bims-biprem 2024-12-15 papers

bims-biprem

Biomed News

on Bioprinting for regenerative medicine

Issue of 2024–12–15
eleven papers selected by
Seerat Maqsood, University of Teramo

Droplet-based 3D bioprinting for drug delivery and screening.
Integrating 3D Bioprinting and Organoids to Better Recapitulate the Complexity of Cellular Microenvironments for Tissue Engineering.
AI-driven 3D bioprinting for regenerative medicine: From bench to bedside.
Innovative Applications of Nanocellulose in 3D Printing: A Review.
Advances in additive manufacturing for bone tissue engineering: materials, design strategies, and applications.
Trends and advances in silk based 3D printing/bioprinting towards cartilage tissue engineering and regeneration.
3D-Bioprinting for Precision Microtissue Engineering: Advances, Applications, and Prospects.
3D Printed GelMA/CHIMA Cross-Linked Network Hydrogel for Angiogenesis.
Advancing tumor microenvironment and lymphoid tissue research through 3D bioprinting and biofabrication.
3D printed magnetoactive nanocomposite scaffolds for bone regeneration.
A quercetin nanoparticle combined with a 3D-printed decellularized extracellular matrix/ gelatin methacryloyl/sodium alginate biomimetic tumor model for the treatment of melanoma.

Adv Drug Deliv Rev. 2024 Dec 10. pii: S0169-409X(24)00308-9. [Epub ahead of print] 115486

Droplet-based 3D bioprinting for drug delivery and screening.

Heqi Xu, Shaokun Zhang, Kaidong Song, Huayong Yang, Jun Yin, Yong Huang.

  Recently, the conventional criterion of "one-size-fits-all" is not qualified for each individual patient, requiring precision medicine for enhanced therapeutic effects. Besides, drug screening is a high-cost and time-consuming process which requires innovative approaches to facilitate drug development rate. Benefiting from consistent technical advances in 3D bioprinting techniques, droplet-based 3D bioprinting techniques have been broadly utilized in pharmaceutics due to the noncontact printing mechanism and precise control on the deposition position of droplets. More specifically, cell-free/cell-laden bioinks which are deposited for the fabrication of drug carriers/3D tissue constructs have been broadly utilized for precise drug delivery and high throughput drug screening, respectively. This review summarizes the mechanism of various droplet-based 3D bioprinting techniques and the most up-to-date applications in drug delivery and screening and discusses the potential improvements of droplet-based 3D bioprinting techniques from both technical and material aspects. Through technical innovations, materials development, and the assistance from artificial intelligence, the formation process of drug carriers will be more stable and accurately controlled guaranteeing precise drug delivery. Meanwhile, the shape fidelity and uniformity of the printed tissue models will be significantly improved ensuring drug screening efficiency and efficacy.

Keywords:  Droplet-based 3D bioprinting; Drug carriers; Drug delivery; Drug screening; Inkjet 3D bioprinting; Personalized medicine; Tissue models

DOI:  https://doi.org/10.1016/j.addr.2024.115486
Adv Healthc Mater. 2024 Dec 08. e2403762

Integrating 3D Bioprinting and Organoids to Better Recapitulate the Complexity of Cellular Microenvironments for Tissue Engineering.

Yan Hu, Tong Zhu, Haitao Cui, Haijun Cui.

  Organoids, with their capacity to mimic the structures and functions of human organs, have gained significant attention for simulating human pathophysiology and have been extensively investigated in the recent past. Additionally, 3D bioprinting, as an emerging bio-additive manufacturing technology, offers the potential for constructing heterogeneous cellular microenvironments, thereby promoting advancements in organoid research. In this review, the latest developments in 3D bioprinting technologies aimed at enhancing organoid engineering are introduced. The commonly used bioprinting methods and materials for organoids, with a particular emphasis on the potential advantages of combining 3D bioprinting with organoids are summarized. These advantages include achieving high cell concentrations to form large cellular aggregates, precise deposition of building blocks to create organoids with complex structures and functions, and automation and high throughput to ensure reproducibility and standardization in organoid culture. Furthermore, this review provides an overview of relevant studies from recent years and discusses the current limitations and prospects for future development.

Keywords:  3D bioprinting; biofabrication; cellular microenvironments; organoids; tissue engineering

DOI:  https://doi.org/10.1002/adhm.202403762
Bioact Mater. 2025 Mar;45 201-230

AI-driven 3D bioprinting for regenerative medicine: From bench to bedside.

Zhenrui Zhang, Xianhao Zhou, Yongcong Fang, Zhuo Xiong, Ting Zhang.

  In recent decades, 3D bioprinting has garnered significant research attention due to its ability to manipulate biomaterials and cells to create complex structures precisely. However, due to technological and cost constraints, the clinical translation of 3D bioprinted products (BPPs) from bench to bedside has been hindered by challenges in terms of personalization of design and scaling up of production. Recently, the emerging applications of artificial intelligence (AI) technologies have significantly improved the performance of 3D bioprinting. However, the existing literature remains deficient in a methodological exploration of AI technologies' potential to overcome these challenges in advancing 3D bioprinting toward clinical application. This paper aims to present a systematic methodology for AI-driven 3D bioprinting, structured within the theoretical framework of Quality by Design (QbD). This paper commences by introducing the QbD theory into 3D bioprinting, followed by summarizing the technology roadmap of AI integration in 3D bioprinting, including multi-scale and multi-modal sensing, data-driven design, and in-line process control. This paper further describes specific AI applications in 3D bioprinting's key elements, including bioink formulation, model structure, printing process, and function regulation. Finally, the paper discusses current prospects and challenges associated with AI technologies to further advance the clinical translation of 3D bioprinting.

Keywords:  3D bioprinting; Artificial intelligence; Clinical translation; Machine learning; Quality by design; Regenerative medicine

DOI:  https://doi.org/10.1016/j.bioactmat.2024.11.021
Small. 2024 Dec 10. e2407956

Innovative Applications of Nanocellulose in 3D Printing: A Review.

Yuqi Tong, Chuang Jiang, Chuye Ji, Wei Liu, Yixiang Wang.

  Cellulose nanofibrils (CNFs) and cellulose nanocrystals (CNCs) are nanoscale materials with unique mechanical properties and geometry that attract considerable interest in recent years for a wide range of applications. This review pays special attention to the recent progress of CNFs and CNCs assisted 3D printing in medicine, food, engineering, and architecture fields. Various types of CNFs and CNCs used for 3D printing are summarized. The addition of nanocellulose improves the printability and quality of printed objects in certain cases, leading to greater accuracy and durability. The created functional structures with specific properties have promising applications in various fields such as medicine and food preservation and viscosity enhancement. Finally, this work highlights the transformative potential of nanocellulose-assisted 3D printing to revolutionize a range of fields and the need for continued research and development to overcome current technical challenges.

Keywords:  3D printing; applications; cellulose nanocrystals; cellulose nanofibrils; ink properties; raw materials

DOI:  https://doi.org/10.1002/smll.202407956
Biomed Mater. 2024 Dec 11.

Advances in additive manufacturing for bone tissue engineering: materials, design strategies, and applications.

Ribin Varghese Pazhamannil, Mohammad Alkhedher.

  The growing annual demand for bone grafts and artificial implants emphasizes the need for effective solutions to repair or replace injured bones. Additive manufacturing technology offers unique merits for advancing bone tissue engineering (BTE), enabling the creation of scaffolds and implants with customized shapes and designs, interconnected architecture, controlled mechanical properties and compositions, and broadening its range of applications. It overcomes the limitations of traditional manufacturing methods such as electrospinning, salt leaching, freeze drying, solvent casting etc. This review highlights additive manufacturing technologies and their applications in BTE, as well as materials and scaffold architectures to widen the potential of the biomedical sector. The selection of optimal printing methods for BTE requires careful consideration of the advantages and disadvantages against the needs for degradation, strength, and biocompatibility. Material extrusion and powder bed fusion techniques are the most widely used additive manufacturing processes in BTE. The comprehensive review also revealed that parametric designs such as Triply Periodic Minimal Surface (TPMS) and Voronoi hold better characteristics for their application in BTE. Voronoi designs exhibit exceptional randomness whereas TPMS structures feature high permeability with continuous surfaces. Topology optimized and gradient models exhibited superior physical and mechanical properties compared to uniform lattices. Future research should focus on the development of novel biomaterials, multi-material printing, assessing long-term impacts, and enhancing 3D printing technologies.

Keywords:  3D Bioprinting; Additive Manufacturing; Biomaterials; Bone Tissue Engineering; Mechanical Properties; TPMS; Topology Optimization

DOI:  https://doi.org/10.1088/1748-605X/ad9dce
Prog Biomed Eng (Bristol). 2024 Mar 21. 6(2):

Trends and advances in silk based 3D printing/bioprinting towards cartilage tissue engineering and regeneration.

Yogendra Pratap Singh, Ashutosh Bandyopadhyay, Souradeep Dey, Nandana Bhardwaj, Biman B Mandal.

  Cartilage repair remains a significant clinical challenge in orthopedics due to its limited self- regeneration potential and often progresses to osteoarthritis which reduces the quality of life. 3D printing/bioprinting has received vast attention in biofabrication of functional tissue substitutes due to its ability to develop complex structures such as zonally structured cartilage and osteochondral tissue as per patient specifications with precise biomimetic control. Towards a suitable bioink development for 3D printing/bioprinting, silk fibroin has garnered much attention due to its advantageous characteristics such as shear thinning behavior, cytocompatibility, good printability, structural fidelity, affordability, and ease of availability and processing. This review attempts to provide an overview of current trends/strategies and recent advancements in utilizing silk-based bioinks/biomaterial-inks for cartilage bioprinting. Herein, the development of silk-based bioinks/biomaterial-inks, its components and the associated challenges, along with different bioprinting techniques have been elaborated and reviewed. Furthermore, the applications of silk-based bioinks/biomaterial-inks in cartilage repair followed by challenges and future directions are discussed towards its clinical translations and production of next-generation biological implants.

Keywords:  bioink; biomaterial ink; bioprinting; cartilage; silk fibroin; tissue engineering

DOI:  https://doi.org/10.1088/2516-1091/ad2d59
Adv Healthc Mater. 2024 Dec 08. e2403781

3D-Bioprinting for Precision Microtissue Engineering: Advances, Applications, and Prospects.

Jinrun Liu, Qi Wang, Yinpeng Le, Min Hu, Chen Li, Ni An, Qingru Song, Wenzhen Yin, Wenrui Ma, Mingyue Pan, Yutian Feng, Yunfang Wang, Lu Han, Juan Liu.

  Microtissues, engineered to emulate the complexity of human organs, are revolutionizing the fields of regenerative medicine, disease modelling, and drug screening. Despite the promise of traditional microtissue engineering, it has yet to achieve the precision required to fully replicate organ-like structures. Enter 3D bioprinting, a transformative approach that offers unparalleled control over the microtissue's spatial arrangement and mechanical properties. This cutting-edge technology enables the detailed layering of bioinks, crafting microtissues with tissue-like 3D structures. It allows for the direct construction of organoids and the fine-tuning of the mechanical forces vital for tissue maturation. Moreover, 3D-printed devices provide microtissues with the necessary guidance and microenvironments, facilitating sophisticated tissue interactions. The applications of 3D-printed microtissues are expanding rapidly, with successful demonstrations of their functionality in vitro and in vivo. This technology excels at replicating the intricate processes of tissue development, offering a more ethical and controlled alternative to traditional animal models. By simulating in vivo conditions, 3D-printed microtissues are emerging as powerful tools for personalized drug screening, offering new avenues for pharmaceutical development and precision medicine.

Keywords:  3D bioprinting; bioinks; drug screening; microtissue engineering; organoids

DOI:  https://doi.org/10.1002/adhm.202403781
Biotechnol Bioeng. 2024 Dec 11.

3D Printed GelMA/CHIMA Cross-Linked Network Hydrogel for Angiogenesis.

Zixian Liu, Meng Li, Rong Cheng, Lijing Wang, Peiyi Hou, Lu Han, Shengbo Sang.

  Vascularization is a key issue facing the construction of functional three-dimensional (3D) tissues, which is critical for the long-term survival and stability of tissue construct transplantation. In this study, a photocurable hydrogel material carboxymethyl chitosan (CHIMA) was successfully prepared and integrated with methacryloyl gelatin (GelMA) to construct the bioink GelMA/CHIMA, which was subsequently used 3D printing technology to prepared a bioactive scaffold with angiogenesis-inducing functionality. The results showed that the cross-linked GelMA/CHIMA bioink had a porous structure that supported cell growth and metabolism. The incorporation of CHIMA could significantly improve the hydrophilicity, swelling rate, pressure resistance and mechanical strength of the bioink. GelMA/CHIMA bioink supported the survival and continued proliferation of human umbilical vein endothelial cells (HUVECs) in the scaffold. In particular, the bioink composed of 8 wt% GelMA and 2 wt% CHIMA could stimulate the expression of angiogenesis genes. 3D printed bioactive scaffolds supported the survival of HUVECs and had abundant protein deposition including CD31 and VEGF. Therefore, this study constructed a bioactive scaffold with angiogenesis induction function, which provides a feasible strategy for the construction of vascularized complex tissues.

Keywords:  3D printing; CHIMA; GelMA; angiogenesis; bioink

DOI:  https://doi.org/10.1002/bit.28907
Adv Drug Deliv Rev. 2024 Dec 07. pii: S0169-409X(24)00307-7. [Epub ahead of print]217 115485

Advancing tumor microenvironment and lymphoid tissue research through 3D bioprinting and biofabrication.

Corrado Mazzaglia, Yan Yan Shery Huang, Jacqueline D Shields.

Cancer progression is significantly influenced by the complex interactions within the tumor microenvironment (TME). Immune cells, in particular, play a critical role by infiltrating tumors from the circulation and surrounding lymphoid tissues in an attempt to control their spread. However, they often fail in this task. Current in vivo and in vitro preclinical models struggle to fully capture these intricate interactions affecting our ability to understand immune evasion and predict drugs behaviour in the clinic. To address this challenge, biofabrication and particularly 3D bioprinting has emerged as a promising tool for modeling both tumors and the immune system. Its ability to incorporate multiple cell types into 3D matrices, enable tissue compartmentalization with high spatial accuracy, and integrate vasculature makes it a valuable approach. Nevertheless, limited research has focused on capturing the complex tumor-immune interplay in vitro. This review highlights the composition and significance of the TME, the architecture and function of lymphoid tissues, and innovative approaches to modeling their interactions in vitro, while proposing the concept of an extended TME.

DOI: https://doi.org/10.1016/j.addr.2024.115485
Biomed Mater. 2024 Dec 13.

3D printed magnetoactive nanocomposite scaffolds for bone regeneration.

Yeganeh Kaviani, Hossein Eslami, Mojtaba Ansari, Seyed Ali Poursamar.

  Simulating the natural cellular environment using magnetic stimuli could be a potential strategy to promote bone tissue regeneration. This study unveiled a novel 3D printed composite scaffold containing PCL (poly caprolactone) and CFF-NPs (cobalt ferrite/forsterite core-shell nanoparticles) to investigate physical, mechanical and biological properties of magnetoactive scaffold under static magnetic field. For this purpose, core-shell structure is synthesized through a two-step synthesis strategy in which cobalt ferrite nanoparticles are prepared via sol-gel combustion method and then are coated through sol-gel method with forsterite. The characterization regarding CFF-NPs reveals that Mg2SiO4-coated CoFe2O4 nanoparticles is successfully synthesized with a core-shell structure. Afterwards, CFF-NPs are embedded within the PCL with different percentages, ultimately 3D printed scaffolds were fabricated. The in vitro assessments demonstrated that the incorporated CFF-NPs are able to cause a decrease in contact angle which was responsible for modulating purposefully the degradation rate of PCL scaffold, resulting in providing the obligatory environment for bone growth. In addition, it was observed that scaffolds including PCL combined with CFF-NPs are susceptible to improve the mechanical performance of nanocomposite scaffolds, up to a certain concentration (50% CFF-NPs and 50% PCL) with compressive modulus of 42.5 MPa. Moreover, when being exposed to simulated body fluid (SBF) solution, hydroxyapatite deposition on the surface of scaffolds was observed. Thus, these compositions may be useful for improving the osteointegration between the implant and bone tissue after implantation. Finally, the simultaneous effect of magnetic nanoparticles and magnetic field of 125 mT evaluated on cellular behavior of scaffolds. The results showed that the cell viability of all groups under magnetic field were better than that for standard condition. Likewise, SEM images of cultured cells on scaffolds confirmed that the combined effect of these factors could be lead to promote better cell adhesion, dispersion, and bone regeneration.

Keywords:  3D printing; Bone regeneration; Cobalt ferrite; Magnetic nanocomposite; Polycaprolactone; core-shell; forsterite

DOI:  https://doi.org/10.1088/1748-605X/ad9f04
Int J Biol Macromol. 2024 Dec 11. pii: S0141-8130(24)09491-1. [Epub ahead of print] 138680

A quercetin nanoparticle combined with a 3D-printed decellularized extracellular matrix/ gelatin methacryloyl/sodium alginate biomimetic tumor model for the treatment of melanoma.

Huan Fang, Jie Xu, Hailin Ma, Zijiao Feng, Yuen Yee Cheng, Yi Nie, Yanchun Guan, Yaqian Liu, Kedong Song.

  The traditional drug efficacy testing often conducted using two-dimensional (2D) cell culture methods, which do not accurately replicate the complexity of the tumor microenvironment. Melanoma in particular, is known for its high incidence, and aggressive nature, highlighting the need for more sophisticated in vitro models that better simulate the tumor's true biological microenvironment drug research and therapy. In this study, we developed quercetin nanoparticles (QueNPs) with enhanced water solubility and promising tumor therapeutic effects. These nanoparticles were formed through the self-assembly of Pluronic F127 (PF127) and quercetin (Que). To better mimic the in vivo tumor environment, we also created a composite scaffold using three-dimensional (3D) printing technology, incorporating a decellularized extracellular matrix (dECM), which closely resembles the native tissue microenvironment. The scaffold also included gelatin methacryloyl (GelMA), which forms a polymeric network via photocrosslinking, and sodium alginate (SA), which enhances structural stability through ion cross-linking with calcium ions. This combination was used to construct a more physiologically relevant 3D melanoma model. The anti-cancer effects of QueNPs were assessed in both 2D and 3D culture systems. The results showed that tumor cells in the 3D model formed cluster and distributed across the scaffold, creating a more realistic tumor microenvironment compared to the 2D system. Cells in the 3D tumor model exhibited significant resistance to QueNPs, with a time dependent response that resulted in a killing rate of over 90 % by day 14. These findings highlight the efficiency of the QueNPs in the 3D melanoma model and emphasize the importance of incorporation 3D printing and nanomedicine for more accurate and effective drug screening.

Keywords:  Drug screening; In vitro melanoma model; Quercetin nanoparticles; Three-dimensional printing

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.138680