3D Bioprinting in Tissue Engineering for Medical Applications: The Classic and the Hybrid

Three-dimensional (3D) printing, as one of the most popular recent additive manufacturing processes, has shown strong potential for the fabrication of biostructures in the field of tissue engineering, most notably for bones, orthopedic tissues, and associated organs. Desirable biological, structural, and mechanical properties can be achieved for 3D-printed constructs with a proper selection of biomaterials and compatible bioprinting methods, possibly even while combining additive and conventional manufacturing (AM and CM) procedures. However, challenges remain in the need for improved printing resolution (especially at the nanometer level), speed, and biomaterial compatibilities, and a broader range of suitable 3D-printed materials. This review provides an overview of recent advances in the development of 3D bioprinting techniques, particularly new hybrid 3D bioprinting technologies for combining the strengths of both AM and CM, along with a comprehensive set of material selection principles, promising medical applications, and limitations and future prospects.

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The Fabrication of Tissue Engineering Scaffolds by Inkjet Printing Technology

Materials Science Forum ◽

10.4028/www.scientific.net/msf.934.129 ◽

2018 ◽

Vol 934 ◽

pp. 129-133 ◽

Cited By ~ 1

Author(s):

Chao Fan Lv ◽

Li Ya Zhu ◽

Jian Ping Shi ◽

Zong An Li ◽

Wen Lai Tang ◽

...

Keyword(s):

Tissue Engineering ◽

Sodium Alginate ◽

Inkjet Printing ◽

Three Dimensional ◽

3D Bioprinting ◽

Tissue Engineering Scaffolds ◽

Printing Technology ◽

3D Printed ◽

Inkjet Printing Technology ◽

Alginate Scaffold

Three-dimensional (3D) printing has been playing an important role in diverse areas in medicine. In order to promote the development of tissue engineering, this study attempts to fabricate tissue engineering scaffolds using the inkjet printing technology. Sodium alginate, exhibiting similar properties to the native human extracellular matrix (ECM), was used as bioink. The jetted fluid of sodium alginate would be gelatinized when printed into the calcium chloride solution. The characteristics of the 3D-printed sodium alginate scaffold were systematically measured and analyzed. The results show that, the pore size, porosity and degradation property of these scaffolds could be well controlled. This study indicates the capability of 3D bioprinting technology for preparing tissue engineering scaffolds.

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3D Bioprinting of Vascularized Tissues for in vitro and in vivo Applications

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.664188 ◽

2021 ◽

Vol 9 ◽

Author(s):

Earnest P. Chen ◽

Zeren Toksoy ◽

Bruce A. Davis ◽

John P. Geibel

Keyword(s):

Tissue Engineering ◽

Drug Testing ◽

Rapid Development ◽

Three Dimensional ◽

3D Bioprinting ◽

Vascular Networks ◽

Main Challenge ◽

3D Printed

With a limited supply of organ donors and available organs for transplantation, the aim of tissue engineering with three-dimensional (3D) bioprinting technology is to construct fully functional and viable tissue and organ replacements for various clinical applications. 3D bioprinting allows for the customization of complex tissue architecture with numerous combinations of materials and printing methods to build different tissue types, and eventually fully functional replacement organs. The main challenge of maintaining 3D printed tissue viability is the inclusion of complex vascular networks for nutrient transport and waste disposal. Rapid development and discoveries in recent years have taken huge strides toward perfecting the incorporation of vascular networks in 3D printed tissue and organs. In this review, we will discuss the latest advancements in fabricating vascularized tissue and organs including novel strategies and materials, and their applications. Our discussion will begin with the exploration of printing vasculature, progress through the current statuses of bioprinting tissue/organoids from bone to muscles to organs, and conclude with relevant applications for in vitro models and drug testing. We will also explore and discuss the current limitations of vascularized tissue engineering and some of the promising future directions this technology may bring.

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Development of three-dimensional printing filaments based on poly(lactic acid)/hydroxyapatite composites with potential for tissue engineering

Journal of Composite Materials ◽

10.1177/0021998320988568 ◽

2021 ◽

pp. 002199832098856

Author(s):

Marcela Piassi Bernardo ◽

Bruna Cristina Rodrigues da Silva ◽

Luiz Henrique Capparelli Mattoso

Keyword(s):

Tissue Engineering ◽

Lactic Acid ◽

Fused Deposition Modeling ◽

Three Dimensional ◽

Poly Lactic Acid ◽

Scanning Calorimetry ◽

Three Dimensional Printing ◽

Fused Deposition ◽

Deposition Modeling ◽

3D Printed

Injured bone tissues can be healed with scaffolds, which could be manufactured using the fused deposition modeling (FDM) strategy. Poly(lactic acid) (PLA) is one of the most biocompatible polymers suitable for FDM, while hydroxyapatite (HA) could improve the bioactivity of scaffold due to its chemical composition. Therefore, the combination of PLA/HA can create composite filaments adequate for FDM and with high osteoconductive and osteointegration potentials. In this work, we proposed a different approache to improve the potential bioactivity of 3D printed scaffolds for bone tissue engineering by increasing the HA loading (20-30%) in the PLA composite filaments. Two routes were investigated regarding the use of solvents in the filament production. To assess the suitability of the FDM-3D printing process, and the influence of the HA content on the polymer matrix, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) were performed. The HA phase content of the composite filaments agreed with the initial composite proportions. The wettability of the 3D printed scaffolds was also increased. It was shown a greener route for obtaining composite filaments that generate scaffolds with properties similar to those obtained by the solvent casting, with high HA content and great potential to be used as a bone graft.

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Three-Dimensional Printing of Hydroxyapatite Composites for Biomedical Application

Crystals ◽

10.3390/cryst11040353 ◽

2021 ◽

Vol 11 (4) ◽

pp. 353

Author(s):

Yanting Han ◽

Qianqian Wei ◽

Pengbo Chang ◽

Kehui Hu ◽

Oseweuba Valentine Okoro ◽

...

Keyword(s):

Tissue Engineering ◽

3D Printing ◽

Biomedical Application ◽

Three Dimensional ◽

Antibacterial Properties ◽

Natural Polymers ◽

Three Dimensional Printing ◽

3D Printed ◽

Dental Applications ◽

Hard Tissue Engineering

Hydroxyapatite (HA) and HA-based nanocomposites have been recognized as ideal biomaterials in hard tissue engineering because of their compositional similarity to bioapatite. However, the traditional HA-based nanocomposites fabrication techniques still limit the utilization of HA in bone, cartilage, dental, applications, and other fields. In recent years, three-dimensional (3D) printing has been shown to provide a fast, precise, controllable, and scalable fabrication approach for the synthesis of HA-based scaffolds. This review therefore explores available 3D printing technologies for the preparation of porous HA-based nanocomposites. In the present review, different 3D printed HA-based scaffolds composited with natural polymers and/or synthetic polymers are discussed. Furthermore, the desired properties of HA-based composites via 3D printing such as porosity, mechanical properties, biodegradability, and antibacterial properties are extensively explored. Lastly, the applications and the next generation of HA-based nanocomposites for tissue engineering are discussed.

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Three-dimensionally printed polycaprolactone/multicomponent bioactive glass scaffolds for potential application in bone tissue engineering

Biomedical glasses ◽

10.1515/bglass-2020-0006 ◽

2020 ◽

Vol 6 (1) ◽

pp. 57-69

Author(s):

Amirhosein Fathi ◽

Farzad Kermani ◽

Aliasghar Behnamghader ◽

Sara Banijamali ◽

Masoud Mozafari ◽

...

Keyword(s):

Tissue Engineering ◽

3D Printing ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Three Dimensional ◽

Layer By Layer ◽

Composite Scaffolds ◽

3D Printed ◽

Co Doped

AbstractOver the last years, three-dimensional (3D) printing has been successfully applied to produce suitable substitutes for treating bone defects. In this work, 3D printed composite scaffolds of polycaprolactone (PCL) and strontium (Sr)- and cobalt (Co)-doped multi-component melt-derived bioactive glasses (BGs) were prepared for bone tissue engineering strategies. For this purpose, 30% of as-prepared BG particles (size <38 μm) were incorporated into PCL, and then the obtained composite mix was introduced into a 3D printing machine to fabricate layer-by-layer porous structures with the size of 12 × 12 × 2 mm3.The scaffolds were fully characterized through a series of physico-chemical and biological assays. Adding the BGs to PCL led to an improvement in the compressive strength of the fabricated scaffolds and increased their hydrophilicity. Furthermore, the PCL/BG scaffolds showed apatite-forming ability (i.e., bioactivity behavior) after being immersed in simulated body fluid (SBF). The in vitro cellular examinations revealed the cytocompatibility of the scaffolds and confirmed them as suitable substrates for the adhesion and proliferation of MG-63 osteosarcoma cells. In conclusion, 3D printed composite scaffolds made of PCL and Sr- and Co-doped BGs might be potentially-beneficial bone replacements, and the achieved results motivate further research on these materials.

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Hydrogel-Based Bioinks for Three-Dimensional Bioprinting: Patent Analysis

Materials Proceedings ◽

10.3390/iocps2021-11239 ◽

2021 ◽

Vol 7 (1) ◽

pp. 3

Author(s):

Ahmed Fatimi

Keyword(s):

Tissue Engineering ◽

Detailed Analysis ◽

State Of The Art ◽

Three Dimensional ◽

Patent Analysis ◽

The State ◽

Driving Factors ◽

3D Bioprinting ◽

Preparation Methods

There are a variety of hydrogel-based bioinks commonly used in three-dimensional bioprinting. In this study, in the form of patent analysis, the state of the art has been reviewed by introducing what has been patented in relation to hydrogel-based bioinks. Furthermore, a detailed analysis of the patentability of the used hydrogels, their preparation methods and their formulations, as well as the 3D bioprinting process using hydrogels, have been provided by determining publication years, jurisdictions, inventors, applicants, owners, and classifications. The classification of patents reveals that most inventions intended for hydrogels used as materials for prostheses or for coating prostheses are characterized by their function or properties Knowledge clusters and expert driving factors show that biomaterials, tissue engineering, and biofabrication research is concentrated in the most patents.

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Three-dimensional (3D) printed scaffold and material selection for bone repair

Acta Biomaterialia ◽

10.1016/j.actbio.2018.11.039 ◽

2019 ◽

Vol 84 ◽

pp. 16-33 ◽

Cited By ~ 89

Author(s):

Lei Zhang ◽

Guojing Yang ◽

Blake N. Johnson ◽

Xiaofeng Jia

Keyword(s):

Bone Repair ◽

Material Selection ◽

Three Dimensional ◽

3D Printed ◽

Selection For

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Using Spheroids as Building Blocks Towards 3D Bioprinting of Tumor Microenvironment

International Journal of Bioprinting ◽

10.18063/ijb.v7i4.444 ◽

2021 ◽

Vol 7 (4) ◽

pp. 444

Author(s):

Pei Zhuang ◽

Yi-Hua Chiang ◽

Maria Serafim Fernanda ◽

Mei He

Keyword(s):

Tumor Microenvironment ◽

Prediction Models ◽

Three Dimensional ◽

3D Culture ◽

Building Blocks ◽

3D Bioprinting ◽

Multicellular Spheroids ◽

Tumor Models ◽

3D Printed

Cancer still ranks as a leading cause of mortality worldwide. Although considerable efforts have been dedicated to anticancer therapeutics, progress is still slow, partially due to the absence of robust prediction models. Multicellular tumor spheroids, as a major three-dimensional (3D) culture model exhibiting features of avascular tumors, gained great popularity in pathophysiological studies and high throughput drug screening. However, limited control over cellular and structural organization is still the key challenge in achieving in vivo like tissue microenvironment. 3D bioprinting has made great strides toward tissue/organ mimicry, due to its outstanding spatial control through combining both cells and materials, scalability, and reproducibility. Prospectively, harnessing the power from both 3D bioprinting and multicellular spheroids would likely generate more faithful tumor models and advance our understanding on the mechanism of tumor progression. In this review, the emerging concept on using spheroids as a building block in 3D bioprinting for tumor modeling is illustrated. We begin by describing the context of the tumor microenvironment, followed by an introduction of various methodologies for tumor spheroid formation, with their specific merits and drawbacks. Thereafter, we present an overview of existing 3D printed tumor models using spheroids as a focus. We provide a compilation of the contemporary literature sources and summarize the overall advancements in technology and possibilities of using spheroids as building blocks in 3D printed tissue modeling, with a particular emphasis on tumor models. Future outlooks about the wonderous advancements of integrated 3D spheroidal printing conclude this review.

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3D Printing of Thermo-Sensitive Drugs

Pharmaceutics ◽

10.3390/pharmaceutics13091524 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1524

Author(s):

Sadikalmahdi Abdella ◽

Souha H. Youssef ◽

Franklin Afinjuomo ◽

Yunmei Song ◽

Paris Fouladian ◽

...

Keyword(s):

3D Printing ◽

Three Dimensional ◽

Fused Deposition Modelling ◽

Future Directions ◽

Digital Light Processing ◽

Fused Deposition ◽

Printing Technique ◽

3D Printed ◽

Semi Solid ◽

Selection Of

Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations.

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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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