bims-biprem 2024-01-14 papers

bims-biprem

Biomed News

on Bioprinting for regenerative medicine

Issue of 2024–01–14
nine papers selected by
Seerat Maqsood, University of Teramo

3D Bioprinting of Organoids: past, present, and prospective.
Design of bone scaffolds with calcium phosphate and its derivatives by 3D printing: A review.
DeepFreeze 3D-biofabrication for Bioengineering and Storage of Stem Cells in Thick and Large-Scale Human Tissue Analogs.
3D bioprinting bioglass to construct vascularized full-thickness skin substitutes for wound healing.
Upconversion 3d Bioprinting for Noninvasive In-Vivo Moulding.
Approaching 3D printing in oral and maxillofacial surgery - suggestions for structured clinical standards.
Assessing the advantages of 3D bioprinting and 3D spheroids in deciphering the osteoarthritis healing mechanism using human chondrocytes and polarized macrophages.
3D printed bioabsorbable composite scaffolds of poly (lactic acid)-tricalcium phosphate-ceria with osteogenic property for bone regeneration.
Bioprinting: Mechanical Stabilization and Reinforcement Strategies in Regenerative Medicine.

Tissue Eng Part A. 2024 Jan 11.

3D Bioprinting of Organoids: past, present, and prospective.

Mariana Cabral, Ke Cheng, Donghui Zhu.

Organoids are 3D in vitro tissue models that are derived from stem cells and can closely mimic the structure and function of human organs. The ability to create organoids that recapitulate the complex cellular architecture of organs has emerged as an innovative technique in biomedical research and drug development. However, traditional methods of organoid culture are time-consuming and often yield low quantities of cells, which has led to the development of 3D bioprinting of organoids from bioinks containing suspended cells and desired scaffolds. A comparison across different organoid-building techniques, focusing on 3D bioprinting and its benefits may be helpful and was yet to be distinguished. The goal of this review is to provide an overview of the current state of 3D bioprinting of organoids and its potential applications in tissue engineering, drug screening, and regenerative medicine.

DOI: https://doi.org/10.1089/ten.TEA.2023.0209
J Mech Behav Biomed Mater. 2024 Jan 09. pii: S1751-6161(24)00023-7. [Epub ahead of print]151 106391

Design of bone scaffolds with calcium phosphate and its derivatives by 3D printing: A review.

Seyedeh Farnaz Darghiasi, Ashkan Farazin, Hanieh Sadat Ghazali.

  Tissue engineering is a fascinating field that combines biology, engineering, and medicine to create artificial tissues and organs. It involves using living cells, biomaterials, and bioengineering techniques to develop functional tissues that can be used to replace or repair damaged or diseased organs in the human body. The process typically starts by obtaining cells from the patient or a donor. These cells are then cultured and grown in a laboratory under controlled conditions. Scaffold materials, such as biodegradable polymers or natural extracellular matrices, are used to provide support and structure for the growing cells. 3D bone scaffolds are a fascinating application within the field of tissue engineering. These scaffolds are designed to mimic the structure and properties of natural bone tissue and serve as a temporary framework for new bone growth. The main purpose of a 3D bone scaffold is to provide mechanical support to the surrounding cells and guide their growth in a specific direction. It acts as a template, encouraging the formation of new bone tissue by providing a framework for cells to attach, proliferate, and differentiate. These scaffolds are typically fabricated using biocompatible materials like ceramics, polymers, or a combination of both. The choice of material depends on factors such as strength, biodegradability, and the ability to facilitate cell adhesion and growth. Advanced techniques like 3D printing have revolutionized the fabrication process of these scaffolds. Using precise layer-by-layer deposition, it allows for the creation of complex, patient-specific geometries, mimicking the intricacies of natural bone structure. This article offers a brief overview of the latest developments in the research and development of 3D printing techniques for creating scaffolds used in bone tissue engineering.

Keywords:  3D printing; Biodegradability; Biomaterials; Bone scaffold; Cell adhesion; Tissue engineering

DOI:  https://doi.org/10.1016/j.jmbbm.2024.106391
Adv Sci (Weinh). 2024 Jan 06. e2306683

DeepFreeze 3D-biofabrication for Bioengineering and Storage of Stem Cells in Thick and Large-Scale Human Tissue Analogs.

Alok Kumar, Robert A Brown, Daniel Benyamien Roufaeil, Aditi Gupta, Erika L Lipford, Divya Muthusamy, Amihai Zalzman, Ronna Hertzano, Tao Lowe, Joseph P Stains, Michal Zalzman.

  3D bioprinting holds great promise for meeting the increasing need for transplantable tissues and organs. However, slow printing, interlayer mixing, and the extended exposure of cells to non-physiological conditions in thick structures still hinder clinical applications. Here the DeepFreeze-3D (DF-3D) procedure and bioink for creating multilayered human-scale tissue mimetics is presented for the first time. The bioink is tailored to support stem cell viability, throughout the rapid freeform DF-3D biofabrication process. While the printer nozzle is warmed to room temperature, each layer solidifies at contact with the stage (-80 °C), or the subsequent layers, ensuring precise separation. After thawing, the encapsulated stem cells remain viable without interlayer mixing or delamination. The composed cell-laden constructs can be cryogenically stored and thawed when needed. Moreover, it is shown that under inductive conditions the stem cells differentiate into bone-like cells and grow for months after thawing, to form large tissue-mimetics in the scale of centimeters. This is important, as this approach allows the generation and storage of tissue mimetics in the size and thickness of human tissues. Therefore, DF-3D biofabrication opens new avenues for generating off-the-shelf human tissue analogs. It further holds the potential for regenerative treatments and for studying tissue pathologies caused by disease, tumor, or trauma.

Keywords:  3D printing; 3D scaffolds; biofabrication; bioinks; regeneration; regenerative medicines; stem cells; tissue engineering

DOI:  https://doi.org/10.1002/advs.202306683
Mater Today Bio. 2024 Feb;24 100899

3D bioprinting bioglass to construct vascularized full-thickness skin substitutes for wound healing.

Yanyan Liu, Xin Liu, Haitao Guo, Xinhuan Wang, Ailing Li, Dong Qiu, Qi Gu.

  Constructing three-dimensional (3D) bioprinted skin tissues that accurately replicate the mechanical properties of native skin and provide adequate oxygen and nutrient support remains a formidable challenge. In this study, we incorporated phosphosilicate calcium bioglasses (PSCs), a type of bioactive glass (BG), into the bioinks used for 3D bioprinting. The resulting bioink exhibited mechanical properties and biocompatibility that closely resembled those of natural skin. Utilizing 3D bioprinting technology, we successfully fabricated full-thickness skin substitutes, which underwent comprehensive evaluation to assess their regenerative potential in treating full-thickness skin injuries in rats. Remarkably, the skin substitutes loaded with PSCs exhibited exceptional angiogenic activity, as evidenced by the upregulation of angiogenesis-related genes in vitro and the observation of enhanced vascularization in wound tissue sections in vivo. These findings conclusively demonstrated the outstanding efficacy of PSCs in promoting angiogenesis and facilitating the repair of full-thickness skin wounds. The insights garnered from this study provide a valuable reference strategy for the development of skin tissue grafts with potent angiogenesis-inducing capabilities.

Keywords:  3D printing; Angiogenesis; Artificial skin substitutes; Bioactive glass; Wound healing

DOI:  https://doi.org/10.1016/j.mtbio.2023.100899
Adv Mater. 2024 Jan 11. e2310617

Upconversion 3d Bioprinting for Noninvasive In-Vivo Moulding.

Peng Zhang, Zhaowei Teng, Min Zhou, Xue Yu, Hongyu Wen, Junzheng Niu, Zhichao Liu, Zhimeng Zhang, Yang Liu, Jianbei Qiu, Xuhui Xu.

  Tissue engineered bracket materials provide essential support for the physiological protection and therapeutics of patients. Unfortunately, the implantation process of such devices poses the risk of surgical complications and infection. In this study, an upconversion nanoparticles (UCNPs)-assisted 3D bioprinting approach was developed to realise in-vivo moulding that is free from invasive surgery. Reasonably designed UCNPs, which convert near-infrared (NIR) photons that penetrate skin tissues into blue-violet emission (300-500 nm), induce a monomer polymerisation curing procedure in-vivo. Using a fused deposition modeling coordination framework, a precisely predetermined trajectory of the NIR laser enabled the manufacture of implantable medical devices with tailored shapes. A proof of the 3D bioprinting of a noninvasive fracture fixation scaffold was achieved successfully, thus demonstrating an entirely new method of in-vivo moulding for biomedical treatment. This article is protected by copyright. All rights reserved.

Keywords:  3D bioprinting; Multi-photon polymerization hydrogels; Noninvasive moulding; UCNPs

DOI:  https://doi.org/10.1002/adma.202310617
Oral Maxillofac Surg. 2024 Jan 12.

Approaching 3D printing in oral and maxillofacial surgery - suggestions for structured clinical standards.

Elisabeth Goetze, Alexander-N Zeller, Andreas Pabst.

   PURPOSE: With respect to the European Union 2017 amendment of the Medical Device Regulations (MDR), this overview article presents recommendations concerning medical 3D printing in oral and maxillofacial surgery (OMFS).
METHODS: The MDR were screened for applicability of the rules to medical in-house 3D printing. Applicable regulations were summarized and compared to the status of medical use of 3D printing in OMFS in Germany. Recommendations were made for MDR concerning medical 3D printing.
RESULTS: In-house printed models, surgical guides, and implants fall under the category of Class I-III, depending on their invasive and active properties. In-house medical 3D printing for custom-made medical devices is possible under certain prerogatives: (1) the product is not being used in another facility, (2) appropriate quality systems are applied, (3) the reason for omitting commercial products is documented, (4) information about its use is supplied to the responsible authority, (5) there is a publicly accessible declaration of origin, identification, and conformity to the MDR, (6) there are records of manufacturing site, process and performance data, (7) all products are produced according to the requirements proclaimed before, and (8) there is an evaluation of clinical use and correction of possible issues.
CONCLUSION: Several aspects must be addressed for in house medical 3D printing, according to the MDR. Devising MDR related to medical 3D printing is a growing challenge. The implementation of recommendations in OMFS could help practitioners to overcome the challenges and become aware of the in-house production and application of 3D printed devices.

Keywords:  3D printing; European Union; Guideline; Medical Device Regulation; Recommendation; SOP

DOI:  https://doi.org/10.1007/s10006-024-01208-3
Biomed Mater. 2024 Jan 10.

Assessing the advantages of 3D bioprinting and 3D spheroids in deciphering the osteoarthritis healing mechanism using human chondrocytes and polarized macrophages.

Nilotpal Majumder, Subhadeep Roy, Aarushi Sharma, Shuchi Arora, Raju Vaishya, Amitabha Bandyopadhyay, Sourabh Ghosh.

  The molecular niche of an osteoarthritic microenvironment comprises of the native chondrocytes, the circulatory immune cells, and their respective inflammatory mediators. Although, M2 macrophages infiltrate the joint tissue during osteoarthritis (OA) to initiate cartilage repair, the mechanistic crosstalk that dwells underneath is still unknown. Our study established a co-culture system of human OA chondrocytes and M2 macrophages in 3D spheroids and 3D bioprinted silk-gelatin constructs. It is already well established that Silk fibroin-gelatin bioink support chondrogenic differentiation due to upregulation in Wnt/β-catenin pathway. Additionally, the presence of anti-inflammatory M2 macrophages significantly upregulated the expression of chondrogenic biomarkers (COL-II, ACAN) with an attenuated expression of the chondrocyte hypertrophy (COL-X), chondrocyte dedifferentiation (COL-I) and matrix catabolism (MMP-1 and MMP-13) genes even in the absence of the interleukins. Furthermore, the 3D bioprinted co-culture model displayed an upper hand in stimulating cartilage regeneration and OA inhibition than the spheroid model, underlining the role of silk fibroin-gelatin in encouraging chondrogenesis. Additionally, the 3D bioprinted silk-gelatin constructs further supported the maintenance of stable anti-inflammatory phenotype of M2 macrophage. Thus, the direct interaction between the primary OAC and M2 macrophages in 3D context along with the release of the soluble anti-inflammatory factors by the M2 cells significantly contributed to a better understanding regarding the molecular mechanisms responsible for immune cell-mediated OA healing.&#xD.

Keywords:  3D bioprinting; 3D spheroid; M2 macrophage; Osteoarthritis; Primary Chondrocytes

DOI:  https://doi.org/10.1088/1748-605X/ad1d18
Biomater Biosyst. 2024 Mar;13 100086

3D printed bioabsorbable composite scaffolds of poly (lactic acid)-tricalcium phosphate-ceria with osteogenic property for bone regeneration.

Samarah V Harb, Elayaraja Kolanthai, Abinaya S Pugazhendhi, Cesar A G Beatrice, Leonardo A Pinto, Craig J Neal, Eduardo H Backes, Ana C C Nunes, Heloisa S Selistre-de-Araújo, Lidiane C Costa, Melanie J Coathup, Sudipta Seal, Luiz A Pessan.

  The fabrication of customized implants by additive manufacturing has allowed continued development of the personalized medicine field. Herein, a 3D-printed bioabsorbable poly (lactic acid) (PLA)- β-tricalcium phosphate (TCP) (10 wt %) composite has been modified with CeO2 nanoparticles (CeNPs) (1, 5 and 10 wt %) for bone repair. The filaments were prepared by melt extrusion and used to print porous scaffolds. The nanocomposite scaffolds possessed precise structure with fine print resolution, a homogenous distribution of TCP and CeNP components, and mechanical properties appropriate for bone tissue engineering applications. Cell proliferation assays using osteoblast cultures confirmed the cytocompatibility of the composites. In addition, the presence of CeNPs enhanced the proliferation and differentiation of mesenchymal stem cells; thereby, increasing alkaline phosphatase (ALP) activity, calcium deposition and bone-related gene expression. Results from this study have shown that the 3D printed PLA-TCP-10%CeO2 composite scaffold could be used as an alternative polymeric implant for bone tissue engineering applications: avoiding additional/revision surgeries and accelerating the regenerative process.

Keywords:  Additive manufacturing; Biomaterial; Bone tissue engineering; Ceria nanoparticle; Polymer-matrix composites

DOI:  https://doi.org/10.1016/j.bbiosy.2023.100086
Tissue Eng Part A. 2024 Jan 11.

Bioprinting: Mechanical Stabilization and Reinforcement Strategies in Regenerative Medicine.

Ashleigh Ballard, Rebecca Patush, Jenesis Perez, Carmen Juarez, Alina Kirillova.

Bioprinting describes the printing of biomaterials and cell-laden or cell-free hydrogels with various combinations of embedded bioactive molecules. It encompasses the precise patterning of biomaterials and cells to create scaffolds for different biomedical needs. There are many requirements that bioprinting scaffolds face, and it is ultimately the interplay between the scaffold's structure, properties, processing, and performance that will lead to its successful translation. Among the essential properties that the scaffolds must possess - adequate and appropriate application-specific chemical, mechanical, and biological performance, the mechanical behavior of hydrogel-based bioprinted scaffolds is the key to their stable performance in vivo at the site of implantation. Hydrogels that typically constitute the main scaffold material and the medium for the cells and biomolecules are very soft and often lack sufficient mechanical stability, which reduces their printability and, therefore, the bioprinting potential. The aim of this review paper is to highlight the reinforcement strategies that are used in different bioprinting approaches to achieve enhanced mechanical stability of the bioinks and the printed scaffolds. Enabling stable and robust materials for the bioprinting processes will lead to the creation of truly complex and remarkable printed structures that could accelerate the application of smart, functional scaffolds in biomedical settings.

DOI: https://doi.org/10.1089/ten.TEA.2023.0239