Direct Freeform Fabrication Technique for Bio-Manufacturing of Pre-Seeded, Spatially Heterogeneous, Anatomically-Shaped Alginate Hydrogel Implants

Author(s):  
Daniel L. Cohen ◽  
Evan Malone ◽  
Hod Lipson ◽  
Lawrence J. Bonassar

A major challenge in orthopaedic tissue engineering is the generation of cell-seeded implants with structures that mimic native tissue, both in terms of anatomic geometries and intratissue cell distributions. By combining the strengths of injection molding tissue engineering with those of Solid Freeform Fabrication (SFF), three-dimensional pre-seeded implants were fabricated without custom-tooling, enabling efficient production of patient-specific implants. The incorporation of SFF technology also enables the fabrication of geometrically complex, multiple-material implants with spatially heterogeneous cell distributions that could not otherwise be produced. Using a custom-built robotic SFF platform and gel deposition tools, alginate hydrogel was used with calcium sulfate as a crosslinking agent to produce pre-seeded living implants of arbitrary geometries. The process was determined to be sterile and viable at 94±5%. The GAG production was found to be about half that of a similarly molded samples. The compressive elastic modulus was determined to be 1.462±0.113 kPa.

Author(s):  
Jin-Hyung Shim ◽  
Jong Young Kim ◽  
Kyung Shin Kang ◽  
Jung Kyu Park ◽  
Sei Kwang Hahn ◽  
...  

Tissue engineering is an interdisciplinary field that focuses on restoring and repairing tissues or organs. Cells, scaffolds, and biomolecules are recognized as three main components of tissue engineering. Solid freeform fabrication (SFF) technology is required to fabricate three-dimensional (3D) porous scaffolds to provide a 3D environment for cellular activity. SFF technology is especially advantageous for achieving a fully interconnected, porous scaffold. Bone morphogenic protein-2 (BMP-2), an important biomolecule, is widely used in bone tissue engineering to enhance bone regeneration activity. However, methods for the direct incorporation of intact BMP-2 within 3D scaffolds are rare. In this work, 3D porous scaffolds with poly(lactic-co-glycolic acid) chemically grafted hyaluronic acid (HA-PLGA), in which intact BMP-2 was directly encapsulated, were successfully fabricated using SFF technology. BMP-2 was previously protected by poly(ethylene glycol) (PEG), and the BMP-2/PEG complex was incorporated in HA-PLGA using an organic solvent. The HAPLGA/PEG/BMP-2 mixture was dissolved in chloroform and deposited via a multi-head deposition system (MHDS), one type of SFF technology, to fabricate a scaffold for tissue engineering. An additional air blower system and suction were installed in the MHDS for the solvent-based fabrication method. An in vitro evaluation of BMP-2 release was conducted, and prolonged release of intact BMP-2, for up to 28 days, was confirmed. After confirmation of advanced proliferation of pre osteoblasts, a superior differentiation effect of the HA-PLGA/PEG/BMP-2 scaffold was validated by measuring high expression levels of bone-specific markers, such as alkaline phosphatase (ALP) and osteocalcin (OC). We show that our solvent-based fabrication is a non-toxic method for restoring cellular activity. Moreover, the HAPLGA/PEG/BMP-2 scaffold was effective for bone regeneration.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7271 ◽  
Author(s):  
Wen Liao ◽  
Lin Xu ◽  
Kaijuan Wangrao ◽  
Yu Du ◽  
Qiuchan Xiong ◽  
...  

With the development of technology, tissue engineering (TE) has been widely applied in the medical field. In recent years, due to its accuracy and the demands of solid freeform fabrication in TE, three-dimensional printing, also known as additive manufacturing (AM), has been applied for biological scaffold fabrication in craniofacial and dental regeneration. In this review, we have compared several types of AM techniques and summarized their advantages and limitations. The range of printable materials used in craniofacial and dental tissue includes all the biomaterials. Thus, basic and clinical studies were discussed in this review to present the application of AM techniques in craniofacial and dental tissue and their advances during these years, which might provide information for further AM studies in craniofacial and dental TE.


2002 ◽  
Vol 758 ◽  
Author(s):  
Suman Das ◽  
Scott J. Hollister ◽  
Colleen Flanagan ◽  
Adebisi Adewunmi ◽  
Karlin Bark ◽  
...  

ABSTRACTAdvanced and novel fabrication methods are needed to build complex three-dimensional scaffolds that incorporate multiple functionally graded biomaterials with a porous internal architecture that will enable the simultaneous growth of multiple tissues, tissue interfaces and blood vessels. The aim of this research is to develop, demonstrate and characterize techniques for fabricating such scaffolds by combining solid freeform fabrication and computational design methods. When fully developed, such techniques are expected to enable the fabrication of tissue engineering scaffolds endowed with functionally graded material composition and porosity exhibiting sharp or smooth gradients. As a first step towards realizing this goal, scaffolds with periodic cellular and biomimetic architectures were designed and fabricated using selective laser sintering in Nylon-6, a biocompatible polymer. Results of bio-compatibility and in vivo implantation studies conducted on these scaffolds are reported.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Erfan Rezvani Ghomi ◽  
Saeideh Kholghi Eshkalak ◽  
Sunpreet Singh ◽  
Amutha Chinnappan ◽  
Seeram Ramakrishna ◽  
...  

Purpose The potential implications of the three-dimensional printing (3DP) technology are growing enormously in the various health-care sectors, including surgical planning, manufacturing of patient-specific implants and developing anatomical models. Although a wide range of thermoplastic polymers are available as 3DP feedstock, yet obtaining biocompatible and structurally integrated biomedical devices is still challenging owing to various technical issues. Design/methodology/approach Polyether ether ketone (PEEK) is an organic and biocompatible compound material that is recently being used to fabricate complex design geometries and patient-specific implants through 3DP. However, the thermal and rheological features of PEEK make it difficult to process through the 3DP technologies, for instance, fused filament fabrication. The present review paper presents a state-of-the-art literature review of the 3DP of PEEK for potential biomedical applications. In particular, a special emphasis has been given on the existing technical hurdles and possible technological and processing solutions for improving the printability of PEEK. Findings The reviewed literature highlighted that there exist numerous scientific and technical means which can be adopted for improving the quality features of the 3D-printed PEEK-based biomedical structures. The discussed technological innovations will help the 3DP system to enhance the layer adhesion strength, structural stability, as well as enable the printing of high-performance thermoplastics. Originality/value The content of the present manuscript will motivate young scholars and senior scientists to work in exploring high-performance thermoplastics for 3DP applications.


Author(s):  
Lakshya P. Rathore ◽  
Naina Verma

Additive manufacturing (AM) is a novel technique that despite having been around for more than 35 years, has been underutilized. Its great advantage lies in the basic fact that it is incredibly customizable. Since its use was recognized in various fields of medicine like orthopaedics, otorhinolaryngology, ophthalmology etc, it has proved to be one of the most promising developments in most of them. Customizable orthotics, prosthetics and patient specific implants and tracheal splints are few of its advantages. And in the future too, the combination of tissue engineering with AM is believed to produce an immense change in biological tissue replacement.


Materials ◽  
2020 ◽  
Vol 13 (16) ◽  
pp. 3522
Author(s):  
Su Jeong Lee ◽  
Jun Hee Lee ◽  
Jisun Park ◽  
Wan Doo Kim ◽  
Su A Park

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.


2020 ◽  
Vol 9 (3) ◽  
pp. 832 ◽  
Author(s):  
Dave Chamo ◽  
Bilal Msallem ◽  
Neha Sharma ◽  
Soheila Aghlmandi ◽  
Christoph Kunz ◽  
...  

The use of patient-specific implants (PSIs) in craniofacial surgery is often limited due to a lack of expertise and/or production costs. Therefore, a simple and cost-efficient template-based fabrication workflow has been developed to overcome these disadvantages. The aim of this study is to assess the accuracy of PSIs made from their original templates. For a representative cranial defect (CRD) and a temporo-orbital defect (TOD), ten PSIs were made from polymethylmethacrylate (PMMA) using computer-aided design (CAD) and three-dimensional (3D) printing technology. These customized implants were measured and compared with their original 3D printed templates. The implants for the CRD revealed a root mean square (RMS) value ranging from 1.128 to 0.469 mm with a median RMS (Q1 to Q3) of 0.574 (0.528 to 0.701) mm. Those for the TOD revealed an RMS value ranging from 1.079 to 0.630 mm with a median RMS (Q1 to Q3) of 0.843 (0.635 to 0.943) mm. This study demonstrates that a highly precise duplication of PSIs can be achieved using this template-molding workflow. Thus, virtually planned implants can be accurately transferred into haptic PSIs. This workflow appears to offer a sophisticated solution for craniofacial reconstruction and continues to prove itself in daily clinical practice.


2010 ◽  
Vol 4 (4) ◽  
Author(s):  
Ibrahim T. Ozbolat ◽  
Bahattin Koc

This paper presents a computer-aided design (CAD) of 3D porous tissue scaffolds with spatial control of encapsulated biomolecule distributions. A localized control of encapsulated biomolecule distribution over 3D structures is proposed to control release kinetics spatially for tissue engineering and drug release. Imaging techniques are applied to explore distribution of microspheres over porous structures. Using microspheres in this study represents a framework for modeling the distribution characteristics of encapsulated proteins, growth factors, cells, and drugs. A quantification study is then performed to assure microsphere variation over various structures under imaging analysis. The obtained distribution characteristics are mimicked by the developed stochastic modeling study of microsphere distribution over 3D engineered freeform structures. Based on the stochastic approach, 3D porous structures are modeled and designed in CAD. Modeling of microsphere and encapsulating biomaterial distribution in this work helps develop comprehensive modeling of biomolecule release kinetics for further research. A novel multichamber single nozzle solid freeform fabrication technique is utilized to fabricate sample structures. The presented methods are implemented and illustrative examples are presented in this paper.


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