bims-biprem 2023-05-28 papers

bims-biprem

Biomed News

on Bioprinting for regenerative medicine

Issue of 2023–05–28
fourteen papers selected by
Seerat Maqsood, University of Teramo

Additive Manufacturing and Physicomechanical Characteristics of PEGDA Hydrogels: Recent Advances and Perspective for Tissue Engineering.
Strategies for improving the 3D printability of decellularized extracellular matrix bioink.
Human mesenchymal stem cells and innovative scaffolds for bone tissue engineering applications.
Implant Imaging: Perspectives of Nuclear Imaging in Implant, Biomaterial, and Stem Cell Research.
3D Bioprinting for Vascularization.
New Challenges and Prospective Applications of Three-Dimensional Bioactive Polymeric Hydrogels in Oral and Craniofacial Tissue Engineering: A Narrative Review.
Biomechanical and Biological Characterization of XGel, a Human-Derived Hydrogel for Stem Cell Expansion and Tissue Engineering.
Recent Methods for Modifying Mechanical Properties of Tissue-Engineered Scaffolds for Clinical Applications.
Hydrogel Drug Delivery Systems for Bone Regeneration.
Organoids: The current status and biomedical applications.
3D bioprinting patient-derived induced pluripotent stem cell models of Alzheimer's disease using a smart bioink.
Internally crosslinked alginate-based bioinks for the fabrication of in vitro hepatic tissue models.
In Vitro Bone Differentiation of 3D Microsphere from Dental Pulp-Mesenchymal Stem Cells.
Human Ovarian Follicular Fluid Mesenchymal Stem Cells Express Osteogenic Markers When Cultured on Bioglass 58S-Coated Titanium Scaffolds.

Polymers (Basel). 2023 May 17. pii: 2341. [Epub ahead of print]15(10):

Additive Manufacturing and Physicomechanical Characteristics of PEGDA Hydrogels: Recent Advances and Perspective for Tissue Engineering.

Mohammad Hakim Khalili, Rujing Zhang, Sandra Wilson, Saurav Goel, Susan A Impey, Adrianus Indrat Aria.

  In this brief review, we discuss the recent advancements in using poly(ethylene glycol) diacrylate (PEGDA) hydrogels for tissue engineering applications. PEGDA hydrogels are highly attractive in biomedical and biotechnology fields due to their soft and hydrated properties that can replicate living tissues. These hydrogels can be manipulated using light, heat, and cross-linkers to achieve desirable functionalities. Unlike previous reviews that focused solely on material design and fabrication of bioactive hydrogels and their cell viability and interactions with the extracellular matrix (ECM), we compare the traditional bulk photo-crosslinking method with the latest three-dimensional (3D) printing of PEGDA hydrogels. We present detailed evidence combining the physical, chemical, bulk, and localized mechanical characteristics, including their composition, fabrication methods, experimental conditions, and reported mechanical properties of bulk and 3D printed PEGDA hydrogels. Furthermore, we highlight the current state of biomedical applications of 3D PEGDA hydrogels in tissue engineering and organ-on-chip devices over the last 20 years. Finally, we delve into the current obstacles and future possibilities in the field of engineering 3D layer-by-layer (LbL) PEGDA hydrogels for tissue engineering and organ-on-chip devices.

Keywords:  hydrogels; poly(ethylene glycol)diacrylate; printing; three-dimensional; tissue engineering

DOI:  https://doi.org/10.3390/polym15102341
Theranostics. 2023 ;13(8): 2562-2587

Strategies for improving the 3D printability of decellularized extracellular matrix bioink.

Huihui Zhang, Yilin Wang, Zijun Zheng, Xuerong Wei, Lianglong Chen, Yaobin Wu, Wenhua Huang, Lei Yang.

  3D bioprinting is a revolutionary technology capable of replicating native tissue and organ microenvironments by precisely placing cells into 3D structures using bioinks. However, acquiring the ideal bioink to manufacture biomimetic constructs is challenging. A natural extracellular matrix (ECM) is an organ-specific material that provides physical, chemical, biological, and mechanical cues that are hard to mimic using a small number of components. Organ-derived decellularized ECM (dECM) bioink is revolutionary and has optimal biomimetic properties. However, dECM is always "non-printable" owing to its poor mechanical properties. Recent studies have focused on strategies to improve the 3D printability of dECM bioink. In this review, we highlight the decellularization methods and procedures used to produce these bioinks, effective methods to improve their printability, and recent advances in tissue regeneration using dECM-based bioinks. Finally, we discuss the challenges associated with manufacturing dECM bioinks and their potential large-scale applications.

Keywords:  3D bioprinting; bioink; decellularized extracellular matrix; microenvironment; tissue regeneration

DOI:  https://doi.org/10.7150/thno.81785
Tissue Eng Part B Rev. 2023 May 22.

Human mesenchymal stem cells and innovative scaffolds for bone tissue engineering applications.

Elisa Mazzoni, Maria Rosa Iaquinta, Maria Mosaico, Raffaella De Pace, Antonio D'Agostino, Mauro Tognon, Fernanda Martini.

Stem cell-based therapy is a significant topic in regenerative medicine, with a predominant role being played by human mesenchymal stem cells (hMSCs). The hMSCs have been shown to be suitable in regenerative medicine for the treatment of bone tissue. In the last few years, the average lifespan of our population has gradually increased. The need of biocompatible materials, which exhibit high performances, such as efficiency in bone regeneration, has been highlighted by aging. Current studies emphasize the benefit of using biomimetic biomaterials, also known as scaffolds, for bone grafts to speed up bone repair at the fracture site. For the healing of injured bone and bone regeneration, regenerative medicine techniques utilizing a combination of these biomaterials, together with cells and bioactive substances, have drawn a great interest. Cell therapy, based on the use of hMSCs, alongside materials for the healing of damaged bone, has been obtained promising results. In this work, several aspects of cell biology, tissue engineering and biomaterials applied to bone healing/regrowth will be considered. In addition, the role of hMSCs in these fields and recent progress in clinical applications are discussed.

DOI: https://doi.org/10.1089/ten.TEB.2022.0217
Bioengineering (Basel). 2023 Apr 25. pii: 521. [Epub ahead of print]10(5):

Implant Imaging: Perspectives of Nuclear Imaging in Implant, Biomaterial, and Stem Cell Research.

Andras Polyak, Zita Képes, György Trencsényi.

  Until now, very few efforts have been made to specifically trace, monitor, and visualize implantations, artificial organs, and bioengineered scaffolds for tissue engineering in vivo. While mainly X-Ray, CT, and MRI methods have been used for this purpose, the applications of more sensitive, quantitative, specific, radiotracer-based nuclear imaging techniques remain a challenge. As the need for biomaterials increases, so does the need for research tools to evaluate host responses. PET (positron emission tomography) and SPECT (single photon emission computer tomography) techniques are promising tools for the clinical translation of such regenerative medicine and tissue engineering efforts. These tracer-based methods offer unique and inevitable support, providing specific, quantitative, visual, non-invasive feedback on implanted biomaterials, devices, or transplanted cells. PET and SPECT can improve and accelerate these studies through biocompatibility, inertivity, and immune-response evaluations over long investigational periods at high sensitivities with low limits of detection. The wide range of radiopharmaceuticals, the newly developed specific bacteria, and the inflammation of specific or fibrosis-specific tracers as well as labeled individual nanomaterials can represent new, valuable tools for implant research. This review aims to summarize the opportunities of nuclear-imaging-supported implant research, including bone, fibrosis, bacteria, nanoparticle, and cell imaging, as well as the latest cutting-edge pretargeting methods.

Keywords:  CT; PET; SPECT; bioengineering; biomaterial; implant; liposomes; nanoparticles; stem cell; tissue engineering

DOI:  https://doi.org/10.3390/bioengineering10050521
Bioengineering (Basel). 2023 May 18. pii: 606. [Epub ahead of print]10(5):

3D Bioprinting for Vascularization.

Amatullah Mir, Eugenia Lee, Wesley Shih, Sarah Koljaka, Anya Wang, Caitlin Jorgensen, Riley Hurr, Amartya Dave, Krupa Sudheendra, Narutoshi Hibino.

  In the world of clinic treatments, 3D-printed tissue constructs have emerged as a less invasive treatment method for various ailments. Printing processes, scaffold and scaffold free materials, cells used, and imaging for analysis are all factors that must be observed in order to develop successful 3D tissue constructs for clinical applications. However, current research in 3D bioprinting model development lacks diverse methods of successful vascularization as a result of issues with scaling, size, and variations in printing method. This study analyzes the methods of printing, bioinks used, and analysis techniques in 3D bioprinting for vascularization. These methods are discussed and evaluated to determine the most optimal strategies of 3D bioprinting for successful vascularization. Integrating stem and endothelial cells in prints, selecting the type of bioink according to its physical properties, and choosing a printing method according to physical properties of the desired printed tissue are steps that will aid in the successful development of a bioprinted tissue and its vascularization.

Keywords:  3D modeling; 3D printing; 3D tissues; 3D-printed sensors; bioinks; biomanufacturing; biomechanics; bioprinting; bone; hard tissue; oral diseases; organ-on-a-chip; scaffolds; skin; soft tissue; spheroids; stem cells; tissue engineering; vascularization; vasculature

DOI:  https://doi.org/10.3390/bioengineering10050606
Pharmaceuticals (Basel). 2023 May 05. pii: 702. [Epub ahead of print]16(5):

New Challenges and Prospective Applications of Three-Dimensional Bioactive Polymeric Hydrogels in Oral and Craniofacial Tissue Engineering: A Narrative Review.

Gamal Abdel Nasser Atia, Hany K Shalaby, Naema Goda Ali, Shaimaa Mohammed Morsy, Mohamed Mohamady Ghobashy, Hager Abdel Nasser Attia, Paritosh Barai, Norhan Nady, Ahmad S Kodous, Hasi Rani Barai.

  Regenerative medicine, and dentistry offers enormous potential for enhancing treatment results and has been fueled by bioengineering breakthroughs over the previous few decades. Bioengineered tissues and constructing functional structures capable of healing, maintaining, and regenerating damaged tissues and organs have had a broad influence on medicine and dentistry. Approaches for combining bioinspired materials, cells, and therapeutic chemicals are critical in stimulating tissue regeneration or as medicinal systems. Because of its capacity to maintain an unique 3D form, offer physical stability for the cells in produced tissues, and replicate the native tissues, hydrogels have been utilized as one of the most frequent tissue engineering scaffolds during the last twenty years. Hydrogels' high water content can provide an excellent conditions for cell viability as well as an architecture that mimics real tissues, bone, and cartilage. Hydrogels have been used to enable cell immobilization and growth factor application. This paper summarizes the features, structure, synthesis and production methods, uses, new challenges, and future prospects of bioactive polymeric hydrogels in dental and osseous tissue engineering of clinical, exploring, systematical and scientific applications.

Keywords:  hydrogel scaffolds; polymeric hydrogels and tissues regeneration; three dimensional; tissue engineering

DOI:  https://doi.org/10.3390/ph16050702
Adv Biol (Weinh). 2023 May 26. e2200332

Biomechanical and Biological Characterization of XGel, a Human-Derived Hydrogel for Stem Cell Expansion and Tissue Engineering.

Jorge A Belgodere, Haley R Lassiter, Jordan T Robinson, Katie M Hamel, Emma L Rogers, Omair A Mohiuddin, Liwen Zhang, Xiying Wu, Jeffrey M Gimble, Trivia P Frazier, William T Monroe, Cecilia G Sanchez.

  Hydrogels are 3D scaffolds used as alternatives to in vivo models for disease modeling and delivery of cells and drugs. Existing hydrogel classifications include synthetic, recombinant, chemically defined, plant- or animal-based, and tissue-derived matrices. There is a need for materials that can support both human tissue modeling and clinically relevant applications requiring stiffness tunability. Human-derived hydrogels are not only clinically relevant, but they also minimize the use of animal models for pre-clinical studies. This study aims to characterize XGel, a new human-derived hydrogel as an alternative to current murine-derived and synthetic recombinant hydrogels that features unique physiochemical, biochemical, and biological properties that support adipocyte and bone differentiation. Rheology studies determine the viscosity, stiffness, and gelation features of XGel. Quantitative studies for quality control support consistency in the protein content between lots. Proteomics studies reveal that XGel is predominantly composed of extracellular matrix proteins, including fibrillin, collagens I-VI, and fibronectin. Electron microscopy of the hydrogel provides phenotypic characteristics in terms of porosity and fiber size. The hydrogel demonstrates biocompatibility as a coating material and as a 3D scaffold for the growth of multiple cell types. The results provide insight into the biological compatibility of this human-derived hydrogel for tissue engineering.

Keywords:  Matrigel; human derived; hydrogels; microphysiological systems; rheology

DOI:  https://doi.org/10.1002/adbi.202200332
Biomimetics (Basel). 2023 May 16. pii: 205. [Epub ahead of print]8(2):

Recent Methods for Modifying Mechanical Properties of Tissue-Engineered Scaffolds for Clinical Applications.

Andrew Johnston, Anthony Callanan.

  The limited regenerative capacity of the human body, in conjunction with a shortage of healthy autologous tissue, has created an urgent need for alternative grafting materials. A potential solution is a tissue-engineered graft, a construct which supports and integrates with host tissue. One of the key challenges in fabricating a tissue-engineered graft is achieving mechanical compatibility with the graft site; a disparity in these properties can shape the behaviour of the surrounding native tissue, contributing to the likelihood of graft failure. The purpose of this review is to examine the means by which researchers have altered the mechanical properties of tissue-engineered constructs via hybrid material usage, multi-layer scaffold designs, and surface modifications. A subset of these studies which has investigated the function of their constructs in vivo is also presented, followed by an examination of various tissue-engineered designs which have been clinically translated.

Keywords:  3D printing; biomimetic; electrospinning; scaffold; tissue engineering

DOI:  https://doi.org/10.3390/biomimetics8020205
Pharmaceutics. 2023 Apr 25. pii: 1334. [Epub ahead of print]15(5):

Hydrogel Drug Delivery Systems for Bone Regeneration.

Long Bai, Gang Tao, Maogeng Feng, Yuping Xie, Shuyu Cai, Shuanglin Peng, Jingang Xiao.

  With the in-depth understanding of bone regeneration mechanisms and the development of bone tissue engineering, a variety of scaffold carrier materials with desirable physicochemical properties and biological functions have recently emerged in the field of bone regeneration. Hydrogels are being increasingly used in the field of bone regeneration and tissue engineering because of their biocompatibility, unique swelling properties, and relative ease of fabrication. Hydrogel drug delivery systems comprise cells, cytokines, an extracellular matrix, and small molecule nucleotides, which have different properties depending on their chemical or physical cross-linking. Additionally, hydrogels can be designed for different types of drug delivery for specific applications. In this paper, we summarize recent research in the field of bone regeneration using hydrogels as delivery carriers, detail the application of hydrogels in bone defect diseases and their mechanisms, and discuss future research directions of hydrogel drug delivery systems in bone tissue engineering.

Keywords:  bone immunomodulation; bone regeneration; cartilage regeneration; drug delivery systems; hydrogels; mesenchymal stem cells; tissue engineering

DOI:  https://doi.org/10.3390/pharmaceutics15051334
MedComm (2020). 2023 Jun;4(3): e274

Organoids: The current status and biomedical applications.

Siqi Yang, Haijie Hu, Hengchung Kung, Ruiqi Zou, Yushi Dai, Yafei Hu, Tiantian Wang, Tianrun Lv, Jun Yu, Fuyu Li.

  Organoids are three-dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self-organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long-term maintenance of the function and biological characteristics of the parental cells in vitro. All these features of organoids open up new opportunities for drug discovery, large-scale drug screening, and precision medicine. Another major application of organoids is disease modeling, and especially various hereditary diseases that are difficult to model in vitro have been modeled with organoids by combining genome editing technologies. Herein, we introduce the development and current advances in the organoid technology field. We focus on the applications of organoids in basic biology and clinical research, and also highlight their limitations and future perspectives. We hope that this review can provide a valuable reference for the developments and applications of organoids.

Keywords:  3D culture; drug screening; precision medicine; stem cells; tumoroid

DOI:  https://doi.org/10.1002/mco2.274
Bioelectron Med. 2023 May 24. 9(1): 10

3D bioprinting patient-derived induced pluripotent stem cell models of Alzheimer's disease using a smart bioink.

Claire Benwood, Jonathan Walters-Shumka, Kali Scheck, Stephanie M Willerth.

   BACKGROUND: Alzheimer's disease (AD), a progressive neurodegenerative disorder, is becoming increasingly prevalent as our population ages. It is characterized by the buildup of amyloid beta plaques and neurofibrillary tangles containing hyperphosphorylated-tau. The current treatments for AD do not prevent the long-term progression of the disease and pre-clinical models often do not accurately represent its complexity. Bioprinting combines cells and biomaterials to create 3D structures that replicate the native tissue environment and can be used as a tool in disease modeling or drug screening.
METHODS: This work differentiated both healthy and diseased patient-derived human induced pluripotent stems cells (hiPSCs) into neural progenitor cells (NPCs) that were bioprinted using the Aspect RX1 microfluidic printer into dome-shaped constructs. The combination of cells, bioink, and puromorphamine (puro)-releasing microspheres were used to mimic the in vivo environment and direct the differentiation of the NPCs into basal forebrain-resembling cholinergic neurons (BFCN). These tissue models were then characterized for cell viability, immunocytochemistry, and electrophysiology to evaluate their functionality and physiology for use as disease-specific neural models.
RESULTS: Tissue models were successfully bioprinted and the cells were viable for analysis after 30- and 45-day cultures. The neuronal and cholinergic markers β-tubulin III (Tuj1), forkhead box G1 (FOXG1), and choline acetyltransferase (ChAT) were identified as well as the AD markers amyloid beta and tau. Further, immature electrical activity was observed when the cells were excited with potassium chloride and acetylcholine.
CONCLUSIONS: This work shows the successful development of bioprinted tissue models incorporating patient derived hiPSCs. Such models can potentially be used as a tool to screen promising drug candidates for treating AD. Further, this model could be used to increase the understanding of AD progression. The use of patient derived cells also shows the potential of this model for use in personalized medicine applications.

Keywords:  3D bioprinting; Alzheimer’s disease; Bioink; Microspheres; Neural tissue; Stem cells

DOI:  https://doi.org/10.1186/s42234-023-00112-7
Biofabrication. 2023 May 24.

Internally crosslinked alginate-based bioinks for the fabrication of in vitro hepatic tissue models.

Giuseppe Guagliano, Cristina Volpini, Jacopo Camilletti, Francesca Donnaloja, Francesco Briatico-Vangosa, Livia Visai, Paola Petrini.

  Bioprinting is a key technique to fabricate cell-laden volumetric constructs with controlled geometry. It can be used not only to replicate the architecture of a target organ but also to produce shapes that allow for the mimicry, in vitro, of specific desired features. Among the various materials suitable to be processed with this technique, sodium alginate is currently considered one of the most appealing because of its versatility. To date, the most widespread strategies to print alginate-based bioinks exploit external gelation as a primary process, by directly extruding the hydrogel-precursor solution into a crosslinking bath or within a sacrificial crosslinking hydrogel, where the gelation takes place. In this work, we describe the print optimization and the processing of Hep3Gel: an internally crosslinked alginate and ECM-based bioink for the production of volumetric hepatic tissue models. We adopted an unconventional strategy, by moving from the reproduction of the geometry and the architecture of liver tissue to the use of bioprinting to fabricate structures that can promote a high degree of oxygenation, as is the case with hepatic tissue. To this end, the design of structures was optimized by employing computational methods. The printability of the bioink was then studied and optimized through a combination of different a priori and a posteriori analyses. We produced 14-layered constructs, thus highlighting the possibility to exploit internal gelation alone to directly print self-standing structures with finely controlled viscoelastic properties. Constructs loaded with HepG2 cells were successfully printed and cultured in static conditions for up to 12 days, underlining the suitability of Hep3Gel to support mid/long-term cultures.

Keywords:  Biofabrication; Extracellular matrix; Extrusion bioprinting; HepG2; Liver model

DOI:  https://doi.org/10.1088/1758-5090/acd872
Bioengineering (Basel). 2023 May 10. pii: 571. [Epub ahead of print]10(5):

In Vitro Bone Differentiation of 3D Microsphere from Dental Pulp-Mesenchymal Stem Cells.

Iñigo Gaitán-Salvatella, Patricia González-Alva, Juan José Montesinos, Marco Antonio Alvarez-Perez.

  Bone defects lead to the structural loss of normal architecture, and those in the field of bone tissue engineering are searching for new alternatives to aid bone regeneration. Dental pulp-mesenchymal stem cells (DP-MSC) could provide a promising alternative to repair bone defects, principally due to their multipotency and capacity to fabricate three-dimensional (3D) spheroids. The present study aimed to characterize the 3D DP-MSC microsphere and the osteogenic differentiation capacity potential cultured by a magnetic levitation system. To achieve this, the 3D DP-MSC microsphere was grown for 7, 14, and 21 days in an osteoinductive medium and compared to 3D human fetal osteoblast (hFOB) microspheres by examining the morphology, proliferation, osteogenesis, and colonization onto PLA fiber spun membrane. Our results showed good cell viability for both 3D microspheres with an average diameter of 350 μm. The osteogenesis examination of the 3D DP-MSC microsphere revealed the lineage commitment, such as the hFOB microsphere, as evidenced by ALP activity, the calcium content, and the expression of osteoblastic markers. Finally, the evaluation of the surface colonization exhibited similar patterns of cell-spreading over the fibrillar membrane. Our study demonstrated the feasibility of forming a 3D DP-MSC microsphere structure and the cell-behavior response as a strategy for the applications of bone tissue guiding.

Keywords:  3D cell culture; alp activity; biocompatibility; bone tissue engineering; cellular spheroid

DOI:  https://doi.org/10.3390/bioengineering10050571
Materials (Basel). 2023 May 11. pii: 3676. [Epub ahead of print]16(10):

Human Ovarian Follicular Fluid Mesenchymal Stem Cells Express Osteogenic Markers When Cultured on Bioglass 58S-Coated Titanium Scaffolds.

Federica Riva, Nora Bloise, Claudia Omes, Gabriele Ceccarelli, Lorenzo Fassina, Rossella Elena Nappi, Livia Visai.

  Recent studies have reported that stem cells (human follicular fluid mesenchymal stem cells or hFF-MSCs) are present in ovarian follicular fluid (hFF) and that they have a proliferative and differentiative potential which is similar to that of MSCs derived from other adult tissue. These mesenchymal stem cells, isolated from human follicular fluid waste matter discarded after retrieval of oocytes during the IVF process, constitute another, as yet unutilized, source of stem cell materials. There has been little work on the compatibility of these hFF-MSCs with scaffolds useful for bone tissue engineering applications and the aim of this study was to evaluate the osteogenic capacity of hFF-MSCs seeded on bioglass 58S-coated titanium and to provide an assessment of their suitability for bone tissue engineering purposes. Following a chemical and morphological characterization with scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), cell viability, morphology and expression of specific osteogenic markers were examined after 7 and 21 days of culture. The hFF-MSCs seeded on bioglass and cultured with osteogenic factors, when compared with those seeded on tissue culture plate or on uncoated titanium, exhibited enhanced cell viability and osteogenic differentiation, as reflected by increased calcium deposition and increased ALP activity with expression and production of bone-related proteins. Taken together, these results demonstrate that MSCs from human follicular fluid waste materials can be easily cultured in titanium scaffolds coated with bioglass, having osteoinductive properties. This process has significant potential for regenerative medicine applications and indicates that hFF-MSCs may be a valid alternative to hBM-MSC cells in experimental models in bone tissue engineering.

Keywords:  bioglass–titanium; biomaterials; bone tissue engineering; human ovarian follicular fluid (hFF) mesenchymal stem cells (MSCs); osteogenic differentiation

DOI:  https://doi.org/10.3390/ma16103676