damage in the detailed organization of the corneal stroma where collagen fibrils are arranged in layers perpendicular to each other and the corneal stromal cells grow along the fibrils. Donor corneas for treating corneal blindness are scarce, and the current tissue engineering (TE) technologies cannot produce artificial corneas with the complex microstructure of native corneal stroma. To address this, we developed a novel multi-material 3D bioprinting strategy to mimic detailed organization of corneal stroma. These multi-material 3D structures with heterogenous design were bioprinted by using human adipose tissue -derived stem cells (hASCs) and hyaluronic acid (HA) -based bioinks with varying stiffnesses. In our novel design of 3D models, acellular stiffer HA-bioink and cell-laden softer HA-bioink were printed in alternating filaments, and the filaments were printed perpendicularly in alternating layers. The multi-material bioprinting strategy was applied for the first time in corneal stroma 3D bioprinting to mimic the native microstructure. As a result, the soft bioink promoted cellular growth and tissue formation of hASCs in the multi-material 3D bioprinted composites, whereas the stiff bioink provided mechanical support as well as guidance of cellular organization upon culture. Interestingly, cellular growth and tissue formation altered the mechanical properties of the bioprinted composite constructs significantly. Importantly, the bioprinted composite structures showed good integration to the host tissue in ex vivo cornea organ culture model. As a conclusion, the developed multi-material bioprinting strategy provides great potential as a biofabrication solution for manufacturing organized, heterogenous microstructures of native tissues. To the best of our knowledge, this multi-material bioprinting strategy has never been applied in corneal bioprinting. Therefore, our work advances the technological achievements in additive manufacturing and brings the field of corneal TE to a new level.
    Keywords:  3D bioprinting; Cornea; Heterogenous design; Human stem cells; Multi-material bioprinting
  4. Biofabrication. 2024 Jan 15.
      The existing 3D printing methods exhibit certain fabrication-dependent limitations for printing curved constructs that are relevant for many tissues. Four-dimensional (4D) printing is an emerging technology that is expected to revolutionize the field of tissue engineering and regenerative medicine (TERM). 4D printing is based on 3D printing, featuring the introduction of time as the fourth dimension, in which there is a transition from a 3D printed scaffold to a new, distinct, and stable state, upon the application of one or more stimuli. Here, we present an overview of the current developments of the 4D printing technology for TERM, with a focus on approaches to achieve temporal changes of the shape of the printed constructs that would enable biofabrication of highly complex structures. To this aim, the printing methods, types of stimuli, shape-shifting mechanisms, and cell-incorporation strategies are critically reviewed. Furthermore, the challenges of this very recent biofabrication technology as well as the future research directions are discussed. Our findings show that the most common printing methods so far are stereolithography (SLA) and extrusion bioprinting, followed by fused deposition modelling (FDM), while the shape-shifting mechanisms used for TERM applications are shape-memory and differential swelling for 4D printing and 4D bioprinting, respectively. For shape-memory mechanism, there is a high prevalence of synthetic materials, such as polylactic acid (PLA), poly(glycerol dodecanoate) acrylate (PGDA), or polyurethanes. On the other hand, different acrylate combinations of alginate, hyaluronan, or gelatin have been used for differential swelling-based 4D transformations. TERM applications include bone, vascular, and cardiac tissues as the main target of the 4D (bio)printing technology. The field has great potential for further development by considering the combination of multiple stimuli, the use of a wider range of 4D techniques, and the implementation of computational-assisted strategies.
    Keywords:  3D printing; 4D printing; regenerative medicine; shape-change transformation; shape-shifting; smart materials; stimuli-responsive
  5. Expert Opin Drug Deliv. 2024 Jan 18.
      INTRODUCTION: The Food and Drug Administration's approval of the first three-dimensional (3D) printed tablet, Spritam®, led to a burgeoning interest in using 3D printing to fabricate numerous drug delivery systems for different routes of administration. The high degree of manufacturing flexibility achieved through 3D printing facilitates the preparation of dosage forms with many actives with complex and tailored release profiles that can address individual patient needs.AREAS COVERED: This comprehensive review provides an in-depth look into the several 3D printing technologies currently utilized in pharmaceutical research. Additionally, the review delves into vaginal anatomy and physiology, 3D-printed drug delivery systems for vaginal applications, the latest research studies, and the challenges of 3D printing technology and future possibilities.
    EXPERT OPINION: 3D printing technology can produce drug-delivery devices or implants optimized for vaginal applications, including vaginal rings, intra-vaginal inserts, or biodegradable microdevices loaded with drugs, all custom-tailored to deliver specific medications with controlled release profiles. However, though the potential of 3D printing in vaginal drug delivery is promising, there are still challenges and regulatory hurdles to overcome before these technologies can be widely adopted and approved for clinical use. Extensive research and testing are necessary to ensure safety, effectiveness, and biocompatibility.
    Keywords:  3D printing; Extrusion-based deposition; Inkjet printing; Laser-based printing; Vaginal drug delivery
  6. Polymers (Basel). 2023 Nov 21. pii: 4470. [Epub ahead of print]15(23):
      Three-dimensional (3D) printing is a promising manufacturing platform in biomedical engineering. It offers significant advantages in fabricating complex and customized biomedical products with accuracy, efficiency, cost-effectiveness, and reproducibility. The rapidly growing field of three-dimensional printing (3DP), which emphasizes customization as its key advantage, is actively searching for functional materials. Among these materials, piezoelectric materials are highly desired due to their linear electromechanical and thermoelectric properties. Polymer piezoelectrics and their composites are in high demand as biomaterials due to their controllable and reproducible piezoelectric properties. Three-dimensional printable piezoelectric materials have opened new possibilities for integration into biomedical fields such as sensors for healthcare monitoring, controlled drug delivery systems, tissue engineering, microfluidic, and artificial muscle actuators. Overall, this review paper provides insights into the fundamentals of polymer piezoelectric materials, the application of polymer piezoelectric materials in biomedical fields, and highlights the challenges and opportunities in realizing their full potential for functional applications. By addressing these challenges, integrating 3DP and piezoelectric materials can lead to the development of advanced sensors and devices with enhanced performance and customization capabilities for biomedical applications.
    Keywords:  3D printing; biomedical applications; polymer piezoelectric materials; tissue engineering
  7. Tissue Cell. 2024 Jan 05. pii: S0040-8166(24)00005-3. [Epub ahead of print]87 102304
      Blood vessels are the tubes through which blood flows and are divided into three types: millimeter-scale arteries, veins, and capillaries as well as micrometer-scale capillaries. Arteries and veins are the conduits that carry blood, while capillaries are where blood exchanges substances with tissues. Blood vessels are mainly composed of collagen fibers, elastic fibers, glycosaminoglycans and other macromolecular substances. There are about 19 feet of blood vessels per square inch of skin in the human body, which shows how important blood vessels are to the human body. Because cardiovascular disease and vascular trauma are common in the population, a great number of researches have been carried out in recent years by simulating the structures and functions of the person's own blood vessels to create different levels of tissue-engineered blood vessels that can replace damaged blood vessels in the human body. However, due to the lack of effective oxygen and nutrient delivery mechanisms, these tissue-engineered vessels have not been used clinically. Therefore, in order to achieve better vascularization of engineered vascular tissue, researchers have widely explored the design methods of vascular systems of various sizes. In the near future, these carefully designed and constructed tissue engineered blood vessels are expected to have practical clinical applications. Exploring how to form multi-scale vascular networks and improve their compatibility with the host vascular system will be very beneficial in achieving this goal. Among them, 3D printing has the advantages of high precision and design flexibility, and the decellularized matrix retains active ingredients such as collagen, elastin, and glycosaminoglycan, while removing the immunogenic substance DNA. In this review, technologies and advances in 3D printing and decellularization-based artificial blood vessel manufacturing methods are systematically discussed. Recent examples of vascular systems designed are introduced in details, the main problems and challenges in the clinical application of vascular tissue restriction are discussed and pointed out, and the future development trends in the field of tissue engineered blood vessels are also prospected.
    Keywords:  3D printing; Artificial blood vessels; Biomaterials; Decellularization; Tissue engineering
  8. Trends Biotechnol. 2024 Jan 17. pii: S0167-7799(23)00323-2. [Epub ahead of print]
      3D printing technologies have the potential to revolutionize the manufacture of heart valves through the ability to create bespoke, complex constructs. In light of recent technological advances, we review the progress made towards 3D printing of heart valves, focusing on studies that have utilised these technologies beyond manufacturing patient-specific moulds. We first overview the key requirements of a heart valve to assess functionality. We then present the 3D printing technologies used to engineer heart valves. By referencing International Organisation for Standardisation (ISO) Standard 5840 (Cardiovascular implants - Cardiac valve prostheses), we provide insight into the achieved functionality of these valves. Overall, 3D printing promises to have a significant positive impact on the creation of artificial heart valves and potentially unlock full complex functionality.
    Keywords:  3D printing; additive manufacturing; heart valves; polymeric heart valves; tissue-engineered heart valves
  9. Biomed Pharmacother. 2024 Jan 16. pii: S0753-3322(24)00049-0. [Epub ahead of print]171 116168
      In patients with diabetic wounds, wound healing is impaired due to the presence of persistent oxidative stress, an altered inflammatory response, and impaired angiogenesis and epithelization. Salvianolic acid B (SAB), which is derived from the Chinese medicinal plant Salvia miltiorrhiza, has been found to exhibit antioxidant, anti-inflammatory, and proangiogenic effects. Previous studies have used 3D bioprinting technology incorporating sodium alginate (SA) and gelatin (Gel) as basic biomaterials to successfully produce artificial skin. In the current study, 3D bioprinting technology was used to incorporate SAB into SA-Gel to form a novel SAB-SA-Gel composite porous scaffold. The morphological characteristics, physicochemical characteristics, biocompatibility, and SAB release profile of the SAB-SA-Gel scaffolds were evaluated in vitro. In addition, the antioxidant, anti-inflammatory, and proangiogenic abilities of the SAB-SA-Gel scaffolds were evaluated in cells and in a rat model. Analysis demonstrated that 1.0 wt% (the percentage of SAB in the total weight of the solution containing SA and Gel) SAB-SA-Gel scaffolds had strong antioxidant, anti-inflammatory, and proangiogenic properties both in cells and in the rat model. The 1.0% SAB-SA-Gel scaffold reduced the expression of tumor necrosis factor-α, interleukin-6, and interluekin-1β and increased the expression of transforming growth factor-β. In addition, this scaffold removed excessive reactive oxygen species by increasing the expression of superoxide dismutase, thereby protecting fibroblasts from injury. The scaffold increased the expression of vascular endothelial growth factor and platelet/endothelial cell adhesion molecule-1, accelerated granulation tissue regeneration and collagen deposition, and promoted wound healing. These findings suggest that this innovative scaffold may have promise as a simple and efficient approach to managing diabetic wound repair.
    Keywords:  3D bioprinting; Diabetes; Salvianolic acid B; Skin scaffold; Wound
  10. Mater Today Bio. 2024 Feb;24 100929
      The immune microenvironment plays a pivotal role in osteoanagenesis. Biomaterials can modulate osteogenic efficacy by inducing specific local immune reactions. As 3D-printing technology advances, digital light projection printing has emerged as a promising method for creating large scale, high-precision biomaterial scaffolds. By adjusting the solid content and the sintering conditions during printing, the pore size of biomaterials can be meticulously controlled. Yet, the systematic influence of pore size on the immune microenvironment remains uncharted. We fabricated 3D-printed hydroxyapatite bioceramic scaffolds with three distinct pore sizes: 400 μm, 600 μm, and 800 μm. Our study revealed that scaffolds with a pore size of 600 μm promote macrophage M2 polarization, which is achieved by upregulating interferon-beta and HIF-1α production. When these materials were implanted subcutaneously in rats and within rabbit skulls, we observed that the 600 μm scaffolds notably improved the long-term inflammatory response, fostered vascular proliferation, and augmented new bone growth. This research paves the way for innovative therapeutic strategies for treating large segmental bone defects in clinical settings.
    Keywords:  3D printing technology; Bone regeneration; Digital light projection; Immunological environment; Pore size
  11. Mol Pharm. 2024 Jan 18.
      Electrospinning has become a widely used and efficient method for manufacturing nanofibers from diverse polymers. This study introduces an advanced electrospinning technique, Xspin - a multi-functional 3D printing platform coupled with electrospinning system, integrating a customised 3D printhead, MaGIC - Multi-channeled and Guided Inner Controlling printheads. The Xspin system represents a cutting-edge fusion of electrospinning and 3D printing technologies within the realm of pharmaceutical sciences and biomaterials. This innovative platform excels in the production of novel fiber with various materials and allows for the creation of highly customized fiber structures, a capability hitherto unattainable through conventional electrospinning methodologies. By integrating the benefits of electrospinning with the precision of 3D printing, the Xspin system offers enhanced control over the scaffold morphology and drug release kinetics. Herein, we fabricated a model floating pharmaceutical dosage for the dual delivery of curcumin and ritonavir and thoroughly characterized the product. Fourier transform infrared (FTIR) spectroscopy demonstrated that curcumin chemically reacted with the polymer during the Xspin process. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the solid-state properties of the active pharmaceutical ingredient after Xspin processing. Scanning electron microscopy (SEM) revealed the surface morphology of the Xspin-produced fibers, confirming the presence of the bifiber structure. To optimize the quality and diameter control of the electrospun fibers, a design of experiment (DoE) approach based on quality by design (QbD) principles was utilized. The bifibers expanded to approximately 10-11 times their original size after freeze-drying and effectively entrapped 87% curcumin and 84% ritonavir. In vitro release studies demonstrated that the Xspin system released 35% more ritonavir than traditional pharmaceutical pills in 2 h, with curcumin showing complete release in pH 1.2 in 5 min, simulating stomach media. Furthermore, the absorption rate of curcumin was controlled by the characteristics of the linked polymer, which enables both drugs to be absorbed at the desired time. Additionally, multivariate statistical analyses (ANOVA, pareto chart, etc.) were conducted to gain better insights and understanding of the results such as discern statistical differences among the studied groups. Overall, the Xspin system shows significant potential for manufacturing nanofiber pharmaceutical dosages with precise drug release capabilities, offering new opportunities for controlled drug delivery applications.
    Keywords:  3D printing; DoE; biaxial nano/microfibers; controlled drug delivery; electrospinning; floating pharmaceutical scaffolds
  12. Polymers (Basel). 2023 Nov 21. pii: 4473. [Epub ahead of print]15(23):
      Three-dimensional bioprinting represents an innovative platform for fabricating intricate, three-dimensional (3D) tissue structures that closely resemble natural tissues. The development of hybrid bioinks is an actionable strategy for integrating desirable characteristics of components. In this study, cellulose recovered from plum seed was processed to synthesize carboxymethyl cellulose (CMC) for 3D bioprinting. The plum seeds were initially subjected to α-cellulose recovery, followed by the synthesis and characterization of plum seed-derived carboxymethyl cellulose (PCMC). Then, hybrid bioinks composed of PCMC and sodium alginate were fabricated, and their suitability for extrusion-based bioprinting was explored. The PCMC bioinks exhibit a remarkable shear-thinning property, enabling effortless extrusion through the nozzle and maintaining excellent initial shape fidelity. This bioink was then used to print muscle-mimetic 3D structures containing C2C12 cells. Subsequently, the cytotoxicity of PCMC was evaluated at different concentrations to determine the maximum acceptable concentration. As a result, cytotoxicity was not observed in hydrogels containing a suitable concentration of PCMC. Cell viability was also evaluated after printing PCMC-containing bioinks, and it was observed that the bioprinting process caused minimal damage to the cells. This suggests that PCMC/alginate hybrid bioink can be used as a very attractive material for bioprinting applications.
    Keywords:  bioink; bioprinting; carboxymethyl cellulose; plum seed-derived carboxymethyl cellulose
  13. J Biomed Sci. 2024 Jan 14. 31(1): 7
      Three-dimensional (3D) cell cultures have emerged as valuable tools in cancer research, offering significant advantages over traditional two-dimensional (2D) cell culture systems. In 3D cell cultures, cancer cells are grown in an environment that more closely mimics the 3D architecture and complexity of in vivo tumors. This approach has revolutionized cancer research by providing a more accurate representation of the tumor microenvironment (TME) and enabling the study of tumor behavior and response to therapies in a more physiologically relevant context. One of the key benefits of 3D cell culture in cancer research is the ability to recapitulate the complex interactions between cancer cells and their surrounding stroma. Tumors consist not only of cancer cells but also various other cell types, including stromal cells, immune cells, and blood vessels. These models bridge traditional 2D cell cultures and animal models, offering a cost-effective, scalable, and ethical alternative for preclinical research. As the field advances, 3D cell cultures are poised to play a pivotal role in understanding cancer biology and accelerating the development of effective anticancer therapies. This review article highlights the key advantages of 3D cell cultures, progress in the most common scaffold-based culturing techniques, pertinent literature on their applications in cancer research, and the ongoing challenges.
    Keywords:  Decellularized tissues; Extracellular matrix (ECM); Hydrogels; Microfluidics; Scaffolds; Three-dimensional (3D) cell culture
  14. Int J Biol Macromol. 2024 Jan 13. pii: S0141-8130(24)00210-1. [Epub ahead of print] 129407
      The utilization of 3D printing has become increasingly common in the construction of composite scaffolds. In this study, magnetic mesoporous bioactive glass (MMBG) was incorporated into polyhydroxybutyrate (PHB) to construct extrusion-based 3D printed scaffold. After fabrication of the PHB/MMBG composite scaffolds, they were coated with chitosan (Cs) and chitosan/multi-walled carbon nanotubes (Cs/MWCNTs) solutions utilizing deep coating method. FTIR was conducted to confirm the presence of Cs and MWCNTs on the scaffolds' surface. The findings of mechanical analysis illustrated that presence of Cs/MWCNTs on the composite scaffolds increases compressive young modulus significantly, from 16.5 to 42.2 MPa. According to hydrophilicity evaluation, not only MMBG led to decrease the contact angle of pure PHB but also scaffolds surface modification utilization of Cs and MWCNTs, the contact angle decreased significantly from 82.34° to 54.15°. Furthermore, investigation of cell viability, cell metabolism and inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β) proved that the scaffolds not only do not stimulate the immune system, but also polarize macrophage cells from M1 phase to M2 phase. The present study highlights the suitability of 3D printed scaffold PHB/MMBG with Cs/MWCNTs coating for bone tissue engineering.
    Keywords:  3D printing; Bone regeneration; Chitosan; Magnetic mesoporous bioactive glass; Multiwalled carbon nanotubes; Poly 3-hydroxybutyrate
  15. Biomater Adv. 2024 Jan 08. pii: S2772-9508(24)00003-7. [Epub ahead of print]158 213760
      The utilization of 3D printing technology for the fabrication of graft substitutes in bone repair holds immense promise. However, meeting the requirements for printability, bioactivity, mechanical strength, and biological properties of 3D printed structures concurrently poses a significant challenge. In this study, we introduce a novel approach by incorporating amorphous magnesium phosphate-graphene oxide (AMP-GO) into a thermo-crosslinkable chitosan/β glycerol phosphate (CS/GP) ink. We fabricated thermo-crosslinkable CS inks containing varying concentrations (10 %, 20 %, or 30 % weight) of AMP-GO. The 3D printed scaffolds incorporating 20 % AMP-GO exhibited significantly improved mechanical properties, with compressive strengths of 4.5 ± 0.06 MPa compared to 0.5 ± 0.03 MPa for CS printed scaffolds. Moreover, the CS/AMP-GO inks demonstrated enhanced antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria, attributed to the release of magnesium cations and the performance of GO. Additionally, CS/20AMP-GO ink facilitated increased adhesion, viability, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs), as evidenced by the upregulation of ALP, COL1, and Runx2 expression, which were elevated 9.8, 6.5, and >22 times, respectively, compared to pure CS scaffolds. Considering its exceptional in vivo osteogenic potential, we anticipate that the CS/20AMP-GO ink holds great potential for 3D printing of bone grafts.
    Keywords:  3D printing; Amorphous magnesium phosphate; Bone tissue engineering; Chitosan; Graphene oxide
  16. Mater Today Bio. 2024 Feb;24 100918
      The development of skin substitutes aims to replace, mimic, or improve the functions of human skin, regenerate damaged skin tissue, and replace or enhance skin function. This includes artificial skin, scaffolds or devices designed for treatment, imitation, or improvement of skin function in wounds and injuries. Therefore, tremendous efforts have been made to develop functional skin substitutes. However, there is still few reports systematically discuss the relationship between the advanced function and design requirements. In this paper, we review the classification, functions, and design requirements of artificial skin or skin substitutes. Different manufacturing strategies for skin substitutes such as hydrogels, 3D/4D printing, electrospinning, microfluidics are summarized. This review also introduces currently available skin substitutes in clinical trials and on the market and the related regulatory requirements. Finally, the prospects and challenges of skin substitutes in the field of tissue engineering are discussed.
    Keywords:  Artificial skin; Design strategy; Manufacturing methods; Skin regeneration; Skin substitutes