bims-biprem 2023-07-09 papers

Issue of 2023–07–09
ten papers selected by
Seerat Maqsood, University of Teramo

Regen Med. 2023 Jul 05.

The regulatory challenge of 3D bioprinting.

Tajanka Mladenovska, Peter F Choong, Gordon G Wallace, Cathal D O'Connell.

New developments in additive manufacturing and regenerative medicine have the potential to radically disrupt the traditional pipelines of therapy development and medical device manufacture. These technologies present a challenge for regulators because traditional regulatory frameworks are designed for mass manufactured therapies, rather than bespoke solutions. 3D bioprinting technologies present another dimension of complexity through the inclusion of living cells in the fabrication process. Herein we overview the challenge of regulating 3D bioprinting in comparison to existing cell therapy products as well as custom-made 3D printed medical devices. We consider a range of specific challenges pertaining to 3D bioprinting in regenerative medicine, including classification, risk, standardization and quality control, as well as technical issues related to the manufacturing process and the incorporated materials and cells.

Keywords: biomaterials; bioprinting; bioreactors; legal/regulatory; regeneration; regulation; repair; stem cells; tissue engineering

DOI: https://doi.org/10.2217/rme-2022-0194

Front Bioeng Biotechnol. 2023 ;11 1221314

A tissue engineered 3D printed calcium alkali phosphate bioceramic bone graft enables vascularization and regeneration of critical-size discontinuity bony defects in vivo.

Christine Knabe, Michael Stiller, Marian Kampschulte, Janka Wilbig, Barbara Peleska, Jens Günster, Renate Gildenhaar, Georg Berger, Alexander Rack, Ulf Linow, Max Heiland, Carsten Rendenbach, Steffen Koerdt, Claudius Steffen, Alireza Houshmand, Li Xiang-Tischhauser, Doaa Adel-Khattab.

Introduction: Recently, efforts towards the development of patient-specific 3D printed scaffolds for bone tissue engineering from bioactive ceramics have continuously intensified. For reconstruction of segmental defects after subtotal mandibulectomy a suitable tissue engineered bioceramic bone graft needs to be endowed with homogenously distributed osteoblasts in order to mimic the advantageous features of vascularized autologous fibula grafts, which represent the standard of care, contain osteogenic cells and are transplanted with the respective blood vessel. Consequently, inducing vascularization early on is pivotal for bone tissue engineering. The current study explored an advanced bone tissue engineering approach combining an advanced 3D printing technique for bioactive resorbable ceramic scaffolds with a perfusion cell culture technique for pre-colonization with mesenchymal stem cells, and with an intrinsic angiogenesis technique for regenerating critical size, segmental discontinuity defects in vivo applying a rat model. To this end, the effect of differing Si-CAOP (silica containing calcium alkali orthophosphate) scaffold microarchitecture arising from 3D powder bed printing (RP) or the Schwarzwalder Somers (SSM) replica fabrication technique on vascularization and bone regeneration was analyzed in vivo. In 80 rats 6-mm segmental discontinuity defects were created in the left femur. Methods: Embryonic mesenchymal stem cells were cultured on RP and SSM scaffolds for 7d under perfusion to create Si-CAOP grafts with terminally differentiated osteoblasts and mineralizing bone matrix. These scaffolds were implanted into the segmental defects in combination with an arteriovenous bundle (AVB). Native scaffolds without cells or AVB served as controls. After 3 and 6 months, femurs were processed for angio-µCT or hard tissue histology, histomorphometric and immunohistochemical analysis of angiogenic and osteogenic marker expression. Results: At 3 and 6 months, defects reconstructed with RP scaffolds, cells and AVB displayed a statistically significant higher bone area fraction, blood vessel volume%, blood vessel surface/volume, blood vessel thickness, density and linear density than defects treated with the other scaffold configurations. Discussion: Taken together, this study demonstrated that the AVB technique is well suited for inducing adequate vascularization of the tissue engineered scaffold graft in segmental defects after 3 and 6 months, and that our tissue engineering approach employing 3D powder bed printed scaffolds facilitated segmental defect repair.

Keywords: 3D printed scaffold; angio-μCT; angiogenesis; bioactive ceramics; bone repair; bone tissue engineering; calcium alkali orthophosphates; segmental discontinuity bone defects

DOI: https://doi.org/10.3389/fbioe.2023.1221314

Mater Horiz. 2023 Jul 06.

3D multicellular micropatterning biomaterials for hair regeneration and vascularization.

Jingge Ma, Chen Qin, Jinfu Wu, Hui Zhuang, Lin Du, Jinfu Xu, Chengtie Wu.

Hair loss caused by the abnormal functions of hair follicles in skin can seriously impact the quality of an individual's life. The development of sophisticated skin tissue-engineered constructs is required to enable the function recovery of hair follicles. However, effective hair regrowth in skin substitutes still remains a great challenge. In this study, a 3D multicellular micropattern was successfully fabricated by arranging the hair follicle-related cells orderly distributed in the interval of vascular-cell networks via bioprinting technology. By combining the stable biomimetic micropattern structure and the bio-inducing substrate incorporated with magnesium silicate (MS) nanomaterials, the 3D multicellular micropattern possessed significant follicular potential and angiogenic capacity in vitro. Furthermore, the 3D multicellular micropattern with MS incorporation contributed to efficient hair regrowth during skin tissue regeneration in both immunodeficient mice and androgenetic alopecia (AGA) mice models. Thus, this study proposes a novel 3D micropatterned multicellular system assembling a biomimetic micro-structure and modulating the cell-cell interaction for hair regeneration during skin reconstruction.

DOI: https://doi.org/10.1039/d3mh00528c

Expert Rev Clin Pharmacol. 2023 Jul 05. 1-4

3D printing - an alternative strategy for pediatric medicines.

Alice P McCloskey, Louise Bracken, Nicola Vasey, Touraj Ehtezazi.

Keywords: 3D printing; children; medication adherence; medicines; pediatrics; solid oral dosage forms

DOI: https://doi.org/10.1080/17512433.2023.2233416

Thorac Surg Clin. 2023 Aug;pii: S1547-4127(23)00042-7. [Epub ahead of print]33(3): 273-281

Three-Dimensional Printing Applications in Thoracic Surgery.

Antonia A Pontiki, Kawal Rhode, Savvas Lampridis, Andrea Bille.

Advances in technology allowing the combination of medical imaging and three-dimensional printing have greatly benefitted thoracic surgery, allowing for the creation of complex prostheses. Surgical education is also a significant application of three-dimensional printing, especially for the development of simulation-based training models. Aiming to show how three-dimensional printing can benefit patients and clinicians in thoracic surgery, an optimized method to create patient-specific chest wall prosthesis using three-dimensional printing was developed and clinically validated. An artificial chest simulator for surgical training was also developed, replicating the human anatomy with high realism and accurately simulating a minimally invasive lobectomy.

Keywords: 3D printing; Chest-wall reconstruction; Lobectomy; Patient-specific prosthesis; Simulator; Surgical training

DOI: https://doi.org/10.1016/j.thorsurg.2023.04.012

Eng Life Sci. 2023 Jul;23(7): 2200140

Biocompatible scaffolds based on collagen and oxidized dextran for endothelial cell survival and function in tissue engineering.

Fatemeh Sabet Sarvestani, Ali-Mohammad Tamaddon, Ramin Yaghoobi, Bita Geramizadeh, Negar Azarpira.

Angiogenesis is a vital step in tissue regeneration. Hence, the current study aimed to prepare oxidized dextran (Odex)/collagen (Col)-hydrogels with laminin (LMN), as an angiogenic extracellular matrix (ECM) component, for promoting human umbilical vein endothelial cell (HUVEC) proliferation and function. Odex/Col scaffolds were constructed at various concentrations and temperatures. Using oscillatory rheometry, scanning electron microscopy (SEM), and cell viability testing, the scaffolds were characterized, and then HUVEC proliferation and function was compared with or without LMN. The gelation time could be modified by altering the Odex/Col mass ratio as well as the temperature. SEM showed that Odex/Col hydrogels had a more regular three-dimensional (3D) porous structure than the Col hydrogels. Moreover, HUVECs grew faster in the Col scaffold (12 mg/mL), whereas the Odex (30 mg/mL)/Col (6 mg/mL) scaffold exhibited the lowest apoptosis index. Furthermore, the expression level of vascular endothelial growth factor (VEGF) mRNA in the group without LMN was higher than that with LMN, and the Odex (30 mg/mL)/Col (6 mg/mL) scaffold without LMN had the highest VEGF protein secretion, allowing the cells to survive and function effectively. Odex/Col scaffolds, with or without LMN, are proposed as a tissue engineering construct to improve HUVEC survival and function for angiogenesis.

Keywords: collagen; endothelial cells; laminin; oxidized dextran; scaffold

DOI: https://doi.org/10.1002/elsc.202200140

Cell Death Discov. 2023 Jul 03. 9(1): 221

Human 3D brain organoids: steering the demolecularization of brain and neurological diseases.

Yogita K Adlakha.

Understanding of human brain development, dysfunction and neurological diseases has remained limited and challenging due to inability to recapitulate human brain-specific features in animal models. Though the anatomy and physiology of the human brain has been understood in a remarkable way using post-mortem, pathological samples of human and animal models, however, modeling of human brain development and neurological diseases remains a challenge owing to distinct complexity of human brain. In this perspective, three-dimensional (3D) brain organoids have shown a beam of light. Tremendous growth in stem cell technologies has permitted the differentiation of pluripotent stem cells under 3D culture conditions into brain organoids, which recapitulate the unique features of human brain in many ways and also offer the detailed investigation of brain development, dysfunction and neurological diseases. Their translational value has also emerged and will benefit the society once the protocols for the upscaling of brain organoids are in place. Here, we summarize new advancements in methods for generation of more complex brain organoids including vascularized and mixed lineage tissue from PSCs. How synthetic biomaterials and microfluidic technology is boosting brain organoid development, has also been highlighted. We discuss the applications of brain organoids in studying preterm birth associated brain dysfunction; viral infections mediated neuroinflammation, neurodevelopmental and neurodegenerative diseases. We also highlight the translational value of brain organoids and current challenges that the field is experiencing.

DOI: https://doi.org/10.1038/s41420-023-01523-w

Micromachines (Basel). 2023 Apr 19. pii: 878. [Epub ahead of print]14(4):

3D Bioprinting of an Endothelialized Liver Lobule-like Construct as a Tumor-Scale Drug Screening Platform.

Zicheng Fan, Xiaoyun Wei, Keke Chen, Ling Wang, Mingen Xu.

3D cell culture models replicating the complexity of cell-cell interactions and biomimetic extracellular matrix (ECM) are novel approaches for studying liver cancer, including in vitro drug screening or disease mechanism investigation. Although there have been advancements in the production of 3D liver cancer models to serve as drug screening platforms, recreating the structural architecture and tumor-scale microenvironment of native liver tumors remains a challenge. Here, using the dot extrusion printing (DEP) technology reported in our previous work, we fabricated an endothelialized liver lobule-like construct by printing hepatocyte-laden methacryloyl gelatin (GelMA) hydrogel microbeads and HUVEC-laden gelatin microbeads. DEP technology enables hydrogel microbeads to be produced with precise positioning and adjustable scale, facilitating the construction of liver lobule-like structures. The vascular network was achieved by sacrificing the gelatin microbeads at 37 °C to allow HUVEC proliferation on the surface of the hepatocyte layer. Finally, we used the endothelialized liver lobule-like constructs for anti-cancer drug (Sorafenib) screening, and stronger drug resistance results were obtained when compared to either mono-cultured constructs or hepatocyte spheroids alone. The 3D liver cancer models presented here successfully recreate liver lobule-like morphology, and may have the potential to serve as a liver tumor-scale drug screening platform.

Keywords: 3D bioprinting; GelMA hydrogel; drug screening; liver lobule-like construct

DOI: https://doi.org/10.3390/mi14040878

Cell Stem Cell. 2023 Jul 06. pii: S1934-5909(23)00215-1. [Epub ahead of print]30(7): 911-912

Prolonged 3D culture unlocks black box of primate embryogenesis.

Ziyi Li, Fan Zhou.

By developing in vitro 3D culture systems and identifying morphological and molecular events of early organogenesis, two recent studies1,2 reported exciting research advances in non-human primate embryo development.

DOI: https://doi.org/10.1016/j.stem.2023.06.004

Biomater Adv. 2023 Jun 21. pii: S2772-9508(23)00256-X. [Epub ahead of print]153 213533

Design of experiment and machine learning inform on the 3D printing of hydrogels for biomedical applications.

Neda Madadian Bozorg, Mickael Leclercq, Théophraste Lescot, Marc Bazin, Nicolas Gaudreault, Amrita Dikpati, Marc-André Fortin, Arnaud Droit, Nicolas Bertrand.

In the biomedical field, 3D printing has the potential to deliver on some of the promises of personalized therapy, notably by enabling point-of-care fabrication of medical devices, dosage forms and bioimplants. To achieve this full potential, a better understanding of the 3D printing processes is necessary, and non-destructive characterization methods must be developed. This study proposes methodologies to optimize the 3D printing parameters for soft material extrusion. We hypothesize that combining image processing with design of experiment (DoE) analyses and machine learning could help obtaining useful information from a quality-by-design perspective. Herein, we investigated the impact of three critical process parameters (printing speed, printing pressure and infill percentage) on three critical quality attributes (gel weight, total surface area and heterogeneity) monitored with a non-destructive methodology. DoE and machine learning were combined to obtain information on the process. This work paves the way for a rational approach to optimize 3D printing parameters in the biomedical field.

Keywords: 3D printing technology; Image processing; Machine learning; Personalized medication; Pharmaceutical sciences; Statistical analysis

DOI: https://doi.org/10.1016/j.bioadv.2023.213533