bims-biprem 2024-06-02 papers

bims-biprem

Biomed News

on Bioprinting for regenerative medicine

Issue of 2024–06–02
thirteen papers selected by
Seerat Maqsood, University of Teramo

Bioprinting salivary gland models and their regenerative applications.
A comprehensive review of the application of 3D-bioprinting in chronic wound management.
A 3D Bioprinted Cortical Organoid Platform for Modeling Human Brain Development.
3D bioprinting of dense cellular structures within hydrogels with spatially controlled heterogeneity.
Harnessing oriented arrangement of collagen fibers by 3D printing for enhancing mechanical and osteogenic properties of mineralized collagen scaffolds.
Navigating the Challenges of 3D Printing Personalized Medicine in Space Explorations: A Comprehensive Review.
3D bioprinting platform development for high-throughput cancer organoid models construction and drug evaluation.
3D-printed nanomedicines for cancer therapy.
Activating the healing process: three-dimensional culture of stem cells in Matrigel for tissue repair.
Advancing Bone Regeneration: Unveiling the Potential of 3D Cell Models in the Evaluation of Bone Regenerative Materials.
Brachytherapy and 3D printing for skin cancer: A review paper.
3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.
Development of a Three-Dimensional Multicellular Model of Human Neuroblastoma Using Matrigel as an Extracellular Matrix Analogue.

BDJ Open. 2024 May 30. 10(1): 39

Bioprinting salivary gland models and their regenerative applications.

Jutapak Klangprapan, Glauco R Souza, João N Ferreira.

OBJECTIVE: Salivary gland (SG) hypofunction is a common clinical condition arising from radiotherapy to suppress head and neck cancers. The radiation often destroys the SG secretory acini, and glands are left with limited regenerative potential. Due to the complex architecture of SG acini and ducts, three-dimensional (3D) bioprinting platforms have emerged to spatially define these in vitro epithelial units and develop mini-organs or organoids for regeneration. Due to the limited body of evidence, this comprehensive review highlights the advantages and challenges of bioprinting platforms for SG regeneration.
METHODS: SG microtissue engineering strategies such as magnetic 3D bioassembly of cells and microfluidic coaxial 3D bioprinting of cell-laden microfibers and microtubes have been proposed to replace the damaged acinar units, avoid the use of xenogeneic matrices (like Matrigel), and restore salivary flow.
RESULTS: Replacing the SG damaged organ is challenging due to its complex architecture, which combines a ductal network with acinar epithelial units to facilitate a unidirectional flow of saliva. Our research group was the first to develop 3D bioassembly SG epithelial functional organoids with innervation to respond to both cholinergic and adrenergic stimulation. More recently, microtissue engineering using coaxial 3D bioprinting of hydrogel microfibers and microtubes could also supported the formation of viable epithelial units. Both bioprinting approaches could overcome the need for Matrigel by facilitating the assembly of adult stem cells, such as human dental pulp stem cells, and primary SG cells into micro-sized 3D constructs able to produce their own matrix and self-organize into micro-modular tissue clusters with lumenized areas. Furthermore, extracellular vesicle (EV) therapies from organoid-derived secretome were also designed and validated ex vivo for SG regeneration after radiation damage.
CONCLUSION: Magnetic 3D bioassembly and microfluidic coaxial bioprinting platforms have the potential to create SG mini-organs for regenerative applications via organoid transplantation or organoid-derived EV therapies.

DOI: https://doi.org/10.1038/s41405-024-00219-2
Expert Opin Drug Deliv. 2024 May 29.

A comprehensive review of the application of 3D-bioprinting in chronic wound management.

Prathap Madeswara Guptha, Jovita Kanoujia, Ankita Kishore, Neha Raina, Abhishek Wahi, Piyush Kumar Gupta, Madhu Gupta.

   INTRODUCTION: Chronic wounds require more sophisticated care than standard wound care because they are becoming more severe as a result of diseases like diabetes. By resolving shortcomings in existing methods, 3D-bioprinting offers a viable path toward personalized, mechanically strong, and cell-stimulating wound dressings.
AREAS COVERED: This review highlights the drawbacks of traditional approaches while navigating the difficulties of managing chronic wounds. The conversation revolves around employing natural biomaterials for customized dressings, with a particular emphasis on 3D-bioprinting. A thorough understanding of the uses of 3D-printed dressings in a range of chronic wound scenarios is provided by insights into recent research and patents.
EXPERT OPINION: The expert view recognizes wounds as a historical human ailment and emphasizes the growing difficulties and expenses related to wound treatment. The expert acknowledges that 3D printing is revolutionary, but also points out that it is still in its infancy and has the potential to enhance mass production rather than replace it. The review highlights the benefits of 3D printing for wound dressings by providing instances of smart materials that improve treatment results by stimulating angiogenesis, reducing pain, and targeting particular enzymes. The expert advises taking action to convert the technology's prospective advantages into real benefits for patients, even in the face of resistance to change in the healthcare industry. It is believed that the increasing evidence from in-vivo studies is promising and represents a positive change in the treatment of chronic wounds toward sophisticated 3D-printed dressings.

Keywords:  3D-bioprinting; Chronic wounds; natural biomaterials; wound; wound dressing

DOI:  https://doi.org/10.1080/17425247.2024.2355184
Adv Healthc Mater. 2024 May 30. e2401603

A 3D Bioprinted Cortical Organoid Platform for Modeling Human Brain Development.

Melissa A Cadena, Anson Sing, Kylie Taylor, Linqi Jin, Liqun Ning, Mehdi Salar Amoli, Yamini Singh, The Brain Organoid Hub, Samantha N Lanjewar, Martin L Tomov, Vahid Serpooshan, Steven A Sloan.

  The ability to promote three-dimensional (3D) self-organization of induced pluripotent stem cells into complex tissue structures called organoids presents new opportunities for the field of developmental biology. Brain organoids have been used to investigate principles of neurodevelopment and neuropsychiatric disorders and serve as a drug screening and discovery platform. However, brain organoid cultures are currently limited by a lacking ability to precisely control their extracellular environment. Here, we employed 3D bioprinting to generate a high-throughput, tunable, and reproducible scaffold for controlling organoid development and patterning. Additionally, our approach supports the co-culture of organoids and vascular cells in a custom architecture containing interconnected endothelialized channels. Printing fidelity and mechanical assessments confirm that fabricated scaffolds closely match intended design features and exhibit stiffness values reflective of the developing human brain. Using organoid growth, viability, cytoarchitecture, proliferation, and transcriptomic benchmarks, we found that organoids cultured within the bioprinted scaffold long-term are healthy and have expected neuroectodermal differentiation. Lastly, we confirmed that the endothelial cells in printed channel structures can migrate towards and infiltrate into the embedded organoids. This work demonstrates a tunable 3D culturing platform that can be used to create more complex and accurate models of human brain development and underlying diseases. This article is protected by copyright. All rights reserved.

Keywords:  3D bioprinting; brain organoids; extracellular matrix; induced pluripotent stem cells; vasculature

DOI:  https://doi.org/10.1002/adhm.202401603
Biofabrication. 2024 May 31.

3D bioprinting of dense cellular structures within hydrogels with spatially controlled heterogeneity.

Alperen Abaci, Murat Guvendiren.

  Embedded bioprinting is an emerging technology for precise deposition of cell-laden or cell-only bioinks to construct tissue like structures. Bioink is extruded or transferred into a yield stress hydrogel or a microgel support bath allowing print needle motion during printing and providing temporal support for the printed construct. Although this technology has enabled creation of complex tissue structures, it remains a challenge to develop a support bath with user-defined extracellular mimetic cues and their spatial and temporal control. This is crucial to mimic the dynamic nature of the native tissue to better regenerate tissues and organs. To address this, we present a bioprinting approach involving printing of a photocurable viscous support layer and bioprinting of a cell-only or cell-laden bioink within this viscous layer followed by brief exposure to light to partially crosslink the support layer. This approach does not require shear thinning behavior and is suitable for a wide range of photocurable hydrogels to be used as a support. It enables multi-material printing to spatially control support hydrogel heterogeneity including temporal delivery of bioactive cues (e.g., growth factors), and precise patterning of dense multi-cellular structures within these hydrogel supports. Here, dense stem cell aggregates are printed within methacrylated hyaluronic acid-based hydrogels with patterned heterogeneity to spatially modulate human mesenchymal stem cell osteogenesis. This study has significant impactions on creating tissue interfaces (e.g., osteochondral tissue) in which spatial control of ECM properties for patterned stem cell differentiation is crucial.

Keywords:  bioinks; bone regeneration; embedded printing; human adult mesenchymal stem cells; stem cell differentiation; tissue engineering

DOI:  https://doi.org/10.1088/1758-5090/ad52f1
Biomed Mater. 2024 May 30.

Harnessing oriented arrangement of collagen fibers by 3D printing for enhancing mechanical and osteogenic properties of mineralized collagen scaffolds.

Yi Zhou, Xiaojie Lian, Yi Lu, Qi Zhu, Tong Fu, Haonan Feng, Qi Lei, Di Huang.

  As the structural basis of connective and load-bearing tissues, collagen fibers with orientation play an important role in the mechanical properties and physiological and biochemical functions of the tissues, but viable methods for preparing scaffolds with highly oriented collagenous structure still need to be further studied. In this study, pure collagen was used as printing ink to 3D printing. Harnessing oriented collagen fiber structure by 3D printing for promoting mechanical and osteogenic properties of scaffolds. The scaffolds with different printed angles and thicknesses were prepared to fit the bone defect site and realize personalized customization. The orientation assembly of collagen fibers was promoted by shear force action of 3D printing, the regular arrangement of collagen fibers and stabilization of fiber structure were promoted by pH adjustment and glutaraldehyde cross-linking, and the collagen fibers were mineralized by cyclic mineralization method. The microscopic morphology of fiber arrangement in the scaffolds were investigated by scanning electron microscopy. Results demonstrated that collagen fibers were changed from non-oriented to oriented after 3D printing. And the tensile modulus of the scaffolds with oriented collagen fibers was nine times higher than that of the scaffolds with non-oriented fibers. Moreover, the effects of oriented collagen fibers on the proliferation, differentiation and mineralization of MC3T3-E1 cells were studied by CCK-8 assay, live/dead cell staining, alkaline phosphatase activity test, and Alizarin red staining. The results indicated that cell proliferation, differentiation and mineralization were significantly promoted by oriented collagen fibers, and the cells proliferated directionally in the direction of the fibers. Taken together, mineralized collagen fiber scaffolds with oriented collagen fibers have great potential in bone tissue engineering applications.

Keywords:  3D printing; mineralized collagen fiber; oriented collagen fibers; tensile modulus

DOI:  https://doi.org/10.1088/1748-605X/ad5244
Crit Rev Ther Drug Carrier Syst. 2024 ;41(6): 89-110

Navigating the Challenges of 3D Printing Personalized Medicine in Space Explorations: A Comprehensive Review.

Prakash Katakam, Madhavi Lakshmi Ratna Bhavaraju, Tanniru Venkata Narayana, Koushik Bhandari, Nagarajan Sriram, Vidya Sagar Sisinty, Shanta Kumari Adiki.

Space exploration has undergone a paradigm shift in recent years, with a growing emphasis on long-duration missions and human habitation on other celestial bodies. Private aerospace businesses are at the forefront of advancing the next iteration of spacecraft, encompassing a wide range of applications such as deep space exploration (e.g., SpaceX) and cost-effective satellite deployments (e.g., Rocketlab). One of the critical challenges associated with prolonged space missions is the provision of personalized medical care. 3D printing technology has emerged as a potential solution, enabling the on-demand production of personalized medical devices and medications. However, the unique conditions of space pose substantial challenges to the successful implementation of 3D printing for personalized medicine. Tremendous scope for research exists in terms of resource utilization and waste management in space ecosystem, robotic and artificial intelligence (AI) enabled tool utilization, remote operability, interplanetary travel, space education and training tools, digital twins, space tourism and in many other aspects of 3D printing for personalized medicine in space explorations.

DOI: https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2024051126
Biofabrication. 2024 May 29.

3D bioprinting platform development for high-throughput cancer organoid models construction and drug evaluation.

Rui Dai, Wei Chen, You Chen, Jinlong Jin, Shiwei Zhang, Changhua Zhang, Jie Liu.

  The evaluation of anti-tumor drugs is critical for their development and clinical guidance. Tumor organoid models are gaining increased attention due to their ability to better mimic real tumor tissues, as well as lower time and economic costs, which makes up for the shortcomings of cell lines and xenograft models. However, current tumor organoid cultures based on the Matrigel have limitations in matching with high-throughput engineering methods due to slow gelation and low mechanical strength. Here, we present a novel composite bioink for culturing colorectal cancer organoids that provides an environment close to real tissue growth conditions and exhibits excellent photocrosslinking properties for rapid gel formation. Most importantly, the tumor organoids viability in the composite bioink after printing was as high as 97%, which also kept multicellular polar structures consistent with traditional culture methods in the Matrigel. Using 3D bioprinting with this composite bioink loaded with organoids, we demonstrated the feasibility of this drug evaluation model by validating it with clinically used colorectal cancer treatment drugs. Our results suggested that the composite bioink could effectively cultivate tumor organoids using 3D bioprinting, which had the potential to replace less reliable manual operations in promoting the application of tumor organoids in drug development and clinical guidance.

Keywords:  3D bioprinting; bioink; decellularized extracellular matrix (dECM); drug evaluation; organoid

DOI:  https://doi.org/10.1088/1758-5090/ad51a6
Future Sci OA. 2024 ;10(1): FSO973

3D-printed nanomedicines for cancer therapy.

Surbhi Bisht, Sweta Kanwal, Balasubramanian Mythili Gnanamangai, Swati Singh, Devayatbhai Baku Mansi, Ranvijay Kumar, Mayank Sharma, Piyush Kumar Gupta.



Keywords:  3D printing; cancer; nanomedicine; therapy

DOI:  https://doi.org/10.2144/fsoa-2024-0039
BMC Biotechnol. 2024 May 25. 24(1): 36

Activating the healing process: three-dimensional culture of stem cells in Matrigel for tissue repair.

Shukui Xu, Liru Zhao, Yinghui Li, Xiuge Gu, Ziyang Liu, Xing Han, Wenwen Li, Wensheng Ma.

   BACKGROUND: To establish a strategy for stem cell-related tissue regeneration therapy, human gingival mesenchymal stem cells (hGMSCs) were loaded with three-dimensional (3D) bioengineered Matrigel matrix scaffolds in high-cell density microtissues to promote local tissue restoration.
METHODS: The biological performance and stemness of hGMSCs under 3D culture conditions were investigated by viability and multidirectional differentiation analyses. A Sprague‒Dawley (SD) rat full-thickness buccal mucosa wound model was established, and hGMSCs/Matrigel were injected into the submucosa of the wound. Autologous stem cell proliferation and wound repair in local tissue were assessed by histomorphometry and immunohistochemical staining.
RESULTS: Three-dimensional suspension culture can provide a more natural environment for extensions and contacts between hGMSCs, and the viability and adipogenic differentiation capacity of hGMSCs were significantly enhanced. An animal study showed that hGMSCs/Matrigel significantly accelerated soft tissue repair by promoting autologous stem cell proliferation and enhancing the generation of collagen fibers in local tissue.
CONCLUSION: Three-dimensional cell culture with hydrogel scaffolds, such as Matrigel, can effectively improve the biological function and maintain the stemness of stem cells. The therapeutic efficacy of hGMSCs/Matrigel was confirmed, as these cells could effectively stimulate soft tissue repair to promote the healing process by activating the host microenvironment and autologous stem cells.

Keywords:  Gingival mesenchymal stem cells; Matrigel matrix; Soft tissue repair; Three-dimensional culture; Tissue engineering

DOI:  https://doi.org/10.1186/s12896-024-00862-5
Acta Biomater. 2024 May 28. pii: S1742-7061(24)00288-5. [Epub ahead of print]

Advancing Bone Regeneration: Unveiling the Potential of 3D Cell Models in the Evaluation of Bone Regenerative Materials.

Minglu Hao, Linyuan Xue, Xiaobo Wen, Li Sun, Lei Zhang, Kunyue Xing, Xiaokun Hu, Jiazhen Xu, Dongming Xing.

  Bone, a rigid yet regenerative tissue, has garnered extensive attention for its impressive healing abilities. Despite advancements in understanding bone repair and creating treatments for bone injuries, handling nonunions and large defects remains a major challenge in orthopedics. The rise of bone regenerative materials is transforming the approach to bone repair, offering innovative solutions for nonunions and significant defects, and thus reshaping orthopedic care. Evaluating these materials effectively is key to advancing bone tissue regeneration, especially in difficult healing scenarios, making it a critical research area. Traditional evaluation methods, including two-dimensional cell models and animal models, have limitations in predicting accurately. This has led to exploring alternative methods, like 3D cell models, which provide fresh perspectives for assessing bone materials' regenerative potential. This paper discusses various techniques for constructing 3D cell models, their pros and cons, and crucial factors to consider when using these models to evaluate bone regenerative materials. We also highlight the significance of 3D cell models in the in vitro assessments of these materials, discuss their current drawbacks and limitations, and suggest future research directions. STATEMENT OF SIGNIFICANCE: This work addresses the challenge of evaluating bone regenerative materials (BRMs) crucial for bone tissue engineering. It explores the emerging role of 3D cell models as superior alternatives to traditional methods for assessing these materials. By dissecting the construction, key factors of evaluating, advantages, limitations, and practical considerations of 3D cell models, the paper elucidates their significance in overcoming current evaluation method shortcomings. It highlights how these models offer a more physiologically relevant and ethically preferable platform for the precise assessment of BRMs. This contribution is particularly significant for "Acta Biomaterialia" readership, as it not only synthesizes current knowledge but also propels the discourse forward in the search for advanced solutions in bone tissue engineering and regeneration.

Keywords:  3D cell models; bone regenerative materials; in vitro models; material evaluation methods

DOI:  https://doi.org/10.1016/j.actbio.2024.05.041
J Contemp Brachytherapy. 2024 Apr;16(2): 156-169

Brachytherapy and 3D printing for skin cancer: A review paper.

Michal Poltorak, Pawel Banatkiewicz, Lukasz Poltorak, Piotr Sobolewski, Damian Zimon, Maciej Szwast, Irena Walecka.

  Brachytherapy is a type of radiation therapy, in which a radiation source is placed directly or close to a tumor. It is commonly used to treat skin cancer, and enables precise irradiation treatment of affected area (planning target volume - PTV) while minimizing exposure dose to surrounding healthy tissue (organs at risk - OARs). Recently, the use of 3D printing has begun revolutionizing brachytherapy, as it allows manufacturing of custom-designed applicators for unique shape of skin topography, tumor, and surrounding tissues. Outcome of the combination of 3D printing and brachytherapy has several advantages over traditional treatment planning methods. Some of the advantages are intuitive, whereas others can be concluded from a literature overview as follows: 1) Possibility of developing patient-specific applicators that precisely match the shape of tumor area; 2) Reduction of the time required for applicator production, especially when custom-made devices are needed; 3) Reduction of manufacturing costs; 4) Treatment procedures improvement; 5) Improvement of safety measures accelerated by the development of smart materials (e.g., polymer filaments with admixture of heavy elements); 6) Possibility of nearly instant adjustment into tumor treatment (applicators can be changed as the tumor is changing its shape); and 7) Applicators designed to securely fit to treatment area to hold radioactive source always in the same place for each fraction. Consequently, tumor-provided dose is accurate and leads to effective treatment. In this review paper, we investigated the current state-of-the-art of the application of 3D printing in brachytherapy. A number of existing reports were chosen and reviewed in terms of printing technology, materials used, treatment effectiveness, and fabrication protocols. Furthermore, the development of future directions that should be considered by collaborative teams bridging different fields of science, such as medicine, physics, chemistry, and material science were summarized. With the indicated topics, we hope to stimulate the innovative progress of 3D printing technology in brachytherapy.

Keywords:  3D printing; applicator design; individual applicator; skin cancer; superficial brachytherapy

DOI:  https://doi.org/10.5114/jcb.2024.137357
Small. 2024 May 28. e2403681

3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Xulin Hu, Jiao Chen, Shuhao Yang, Zhen Zhang, Haoming Wu, Jian He, Leilei Qin, Jianfei Cao, Chengdong Xiong, Kainan Li, Xian Liu, Zhiyong Qian.

  Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with β-tricalcium phosphate (β-TCP) and constructed a bionic cancellous bone scaffolding system α/β-tricalcium phosphate (α/β-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/β-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Keywords:  biomimetic scaffold; infections bone defect repair; tea polyphenol; tricalcium phosphate

DOI:  https://doi.org/10.1002/smll.202403681
Methods Mol Biol. 2024 May 25.

Development of a Three-Dimensional Multicellular Model of Human Neuroblastoma Using Matrigel as an Extracellular Matrix Analogue.

Kristina V Kitaeva, Valeriya V Solovyeva, Albert A Rizvanov.

  Neuroblastoma, the most prevalent extracranial solid tumor in children, poses therapeutic challenges due to its variable clinical course and propensity for metastasis. Despite advances in treatment strategies like chemotherapy, drug resistance remains a significant concern, highlighting the need for improved models to study tumor behavior and drug responses. This chapter proposes the development of a three-dimensional multicellular model of human neuroblastoma using Matrigel as an ECM analogue. Such models aim to replicate the complexity of the tumor microenvironment, providing valuable insights into tumor progression and drug resistance mechanisms. By recapitulating key features of neuroblastoma within a physiologically relevant context, these models offer a platform for preclinical drug screening and therapeutic development.

Keywords:  Co-culture; Matrigel; Mesenchymal stem cells; Neuroblastoma cells; Tumor cells

DOI:  https://doi.org/10.1007/7651_2024_548