Trends in Decellularized Extracellular Matrix Bioinks for 3D Printing: Inspiring a new Kind of Medicine

Abstract: The promise of regenerative medicine and tissue engineering is founded on the ability to regenerate diseased or damaged tissues and organs into functional tissues and organs or the creation of new tissues and organs altogether. In theory, all damaged and diseased tissues and organs can be regenerated or created using different configurations and combinations of extracellular matrix, cells and inductive biomolecules. Currently, regenerative medicine and tissue engineering can allow the improvement of patients’ quality of life through availing novel treatment options. Tissues and organs have a specific ECM, with specific proteins and factors released by cells residing within the local microenvironment. The coupling of regenerative medicine and tissue engineering field with 3D printing is revolutionizing the treatment of patients in a huge way. 3D bioprinting allows the proper placement of cells and ECMs, allowing the recapitulation of native microenvironments of tissues and organs. 3D bioprinting utilizes different bioinks made up of different formulations of ECM/biomaterials, biomolecules and even cells. The choice of the bioink used during 3D bioprinting is very important as properties such as printability, compatibility and physical strength influence the final construct printed. The extracellular matrix (ECM) provides both physical and mechanical microenvironment needed by cells to survive and proliferate. Decellularized ECM bioink contains biochemical cues from the original native ECM and also the right proportions of ECM proteins. Different techniques and characterization methods are used to derive bioinks from several tissues and organs and to evaluate their quality. This review discusses the uses of decellularized ECM bioinks and argues that they represent the most biomimetic bioinks available. In addition, we briefly discuss some polymer-based bioinks utilized in 3D bioprinting.

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Recent Trends in Decellularized Extracellular Matrix Bioinks for 3D Printing: An Updated Review

International Journal of Molecular Sciences ◽

10.3390/ijms20184628 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4628 ◽

Cited By ~ 37

Author(s):

Kevin Dzobo ◽

Keolebogile Shirley Caroline M. Motaung ◽

Adetola Adesida

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

3D Printing ◽

Regenerative Medicine ◽

Treatment Options ◽

3D Bioprinting ◽

Characterization Methods ◽

Physical Strength ◽

Decellularized Extracellular Matrix ◽

The Right

The promise of regenerative medicine and tissue engineering is founded on the ability to regenerate diseased or damaged tissues and organs into functional tissues and organs or the creation of new tissues and organs altogether. In theory, damaged and diseased tissues and organs can be regenerated or created using different configurations and combinations of extracellular matrix (ECM), cells, and inductive biomolecules. Regenerative medicine and tissue engineering can allow the improvement of patients’ quality of life through availing novel treatment options. The coupling of regenerative medicine and tissue engineering with 3D printing, big data, and computational algorithms is revolutionizing the treatment of patients in a huge way. 3D bioprinting allows the proper placement of cells and ECMs, allowing the recapitulation of native microenvironments of tissues and organs. 3D bioprinting utilizes different bioinks made up of different formulations of ECM/biomaterials, biomolecules, and even cells. The choice of the bioink used during 3D bioprinting is very important as properties such as printability, compatibility, and physical strength influence the final construct printed. The extracellular matrix (ECM) provides both physical and mechanical microenvironment needed by cells to survive and proliferate. Decellularized ECM bioink contains biochemical cues from the original native ECM and also the right proportions of ECM proteins. Different techniques and characterization methods are used to derive bioinks from several tissues and organs and to evaluate their quality. This review discusses the uses of decellularized ECM bioinks and argues that they represent the most biomimetic bioinks available. In addition, we briefly discuss some polymer-based bioinks utilized in 3D bioprinting.

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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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3D Bioprinting at the Frontier of Regenerative Medicine, Pharmaceutical, and Food Industries

Frontiers in Medical Technology ◽

10.3389/fmedt.2020.607648 ◽

2021 ◽

Vol 2 ◽

Author(s):

Qasem Ramadan ◽

Mohammed Zourob

Keyword(s):

Tissue Engineering ◽

3D Printing ◽

Regenerative Medicine ◽

Production Process ◽

Paradigm Shift ◽

3D Bioprinting ◽

Printing Technology ◽

Food Industries ◽

3D Printing Technology ◽

Key Driver

3D printing technology has emerged as a key driver behind an ongoing paradigm shift in the production process of various industrial domains. The integration of 3D printing into tissue engineering, by utilizing life cells which are encapsulated in specific natural or synthetic biomaterials (e.g., hydrogels) as bioinks, is paving the way toward devising many innovating solutions for key biomedical and healthcare challenges and heralds' new frontiers in medicine, pharmaceutical, and food industries. Here, we present a synthesis of the available 3D bioprinting technology from what is found and what has been achieved in various applications and discussed the capabilities and limitations encountered in this technology.

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Applications of 3D Bioprinting in Tissue Engineering and Regenerative Medicine

Journal of Clinical Medicine ◽

10.3390/jcm10214966 ◽

2021 ◽

Vol 10 (21) ◽

pp. 4966

Author(s):

Gia Saini ◽

Nicole Segaran ◽

Joseph L. Mayer ◽

Aman Saini ◽

Hassan Albadawi ◽

...

Keyword(s):

Tissue Engineering ◽

3D Printing ◽

Regenerative Medicine ◽

Living Cells ◽

Clinical Applications ◽

3D Bioprinting ◽

Future Directions ◽

Specialized Tissue ◽

Tissue Models ◽

Functional Components

Regenerative medicine is an emerging field that centers on the restoration and regeneration of functional components of damaged tissue. Tissue engineering is an application of regenerative medicine and seeks to create functional tissue components and whole organs. Using 3D printing technologies, native tissue mimics can be created utilizing biomaterials and living cells. Recently, regenerative medicine has begun to employ 3D bioprinting methods to create highly specialized tissue models to improve upon conventional tissue engineering methods. Here, we review the use of 3D bioprinting in the advancement of tissue engineering by describing the process of 3D bioprinting and its advantages over other tissue engineering methods. Materials and techniques in bioprinting are also reviewed, in addition to future clinical applications, challenges, and future directions of the field.

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Crosslinker-free silk/decellularized extracellular matrix porous bioink for 3D bioprinting-based cartilage tissue engineering

Materials Science and Engineering C ◽

10.1016/j.msec.2020.111388 ◽

2021 ◽

Vol 118 ◽

pp. 111388

Author(s):

Xiao Zhang ◽

Yang Liu ◽

Chunyang Luo ◽

Chenjun Zhai ◽

Zuxi Li ◽

...

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

3D Bioprinting ◽

Decellularized Extracellular Matrix

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Editorial for the Special Issue on 3D Printing for Tissue Engineering and Regenerative Medicine

Micromachines ◽

10.3390/mi11040366 ◽

2020 ◽

Vol 11 (4) ◽

pp. 366 ◽

Cited By ~ 2

Author(s):

Vahid Serpooshan ◽

Murat Guvendiren

Keyword(s):

Tissue Engineering ◽

Additive Manufacturing ◽

3D Printing ◽

Regenerative Medicine ◽

Three Dimensional ◽

Living Cells ◽

3D Bioprinting ◽

Special Issue ◽

3D Structures ◽

Manufacturing Techniques

Three-dimensional (3D) bioprinting uses additive manufacturing techniques to fabricate 3D structures consisting of heterogenous selections of living cells, biomaterials, and active biomolecules [...]

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Tunable Human Myocardium Derived Decellularized Extracellular Matrix for 3D Bioprinting and Cardiac Tissue Engineering

Gels ◽

10.3390/gels7020070 ◽

2021 ◽

Vol 7 (2) ◽

pp. 70

Author(s):

Gozde Basara ◽

S. Gulberk Ozcebe ◽

Bradley W. Ellis ◽

Pinar Zorlutuna

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Extracellular Matrix ◽

Connexin 43 ◽

Cardiac Tissue ◽

Myocardial Infarct ◽

Cardiac Tissue Engineering ◽

3D Bioprinting ◽

Decellularized Extracellular Matrix ◽

Order Of Magnitude

The generation of 3D tissue constructs with multiple cell types and matching mechanical properties remains a challenge in cardiac tissue engineering. Recently, 3D bioprinting has become a powerful tool to achieve these goals. Decellularized extracellular matrix (dECM) is a common scaffold material due to providing a native biochemical environment. Unfortunately, dECM’s low mechanical stability prevents usage for bioprinting applications alone. In this study, we developed bioinks composed of decellularized human heart ECM (dhECM) with either gelatin methacryloyl (GelMA) or GelMA-methacrylated hyaluronic acid (MeHA) hydrogels dual crosslinked with UV light and microbial transglutaminase (mTGase). We characterized the bioinks’ mechanical, rheological, swelling, printability, and biocompatibility properties. Composite GelMA–MeHA–dhECM (GME) hydrogels demonstrated improved mechanical properties by an order of magnitude compared to the GelMA–dhECM (GE) hydrogels. All hydrogels were extrudable and compatible with human induced pluripotent stem cell derived cardiomyocytes (iCMs) and human cardiac fibroblasts (hCFs). Tissue-like beating of the printed constructs with striated sarcomeric alpha-actinin and connexin 43 expression was observed. The order of magnitude difference between the elastic modulus of these hydrogel composites offers applications in in vitro modeling of the myocardial infarct boundary. Here, as a proof of concept, we created an infarct boundary region with control over the mechanical properties along with the cellular and macromolecular content through printing iCMs with GE bioink and hCFs with GME bioink.

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Tunable human myocardium derived decellularized extracellular matrix for 3D bioprinting and cardiac tissue engineering

10.1101/2021.03.30.437600 ◽

2021 ◽

Author(s):

Gozde Basara ◽

S. Gulberk Ozcebe ◽

Bradley W. Ellis ◽

Pinar Zorlutuna

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Extracellular Matrix ◽

Connexin 43 ◽

Cardiac Tissue ◽

Myocardial Infarct ◽

Cardiac Tissue Engineering ◽

3D Bioprinting ◽

Decellularized Extracellular Matrix ◽

Order Of Magnitude

AbstractThe generation of 3D tissue constructs with multiple cell types and matching mechanical properties remains a challenge in cardiac tissue engineering. Recently, 3D bioprinting has become a powerful tool to achieve these goals. Decellularized extracellular matrix (dECM) is a common scaffold material due to providing a native biochemical environment. Unfortunately, dECM’s low mechanical stability prevents usage for bioprinting applications alone. In this study, we developed bioinks composed of decellularized human heart ECM (dhECM) with either gelatin methacryloyl (GelMA) or GelMA- methacrylated hyaluronic acid (MeHA) hydrogels dual crosslinked with UV light and microbial Transglutaminase (mTGase). We characterized the bioinks’ mechanical, rheological, swelling, printability and biocompatibility properties. Composite GelMA-MeHA-dhECM (GME) hydrogels demonstrated improved mechanical properties by an order of magnitude, compared to GelMA-dhECM (GE) hydrogels. All hydrogels were extrudable and compatible with human induced pluripotent stem cells derived cardiomyocytes (iCMs) and human cardiac fibroblasts (hCFs). Tissue-like beating of the printed constructs with striated sarcomeric alpha-actinin and Connexin 43 expression was observed. The order of magnitude difference between the elastic modulus of these hydrogel composites offers applications in in vitro modelling of the myocardial infarct boundary. Here, as a proof of concept, we created an infarct boundary region with control over mechanical properties along with cellular and macromolecular content through printing iCMs with GE bioink and hCFs with GME bioink.

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