Extracellular Matrix/Amorphous Magnesium Phosphate Bioink for 3D Bioprinting of Craniomaxillofacial Bone Tissue

Unlike the conventional techniques used to construct a tissue scaffolding, three-dimensional (3D) bioprinting technology enables fabrication of a porous structure with complex and diverse geometries, which facilitate evenly distributed cells and orderly release of signal factors. To date, a range of cell-laden materials, such as natural or synthetic polymers, have been deployed by the 3D bioprinting technique to construct the scaffolding systems and regenerate substitutes for the natural extracellular matrix (ECM). Four-dimensional (4D) bioprinting technology has attracted much attention lately because it aims to accommodate the dynamic structural and functional transformations of scaffolds. However, there remain challenges to meet the technical requirements in terms of suitable processability of the bioink formulations, desired mechanical properties of the hydrogel implants, and cell-guided functionality of the biomaterials. Recent bioprinting techniques are reviewed in this article, discussing strategies for hydrogel-based bioinks to mimic native bone tissue-like extracellular matrix environment, including properties of bioink formulations required for bioprinting, structure requirements, and preparation of tough hydrogel scaffolds. Stimulus mechanisms that are commonly used to trigger the dynamic structural and functional transformations of the scaffold are analyzed. At the end, we highlighted the current challenges and possible future avenues of smart hydrogel-based bioink/scaffolds for bone tissue regeneration.

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3D-Bioprinting Strategies Based on In Situ Bone-Healing Mechanism for Vascularized Bone Tissue Engineering

Micromachines ◽

10.3390/mi12030287 ◽

2021 ◽

Vol 12 (3) ◽

pp. 287

Author(s):

Ye Lin Park ◽

Kiwon Park ◽

Jae Min Cha

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Bone Healing ◽

Critical Size ◽

Current Knowledge ◽

3D Bioprinting ◽

The Past ◽

Regeneration Processes

Over the past decades, a number of bone tissue engineering (BTE) approaches have been developed to address substantial challenges in the management of critical size bone defects. Although the majority of BTE strategies developed in the laboratory have been limited due to lack of clinical relevance in translation, primary prerequisites for the construction of vascularized functional bone grafts have gained confidence owing to the accumulated knowledge of the osteogenic, osteoinductive, and osteoconductive properties of mesenchymal stem cells and bone-relevant biomaterials that reflect bone-healing mechanisms. In this review, we summarize the current knowledge of bone-healing mechanisms focusing on the details that should be embodied in the development of vascularized BTE, and discuss promising strategies based on 3D-bioprinting technologies that efficiently coalesce the abovementioned main features in bone-healing systems, which comprehensively interact during the bone regeneration processes.

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Artificial Tumor Microenvironments in Neuroblastoma

Cancers ◽

10.3390/cancers13071629 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1629

Author(s):

Colin H. Quinn ◽

Andee M. Beierle ◽

Elizabeth A. Beierle

Keyword(s):

Extracellular Matrix ◽

Three Dimensional ◽

Therapeutic Interventions ◽

3D Bioprinting ◽

Culture Studies ◽

In Vivo Models ◽

Novel Treatments ◽

Tumor Microenvironments ◽

Novel Approach

In the quest to advance neuroblastoma therapeutics, there is a need to have a deeper understanding of the tumor microenvironment (TME). From extracellular matrix proteins to tumor associated macrophages, the TME is a robust and diverse network functioning in symbiosis with the solid tumor. Herein, we review the major components of the TME including the extracellular matrix, cytokines, immune cells, and vasculature that support a more aggressive neuroblastoma phenotype and encumber current therapeutic interventions. Contemporary treatments for neuroblastoma are the result of traditional two-dimensional culture studies and in vivo models that have been translated to clinical trials. These pre-clinical studies are costly, time consuming, and neglect the study of cofounding factors such as the contributions of the TME. Three-dimensional (3D) bioprinting has become a novel approach to studying adult cancers and is just now incorporating portions of the TME and advancing to study pediatric solid. We review the methods of 3D bioprinting, how researchers have included TME pieces into the prints, and highlight present studies using neuroblastoma. Ultimately, incorporating the elements of the TME that affect neuroblastoma responses to therapy will improve the development of innovative and novel treatments. The use of 3D bioprinting to achieve this aim will prove useful in developing optimal therapies for children with neuroblastoma.

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Bio-inks for 3D bioprinting: recent advances and future prospects

Polymer Chemistry ◽

10.1039/c7py00826k ◽

2017 ◽

Vol 8 (31) ◽

pp. 4451-4471 ◽

Cited By ~ 106

Author(s):

Ilze Donderwinkel ◽

Jan C. M. van Hest ◽

Neil R. Cameron

Keyword(s):

Extracellular Matrix ◽

Three Dimensional ◽

Extracellular Matrix Proteins ◽

Matrix Proteins ◽

Cell Aggregates ◽

3D Bioprinting ◽

Future Prospects ◽

Printing Inks ◽

Polymer Bead ◽

Polymeric Hydrogels

In the last decade, interest in the field of three-dimensional (3D) bioprinting has increased enormously. This review describes all the currently used bio-printing inks, including polymeric hydrogels, polymer bead microcarriers, cell aggregates and extracellular matrix proteins.

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Cell-secreted extracellular matrix, independent of cell source, promotes the osteogenic differentiation of human stromal vascular fraction

Journal of Materials Chemistry B ◽

10.1039/c7tb02787g ◽

2018 ◽

Vol 6 (24) ◽

pp. 4104-4115 ◽

Cited By ~ 15

Author(s):

Jenna N. Harvestine ◽

Hakan Orbay ◽

Jonathan Y. Chen ◽

David E. Sahar ◽

J. Kent Leach

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Bone Tissue Engineering ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Stromal Vascular Fraction ◽

Cell Source

Cell-secreted extracellular matrix potentiates osteogenic differentiation by stromal vascular fraction for bone tissue engineering.

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Fabrication of 3D Printing Scaffold with Porcine Skin Decellularized Bio-Ink for Soft Tissue Engineering

Materials ◽

10.3390/ma13163522 ◽

2020 ◽

Vol 13 (16) ◽

pp. 3522

Author(s):

Su Jeong Lee ◽

Jun Hee Lee ◽

Jisun Park ◽

Wan Doo Kim ◽

Su A Park

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

3D Printing ◽

Three Dimensional ◽

3D Bioprinting ◽

Research Groups ◽

Porcine Skin ◽

Alginate Hydrogel ◽

Chemical Treatments ◽

Soft Tissue Engineering

Recently, many research groups have investigated three-dimensional (3D) bioprinting techniques for tissue engineering and regenerative medicine. The bio-ink used in 3D bioprinting is typically a combination of synthetic and natural materials. In this study, we prepared bio-ink containing porcine skin powder (PSP) to determine rheological properties, biocompatibility, and extracellular matrix (ECM) formation in cells in PSP-ink after 3D printing. PSP was extracted without cells by mechanical, enzymatic, and chemical treatments of porcine dermis tissue. Our developed PSP-containing bio-ink showed enhanced printability and biocompatibility. To identify whether the bio-ink was printable, the viscosity of bio-ink and alginate hydrogel was analyzed with different concentration of PSP. As the PSP concentration increased, viscosity also increased. To assess the biocompatibility of the PSP-containing bio-ink, cells mixed with bio-ink printed structures were measured using a live/dead assay and WST-1 assay. Nearly no dead cells were observed in the structure containing 10 mg/mL PSP-ink, indicating that the amounts of PSP-ink used were nontoxic. In conclusion, the proposed skin dermis decellularized bio-ink is a candidate for 3D bioprinting.

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Fabrication of Decellularized Engineered Extracellular Matrix through Bioreactor-Based Environment for Bone Tissue Engineering

ACS Omega ◽

10.1021/acsomega.0c04861 ◽

2020 ◽

Vol 5 (49) ◽

pp. 31943-31956

Author(s):

Hanieh Nokhbatolfoghahaei ◽

Zahrasadat Paknejad ◽

Mahboubeh Bohlouli ◽

Maryam Rezai Rad ◽

Pouyan Aminishakib ◽

...

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Bone Tissue Engineering ◽

Bone Tissue

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Effect of the biodegradation rate controlled by pore structures in magnesium phosphate ceramic scaffolds on bone tissue regeneration in vivo

Acta Biomaterialia ◽

10.1016/j.actbio.2016.08.039 ◽

2016 ◽

Vol 44 ◽

pp. 155-167 ◽

Cited By ~ 56

Author(s):

Ju-Ang Kim ◽

Jiwon Lim ◽

Raja Naren ◽

Hui-suk Yun ◽

Eui Kyun Park

Keyword(s):

Bone Tissue ◽

Tissue Regeneration ◽

Bone Tissue Regeneration ◽

Magnesium Phosphate ◽

Biodegradation Rate ◽

Pore Structures ◽

Rate Controlled

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Combining Innovative Bioink and Low Cell Density for the Production of 3D-Bioprinted Cartilage Substitutes: A Pilot Study

Stem Cells International ◽

10.1155/2020/2487072 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16 ◽

Cited By ~ 3

Author(s):

Christel Henrionnet ◽

Léa Pourchet ◽

Paul Neybecker ◽

Océane Messaoudi ◽

Pierre Gillet ◽

...

Keyword(s):

Gene Expression ◽

Extracellular Matrix ◽

Cell Encapsulation ◽

Type Ii Collagen ◽

Mitochondrial Activity ◽

Type Ii ◽

3D Bioprinting ◽

Matrix Synthesis ◽

M Cell ◽

Low Concentration

3D bioprinting offers interesting opportunities for 3D tissue printing by providing living cells with appropriate scaffolds with a dedicated structure. Biological advances in bioinks are currently promising for cell encapsulation, particularly that of mesenchymal stem cells (MSCs). We present herein the development of cartilage implants by 3D bioprinting that deliver MSCs encapsulated in an original bioink at low concentration. 3D-bioprinted constructs (10×10×4 mm) were printed using alginate/gelatin/fibrinogen bioink mixed with human bone marrow MSCs. The influence of the bioprinting process and chondrogenic differentiation on MSC metabolism, gene profiles, and extracellular matrix (ECM) production at two different MSC concentrations (1 million or 2 million cells/mL) was assessed on day 28 (D28) by using MTT tests, real-time RT-PCR, and histology and immunohistochemistry, respectively. Then, the effect of the environment (growth factors such as TGF-β1/3 and/or BMP2 and oxygen tension) on chondrogenicity was evaluated at a 1 M cell/mL concentration on D28 and D56 by measuring mitochondrial activity, chondrogenic gene expression, and the quality of cartilaginous matrix synthesis. We confirmed the safety of bioextrusion and gelation at concentrations of 1 million and 2 million MSC/mL in terms of cellular metabolism. The chondrogenic effect of TGF-β1 was verified within the substitute on D28 by measuring chondrogenic gene expression and ECM synthesis (glycosaminoglycans and type II collagen) on D28. The 1 M concentration represented the best compromise. We then evaluated the influence of various environmental factors on the substitutes on D28 (differentiation) and D56 (synthesis). Chondrogenic gene expression was maximal on D28 under the influence of TGF-β1 or TGF-β3 either alone or in combination with BMP-2. Hypoxia suppressed the expression of hypertrophic and osteogenic genes. ECM synthesis was maximal on D56 for both glycosaminoglycans and type II collagen, particularly in the presence of a combination of TGF-β1 and BMP-2. Continuous hypoxia did not influence matrix synthesis but significantly reduced the appearance of microcalcifications within the extracellular matrix. The described strategy is very promising for 3D bioprinting by the bioextrusion of an original bioink containing a low concentration of MSCs followed by the culture of the substitutes in hypoxic conditions under the combined influence of TGF-β1 and BMP-2.

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Control of Oriented Extracellular Matrix Similar to Anisotropic Bone Microstructure

Materials Science Forum ◽

10.4028/www.scientific.net/msf.783-786.72 ◽

2014 ◽

Vol 783-786 ◽

pp. 72-77 ◽

Cited By ~ 2

Author(s):

Takayoshi Nakano ◽

Aira Matsugaki ◽

Takuya Ishimoto ◽

Mitsuharu Todai ◽

Ai Serizawa ◽

...

Keyword(s):

Extracellular Matrix ◽

Bone Tissue ◽

Bone Cells ◽

Crystal Surface ◽

Early Stage ◽

Bone Microstructure ◽

Bone Cell ◽

Collagen Fibers

Bone microstructure is dominantly composed of anisotropic extracellular matrix (ECM) in which collagen fibers and epitaxially-oriented biological apatite (BAp) crystals are preferentially aligned depending on the bone anatomical position, resulting in exerting appropriate mechanical function. The regenerative bone in bony defects is however produced without the preferential alignment of collagen fibers and the c-axis of BAp crystals, and subsequently reproduced to recover toward intact alignment. Thus, it is necessary to produce the anisotropic bone-mimetic tissue for the quick recovery of original bone tissue and the related mechanical ability in the early stage of bone regeneration. Our group is focusing on the methodology for regulating the arrangement of bone cells, the following secretion of collagen and the self-assembled mineralization by oriented BAp crystallites. Cyclic stretching in vitro to bone cells, principal-stress loading in vivo on scaffolds, step formation by slip traces on Ti single crystal, surface modification by laser induced periodic surface structure (LIPSS), anisotropic collagen substrate with the different degree of orientation, etc. can dominate bone cell arrangement and lead to the construction of the oriented ECM similar to the bone tissue architecture. This suggests that stress/strain loading, surface topography and chemical anisotropy are useful to produce bone-like microstructure in order to promote the regeneration of anisotropic bone tissue and to understand the controlling parameters for anisotropic osteogenesis induction.

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