Development of HA-PLGA Scaffold Encapsulating Intact BMP-2 Using Solid Freeform Fabrication Technology

2011 ◽  
Author(s):  
Jin-Hyung Shim ◽  
Jong Young Kim ◽  
Kyung Shin Kang ◽  
Jung Kyu Park ◽  
Sei Kwang Hahn ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Porous Scaffold ◽  
Solid Freeform Fabrication ◽  
Three Dimensional ◽  
Porous Scaffolds ◽  
Prolonged Release ◽  
Cellular Activity ◽  
Freeform Fabrication

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.

Solid Freeform Fabrication of Polycaprolactone∕Hydroxyapatite Tissue Scaffolds

2008 ◽  
Vol 130 (2) ◽  
Author(s):  
L. Shor ◽  
S. Güçeri ◽  
M. Gandhi ◽  
X. Wen ◽  
W. Sun
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Structural Integrity ◽  
Solid Freeform Fabrication ◽  
Porous Scaffolds ◽  
Freeform Fabrication ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

Bone tissue engineering is an emerging field providing viable substitutes for bone regeneration. Freeform fabrication provides an effective process tool to manufacture scaffolds with complex shapes and designed properties. We developed a novel precision extruding deposition (PED) technique to fabricate composite polycaprolactone∕hydroxyapatite (PCL∕HA) scaffolds. 25% concentration by weight of HA was used to reinforce 3D scaffolds. Two groups of scaffolds having 60% and 70% porosities and with pore sizes of 450μm and 750μm respectively, were evaluated for their morphology and compressive properties using scanning electron microscopy and the mechanical testing. In vitro cell-scaffold interaction study was carried out using primary fetal bovine osteoblasts. The cell proliferation and differentiation were evaluated by Alamar Blue assay and alkaline phosphatase activity. Our results suggested that compressive modulus of PCL∕HA scaffold was 84MPa for 60% porous scaffolds and was 76MPa for 70% porous scaffolds. The osteoblasts were able to migrate and proliferate for the cultured time over the scaffolds. Our study demonstrated the viability of the PED process to fabricate PCL scaffolds having necessary mechanical property, structural integrity, controlled pore size, and pore interconnectivity desired for bone tissue engineering.

scholarly journals Porous Geometry Guided Micro-mechanical Environment Within Scaffolds for Cell Mechanobiology Study in Bone Tissue Engineering

2021 ◽  
Vol 9 ◽  
Author(s):  
Feihu Zhao ◽  
Yi Xiong ◽  
Keita Ito ◽  
Bert van Rietbergen ◽  
Sandra Hofmann
Keyword(s):  
Porous Scaffold ◽  
Mechanical Strain ◽  
Three Dimensional ◽  
Pore Geometry ◽  
Cell Physiology ◽  
Porous Scaffolds ◽  
Mechanical Environment ◽  
Functional Features ◽  
Future Work

Mechanobiology research is for understanding the role of mechanics in cell physiology and pathology. It will have implications for studying bone physiology and pathology and to guide the strategy for regenerating both the structural and functional features of bone. Mechanobiological studies in vitro apply a dynamic micro-mechanical environment to cells via bioreactors. Porous scaffolds are commonly used for housing the cells in a three-dimensional (3D) culturing environment. Such scaffolds usually have different pore geometries (e.g. with different pore shapes, pore dimensions and porosities). These pore geometries can affect the internal micro-mechanical environment that the cells experience when loaded in the bioreactor. Therefore, to adjust the applied micro-mechanical environment on cells, researchers can tune either the applied load and/or the design of the scaffold pore geometries. This review will provide information on how the micro-mechanical environment (e.g. fluid-induced wall shear stress and mechanical strain) is affected by various scaffold pore geometries within different bioreactors. It shall allow researchers to estimate/quantify the micro-mechanical environment according to the already known pore geometry information, or to find a suitable pore geometry according to the desirable micro-mechanical environment to be applied. Finally, as future work, artificial intelligent – assisted techniques, which can achieve an automatic design of solid porous scaffold geometry for tuning/optimising the micro-mechanical environment are suggested.

Mineralized Nanofibers for Bone Tissue Engineering

2018 ◽  
pp. 461-475 ◽  
Author(s):  
Ozan Karaman
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Three Dimensional ◽  
Bone Grafts ◽  
Tissue Engineering Scaffolds ◽  
Promising Alternative ◽  
Biomimetic Scaffolds

The limitation of orthopedic fractures and large bone defects treatments has brought the focus on fabricating bone grafts that could enhance ostegenesis and vascularization in-vitro. Developing biomimetic materials such as mineralized nanofibers that can provide three-dimensional templates of the natural bone extracellular-matrix is one of the most promising alternative for bone regeneration. Understanding the interactions between the structure of the scaffolds and cells and therefore the control cellular pathways are critical for developing functional bone grafts. In order to enhance bone regeneration, the engineered scaffold needs to mimic the characteristics of composite bone ECM. This chapter reviews the fabrication of and fabrication techniques for fabricating biomimetic bone tissue engineering scaffolds. In addition, the chapter covers design criteria for developing the scaffolds and examples of enhanced osteogenic differentiation outcomes by fabricating biomimetic scaffolds.

Preparation and Characterization of Ha/Gel/β-TCP Microspheres Composite Porous Scaffold

2018 ◽  
Vol 782 ◽  
pp. 103-115
Author(s):  
Yang Zi Zhao ◽  
You Fa Wang
Keyword(s):  
Tissue Engineering ◽  
Compressive Strength ◽  
Hyaluronic Acid ◽  
Pore Size ◽  
Porous Scaffold ◽  
Three Dimensional ◽  
Swelling Ratio ◽  
Cell Compatibility ◽  
Hydrogel Scaffolds

Being one of the three elements of tissue engineering, three-dimensional porous structure scaffold plays an important role in tissue engineering. As it not only prvovide cells for the life, but also serves as a template to guide tissue regeneration and control of organizational structure and other functions. In this study, hyaluronic acid and gelatin are successfully cross-linked by 1-ethyl- (3-dimethylaminopropyl) -carbodiimide hydrochloride (EDC) , and compound β-TCP microspheres to prepare porous hydrogel scaffolds. The microspheres were analyzed by X-ray diffraction (XRD). The scaffolds were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). At the same time, the compressive strength, swelling ratio, degradation of the scaffold were tested. To assess the in vitro cell compatibility of the scaffolds, mouse L929 fibroblasts were seeded onto scaffolds for cell morphology and cell viability studies. The results showed that the pore size of the porous scaffold can be adjusted by changing the ratio of gelatin to hyaluronic acid (HA), increasing the proportion of hyaluronic acid in a certain range, pore size will be significantly increased. With the increase of the proportion of hyaluronic acid in the scaffold, the swelling ratio and the degradation rate also increased. The compressive strength of the scaffold increased with the increase of the proportion of gelatin. The appropriate ratio of β-TCP can promote cell growth and proliferation.

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

2005 ◽  
Author(s):  
Daniel L. Cohen ◽  
Evan Malone ◽  
Hod Lipson ◽  
Lawrence J. Bonassar
Keyword(s):  
Tissue Engineering ◽  
Solid Freeform Fabrication ◽  
Crosslinking Agent ◽  
Three Dimensional ◽  
Patient Specific ◽  
Efficient Production ◽  
Alginate Hydrogel ◽  
Freeform Fabrication ◽  
Patient Specific Implants ◽  
Multiple Material

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.

scholarly journals Geometric Modeling of Cellular Materials for Additive Manufacturing in Biomedical Field: A Review

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Gianpaolo Savio ◽  
Stefano Rosso ◽  
Roberto Meneghello ◽  
Gianmaria Concheri
Keyword(s):  
Tissue Engineering ◽  
Additive Manufacturing ◽  
Geometric Modeling ◽  
Solid Freeform Fabrication ◽  
Cellular Materials ◽  
Point Of View ◽  
Porous Scaffolds ◽  
Freeform Fabrication ◽  
Geometric Point ◽  
Manufacturing Technologies

Advances in additive manufacturing technologies facilitate the fabrication of cellular materials that have tailored functional characteristics. The application of solid freeform fabrication techniques is especially exploited in designing scaffolds for tissue engineering. In this review, firstly, a classification of cellular materials from a geometric point of view is proposed; then, the main approaches on geometric modeling of cellular materials are discussed. Finally, an investigation on porous scaffolds fabricated by additive manufacturing technologies is pointed out. Perspectives in geometric modeling of scaffolds for tissue engineering are also proposed.

scholarly journals Graphene Coated Scaffold for Bone Tissue Engineering: Physicochemical and Osteogenic Characterizations

2021 ◽  
Author(s):  
Sajad Bahrami ◽  
Nafiseh Baheiraei ◽  
Mostafa Shahrezaee
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue ◽  
Three Dimensional ◽  
Chemical Properties ◽  
Cranial Bone ◽  
Drying Methods ◽  
Porous Scaffolds ◽  
Alizarin Red

Abstract Variety of bone-related diseases and injures and limitations of traditional regeneration methods need to introduce new tissue substitutes. Tissue engineering and regeneration combined with nanomedicine can provide different natural or synthetic and combined scaffolds with bone mimicking properties for implant in the injured area. In this study, we synthesized collagen (Col) and reduced graphene oxide coated collagen (Col-rGO) scaffolds and evaluated their in vitro and in vivo effects on bone tissue repair. Col and Col-rGO scaffolds were synthesized by chemical crosslinking and freeze-drying methods. The surface topography, mechanical and chemical properties of scaffolds were characterized and showed three-dimensional (3D) porous scaffolds and successful coating of rGO on Col. rGO coating enhanced mechanical strength of Col-rGO scaffolds compared with Col scaffolds by 2.8 folds. Furthermore, Col-rGO scaffolds confirmed that graphene addition not only did not any cytotoxic effects but also enhanced human bone marrow-derived mesenchymal stem cells (hBMSCs) viability and proliferation with 3D adherence and expansion. Finally, scaffolds implantation into rabbit cranial bone defect for 12 weeks showed increased bone formation, confirmed by Hematoxylin-Eosin (H&E) and alizarin red staining. Altogether, the study showed that rGO coating improves Col scaffold properties and could be a promising implant for bone injuries.

scholarly journals Characterization and In Vitro Assessment Of Three-Dimensional Extrusion Mg-Sr Codoped SiO2-Complexed Porous Micro-Hydroxyapatite Whisker Scaffolds For Bone Tissue Engineering

2021 ◽  
Author(s):  
Chengyong Li ◽  
Tingting Yan ◽  
Zhenkai Lou ◽  
Zhimin Jiang ◽  
Zhi Shi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Bone Repair ◽  
Three Dimensional ◽  
Chemical Properties ◽  
Treatment Method ◽  
Porous Scaffolds ◽  
Active Elements

Abstract Background Orthopedics has made great progress with the development of medical treatment; however, large bone defects are still great challenges for orthopedic surgeons. A good bone substitute that can be obtained through bone tissue engineering may be an effective treatment method. Artificial hydroxyapatite is the main inorganic component of bones, but its applications are limited due to its fragility and lack of bone-active elements. Therefore, it is necessary to reduce its fragility and improve its biological activity. Methods In this study, we developed micro-hydroxyapatite whiskers (mHAws), which were doped with the essential trace active elements Mg2+ and Sr2+ through a low-temperature sintering technique, used silica complexes to improve the mechanical properties, and then manufactured the bionic porous scaffolds by extrusion molding and freeze-drying. Results Four types of scaffolds were obtained: mHAw-SiO2, Mg-doped mHAw-SiO2, Sr-doped mHAw-SiO2 and Mg-Sr-codoped mHAw-SiO2. These composite porous scaffolds have been suggested to have a sufficiently porous morphology with appropriate mechanical strength, are noncytotoxic, are able to support cell proliferation and spreading, and, more importantly, can promote the osteogenic differentiation of rBMSCs. Conclusion Therefore, these doped scaffolds not only have physical and chemical properties suitable for bone tissue engineering, but also have higher osteogenic bioactivity, and can be possibly serve as potential bone repair material.

Mineralized Nanofibers for Bone Tissue Engineering

2017 ◽  
pp. 200-218
Author(s):  
Ozan Karaman
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Three Dimensional ◽  
Bone Grafts ◽  
Tissue Engineering Scaffolds ◽  
Promising Alternative ◽  
Biomimetic Scaffolds

The limitation of orthopedic fractures and large bone defects treatments has brought the focus on fabricating bone grafts that could enhance ostegenesis and vascularization in-vitro. Developing biomimetic materials such as mineralized nanofibers that can provide three-dimensional templates of the natural bone extracellular-matrix is one of the most promising alternative for bone regeneration. Understanding the interactions between the structure of the scaffolds and cells and therefore the control cellular pathways are critical for developing functional bone grafts. In order to enhance bone regeneration, the engineered scaffold needs to mimic the characteristics of composite bone ECM. This chapter reviews the fabrication of and fabrication techniques for fabricating biomimetic bone tissue engineering scaffolds. In addition, the chapter covers design criteria for developing the scaffolds and examples of enhanced osteogenic differentiation outcomes by fabricating biomimetic scaffolds.

scholarly journals Development and in vitro evaluation of κ-carrageenan based polymeric hybrid nanocomposite scaffolds for bone tissue engineering

RSC Advances ◽  
2020 ◽  
Vol 10 (66) ◽  
pp. 40529-40542 ◽  
Author(s):  
Muhammad Umar Aslam Khan ◽  
Mohsin Ali Raza ◽  
Hassan Mehboob ◽  
Mohammed Rafiq Abdul Kadir ◽  
Saiful Izwan Abd Razak ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Vital Role ◽  
Porous Scaffolds ◽  
Hybrid Nanocomposite ◽  
In Vitro Evaluation ◽  
Nanocomposite Scaffolds

The excellent biocompatible and osteogenesis characteristics of porous scaffolds play a vital role in bone regeneration.

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