Solid Freeform Fabrication of Polycaprolactone∕Hydroxyapatite Tissue Scaffolds

Author(s):  
L. Shor ◽  
S. Güçeri ◽  
M. Gandhi ◽  
X. Wen ◽  
W. Sun

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.

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1319
Author(s):  
Muhammad Umar Aslam Khan ◽  
Wafa Shamsan Al-Arjan ◽  
Mona Saad Binkadem ◽  
Hassan Mehboob ◽  
Adnan Haider ◽  
...  

Bone tissue engineering is an advanced field for treatment of fractured bones to restore/regulate biological functions. Biopolymeric/bioceramic-based hybrid nanocomposite scaffolds are potential biomaterials for bone tissue because of biodegradable and biocompatible characteristics. We report synthesis of nanocomposite based on acrylic acid (AAc)/guar gum (GG), nano-hydroxyapatite (HAp NPs), titanium nanoparticles (TiO2 NPs), and optimum graphene oxide (GO) amount via free radical polymerization method. Porous scaffolds were fabricated through freeze-drying technique and coated with silver sulphadiazine. Different techniques were used to investigate functional group, crystal structural properties, morphology/elemental properties, porosity, and mechanical properties of fabricated scaffolds. Results show that increasing amount of TiO2 in combination with optimized GO has improved physicochemical and microstructural properties, mechanical properties (compressive strength (2.96 to 13.31 MPa) and Young’s modulus (39.56 to 300.81 MPa)), and porous properties (pore size (256.11 to 107.42 μm) and porosity (79.97 to 44.32%)). After 150 min, silver sulfadiazine release was found to be ~94.1%. In vitro assay of scaffolds also exhibited promising results against mouse pre-osteoblast (MC3T3-E1) cell lines. Hence, these fabricated scaffolds would be potential biomaterials for bone tissue engineering in biomedical engineering.


2019 ◽  
Vol 33 (8) ◽  
pp. 1128-1144 ◽  
Author(s):  
Vahideh Raeisdasteh Hokmabad ◽  
Soodabeh Davaran ◽  
Marziyeh Aghazadeh ◽  
Reza Rahbarghazi ◽  
Roya Salehi ◽  
...  

The major challenge of tissue regeneration is to develop three dimensional scaffolds with suitable properties which would mimic the natural extracellular matrix to induce the adhesion, proliferation, and differentiation of cells. Several materials have been used for the preparation of the scaffolds for bone regeneration. In this study, novel ethyl cellulose-grafted-poly (ɛ-caprolactone) (EC-g-PCL)/alginate scaffolds with different contents of nano-hydroxyapatite were prepared by combining electrospinning and freeze-drying methods in order to provide nanofibrous/macroporous structures with good mechanical properties. For this aim, EC-g-PCL nanofibers were obtained with electrospinning, embedded layer-by-layer in alginate solutions containing nano-hydroxyapatite particles, and finally, these constructions were freeze-dried. The scaffolds possess highly porous structures with interconnected pore network. The swelling, porosity, and degradation characteristics of the EC-g-PCL/alginate scaffolds were decreased with the increase in nano-hydroxyapatite contents, whereas increases in the in-vitro biomineralization and mechanical strength were observed as the nano-hydroxyapatite content was increased. The cell response to EC-g-PCL/alginate scaffolds with/or without nano-hydroxyapatite was investigated using human dental pulp stem cells (hDPSCs). hDPSCs displayed a high adhesion, proliferation, and differentiation on nano-hydroxyapatite-incorporated EC-g-PCL/alginate scaffolds compared to pristine EC-g-PCL/alginate scaffold. Overall, these results suggested that the EC-g-PCL/alginate-HA scaffolds might have potential applications in bone tissue engineering.


2013 ◽  
Vol 2 (4) ◽  
pp. 427-447 ◽  
Author(s):  
Bapi Sarker ◽  
Stefan Lyer ◽  
Andreas Arkudas ◽  
Aldo R. Boccaccini

AbstractCollagen is increasingly attracting attention for bone tissue engineering applications. However, due to its low mechanical properties, applications including mechanical loads or requiring structural integrity are limited. To tackle this handicap, collagen can be combined with (nanoscale) silica in a variety of composite materials that are attractive for bone tissue engineering. Considering research carried out in the past 15 years, this article reviews the literature discussing the development of silica/collagen composites that have been synthesized by adding silica from different sources as inorganic bioactive material to collagen as organic matrix. Different routes for the fabrication of collagen/silica composites are presented, focusing on nanocomposites. In vitro cell bioactivity studies demonstrated the osteogenic and, in some cases, angiogenic potential of the composites. Relevant in vivo studies discussing integration of the materials in bone tissue are discussed. Due to the understanding of possible interaction between silicon species and collagen, the effect of different silica precursors on the collagen self-assembly process is also discussed. On the basis of literature results and as discussed in this review, collagen/silica nanocomposites and hybrids represent attractive biomaterials for bone regeneration applications.


2020 ◽  
Author(s):  
weiling huo ◽  
Xiaodong Wu ◽  
Yancheng zheng ◽  
Jian Cheng ◽  
Qiang Xu ◽  
...  

Reconstruction of bone defect is one of the difficult problems in orthopedic treatment, and bone tissue scaffold implantation is the most promising direction of bone defect reconstruction. In this study, we used the combination of HA (Hydroxyapatite) and PLGA [Poly (lactic-co-glycolic acid)] in the construction of polymer scaffolds, and introduced bioactive MSM (Methyl sulfonyl methane) into polymer scaffolds to prepare porous scaffolds. The osteoblasts, isolated and cultured in vitro, were seeded in the porous scaffolds to construct tissue-engineered scaffolds. Meanwhile, the model of rabbit radius defect was constructed to evaluate the biological aspects of five tissue-engineered scaffolds, which provided experimental basis for the application of the porous scaffolds in bone tissue engineering. The SEM characterization showed the pore size of porous scaffolds was uniform and the porosity was about 90%. The results of contact Angle testing suggested that the hydrophobic porous scaffold surface could effectively promote cell adhesion and cell proliferation, while mechanical property test showed good machinability. The results of drug loading and release efficiency of MSM showed that porous scaffolds could load MSM efficiently and prolong the release time of MSM. In vitro incubation of porous scaffolds and osteoblasts showed that the addition of a small quantity of MSM could promote the infiltration and proliferation of osteoblasts on the porous scaffolds. Similar results were obtained by implanting the tissue-engineered scaffolds, fused with the osteoblasts and MSM/HA/PLGA porous scaffolds, into the rabbit radius defect, which provided experimental basis for the application of the MSM/HA/PLGA porous scaffolds in bone tissue engineering.


Author(s):  
Tran Thanh Hoai ◽  
Nguyen Kim Nga

In this study, porous scaffolds were fabricated using inorganic material-hydroxyapatite and chitosan for bone-tissue engineering. The combination of hydroxyapatite and chitosan may result in increasing biocompatibility of the scaffolds. The scaffolds were prepared by solvent casting and paticulate leaching method. Bioactivity of the scaffolds was evaluated through in vitro experiments by soaking scaffold samples in simulated body fluid (SBF). The scaffolds obtained were highly porous and interconnected with a mean pore size of around 200µm and porosity about 79 %. The apatite-mineral layer was produced on the HAp/chitosan after 10 days of soaking in SBF, however, it was not observed on the chitosan scaffold after 10 days soaking. The results revealed that the HAp/chitosan scaffold showed better bioactivity than the chitosan scaffold. Keywords Scaffold, Chitosan, Apatite, SBF. In this study, porous scaffolds were fabricated using inorganic material-hydroxyapatite and chitosan for bone-tissue engineering. The combination of hydroxyapatite and chitosan may result in increasing biocompatibility of the scaffolds. The scaffolds were prepared by solvent casting and paticulate leaching method. Bioactivity of the scaffolds was evaluated through in vitro experiments by soaking scaffold samples in simulated body fluid (SBF). The scaffolds obtained were highly porous and interconnected with a mean pore size of around 200µm and porosity about 79 %. The apatite-mineral layer was produced on the HAp/chitosan after 10 days of soaking in SBF, however, it was not observed on the chitosan scaffold after 10 days soaking. The results revealed that the HAp/chitosan scaffold showed better bioactivity than the chitosan scaffold. Keywords: Scaffold, Chitosan, Apatite, SBF.   In this study, porous scaffolds were fabricated using inorganic material-hydroxyapatite and chitosan for bone-tissue engineering. The combination of hydroxyapatite and chitosan may result in increasing biocompatibility of the scaffolds. The scaffolds were prepared by solvent casting and paticulate leaching method. Bioactivity of the scaffolds was evaluated through in vitro experiments by soaking scaffold samples in simulated body fluid (SBF). The scaffolds obtained were highly porous and interconnected with a mean pore size of around 200µm and porosity about 79 %. The apatite-mineral layer was produced on the HAp/chitosan after 10 days of soaking in SBF, however, it was not observed on the chitosan scaffold after 10 days soaking. The results revealed that the HAp/chitosan scaffold showed better bioactivity than the chitosan scaffold. Keywords: Scaffold, Chitosan, Apatite, SBF. References [1] M.P. Bostrom, D.A. Seigerman, The clinical use of allografts, demineralized bone matrices, synthetic bone graft substitutes and osteoinductive growth factors: a survey study, Hss. Journal 1 (2005) 9-18. https://doi.org/10. 1007/s11420-005-0111-5.[2] T.T. Hoai, N.K Nga, L.T. Giang, T.Q. Huy, P.N.M. Tuan, B.T.T. Binh, Hydrothermal Synthesis of Hydroxyapatite Nanorods for Rapid Formation of Bone-Like Mineralization, J. Electron. Mater. 46 (2017) 5064-5072. https:// doi.org/10.1007/s11664-017-5509-6.[3] M. Rinaudo, Chitin and chitosan: properties and applications, Prog. Polym. Sci. 31 (2006) 603-632. https://doi.org/10.1016/j.progpolymsci.2006. 06.001.[4] N.K. Nga, H.D. Chinh, P.T.T Hong, T.Q. Huy, Facile chitosan films for high performance removal of reactive blue 19 dye from aqueous solution, J. Polym. Environ. 25 (2007) 146-155. https://doi.org/10.1007/s10924-016-0792-5.[5] M.N.V Ravi Kumar, R.A.A Muzzarelli, H. Sashiwa, A.J. Domb, Chitosan chemistry and pharmaceutical perspectives, Chem. Rev. 104 (2004) 6017-6084. https://doi.org/10.1021/cr03 0441b.[6] J.M. Karp, M.S. Shoichet, J.E. Davies, Bone formation on two‐dimensional poly (DL‐lactide‐co‐glycolide)(PLGA) films and three‐dimensional PLGA tissue engineering scaffolds in vitro, J. Biomed. Mater. Res. A 64 (2003) 388-396. https://doi.org/10.1002/jbm.a.10420.[7] J.F. Mano, R.L. Reis, Osteochondral defects: present situation and tissue engineering approaches, J. Tissue. Eng. Regen. Med. 1 (2007) 261-273. https://doi.org/10.1002/term.37. [8] A.G. Mikos, J.S. Temenoff, Formation of highly porous biodegradable scaffolds for tissue engineering, Electron. J. Biotechn. 3 (2000) 23-24. http://dx.doi.org/10.4067/S0717-3458200000 0200003.[9] W.W. Thein-Han, R.D.K Misra, Biomimetic chitosan–nanohydroxyapatite composite scaffolds for bone tissue engineering, Acta Biomater. 5 (2009) 1182–1197. https://doi.org/ 10.1016/j.actbio.2008.11.025.[10] Y. Zhang, J.R. Venugopal, A.E. Turki, S. Ramakrishna, B. Su, C.T. Lim, Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for bone tissue engineering, Biomaterials 29 (2008) 4314–4322. https://doi.org/10.1016/j.biomaterials.2008.07.038.[11] B.X. Vương, Tổng hợp và đặc trưng vật liệu composite hydroxyapatite/chitosan ứng dụng trong kỹ thuật y sinh.,Tạp chí Khoa học ĐHQGHN: Khoa học Tự nhiên và Công nghệ Tập 34 (2018) 9-15. https://doi.org/10.25073/ 2588-1140/vnunst.4689.[12] N.K. Nga, T.T. Hoai, P.H. Viet, Biomimetic scaffolds based on hydroxyapatite nanorod/poly (D, L) lactic acid with their corresponding apatite-forming capability and biocompatibility for bone-tissue engineering, Colloids Surf. B Biointerf. 128 (2015) 506-514. https://doi.org/10. 1016/j.colsurfb.2015.03.001.[13] N.K. Nga, L.T. Giang, T.Q. Huy, C. Migliaresi, Surfactant-assisted size control of hydroxyapatite nanorods for bone tissue engineering, Colloids Surf. B: Biointerf. 116 (2014) 666-673. https://doi.org/10.1016/j.colsurfb.2013.11.001.[14] C.R. Kothapalli, M.T. Shaw, M. Wei, Biodegradable HA-PLA 3-D porous scaffolds: effect of nano-sized filler content on scaffold properties, Acta Biomater. 1 (2005) 653-662. https://doi.org/10.1016/j.actbio.2005.06.005.[15] T. Kokubo, H. Takadama, How useful is SBF in predicting in vivo bone bioactivity?, Biomaterials 27 (2006) 2907-2915. https://doi.org/10.1016/j. biomaterials.2006.01.017[16] T.T. Hoai, N.K. Nga, Effect of pore architecture on osteoblast adhesion and proliferation on hydroxyapatite/poly (D, L) lactic acid-based bone scaffolds, J. Iran. Chem. Soc. 15 (2018) 1663-1671. https://doi.org/10.1007/s13738-018-1365-4.        


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.


Coatings ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1120
Author(s):  
Wafa Shamsan Al-Arjan ◽  
Muhammad Umar Aslam Khan ◽  
Samina Nazir ◽  
Saiful Izwan Abd Razak ◽  
Mohammed Rafiq Abdul Kadir

Fabrication of reinforced scaffolds to repair and regenerate defected bone is still a major challenge. Bone tissue engineering is an advanced medical strategy to restore or regenerate damaged bone. The excellent biocompatibility and osteogenesis behavior of porous scaffolds play a critical role in bone regeneration. In current studies, we synthesized polymeric nanocomposite material through free-radical polymerization to fabricate porous nanocomposite scaffolds by freeze drying. Functional group, surface morphology, porosity, pore size, and mechanical strength were examined through Fourier Transform Infrared Spectroscopy (FTIR), Single-Electron Microscopy (SEM), Brunauer-Emmet-Teller (BET), and Universal Testing Machine (UTM), respectively. These nanocomposites exhibit enhanced compressive strength (from 4.1 to 16.90 MPa), Young’s modulus (from 13.27 to 29.65 MPa) with well appropriate porosity and pore size (from 63.72 ± 1.9 to 45.75 ± 6.7 µm), and a foam-like morphology. The increasing amount of graphene oxide (GO) regulates the porosity and mechanical behavior of the nanocomposite scaffolds. The loading and sustained release of silver-sulfadiazine was observed to be 90.6% after 260 min. The in-vitro analysis was performed using mouse pre-osteoblast (MC3T3-E1) cell lines. The developed nanocomposite scaffolds exhibited excellent biocompatibility. Based on the results, we propose these novel nanocomposites can serve as potential future biomaterials to repair defected bone with the load-bearing application, and in bone tissue engineering.


2021 ◽  
Author(s):  
Chengyong Li ◽  
Tingting Yan ◽  
Zhenkai Lou ◽  
Zhimin Jiang ◽  
Zhi Shi ◽  
...  

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.


2011 ◽  
Vol 26 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Taís Somacal Novaes Silva ◽  
Bruno Tochetto Primo ◽  
Aurelício Novaes Silva Júnior ◽  
Denise Cantarelli Machado ◽  
Christian Viezzer ◽  
...  

Purpose: To evaluate the ability of macroporous tricalcium phosphate cement (CPC) scaffolds to enable the adhesion, proliferation, and differentiation of mesenchymal stem cells derived from human bone marrow. Methods: Cells from the iliac crest of an adult human donor were processed and cultured on macroporous CPC discs. Paraffin spheres sized between 100 and 250µm were used as porogens. Cells were cultured for 5, 10, and 15 days. Next, we assessed cells' behavior and morphology on the biomaterial by scanning electron microscopy. The expression levels of the BGLA and SSP1 genes and the alkaline phosphatase (ALP) activity were quantified by the quantitative real-time polymerase chain reaction technique (QT-PCR) using the fluorophore SYBR GREEN®. Results: QT-PCR detected the expression of the BGLA and SSP1 genes and the ALP activity in the periods of 10 and 15 days of culture. Thus, we found out that there was cell proliferation and differentiation in osteogenic cells. Conclusion: Macroporous CPC, with pore sized between 100 and 250µm and developed using paraffin spheres, enables adhesion, proliferation, and differentiation of mesenchymal stem cells in osteogenic cells and can be used as a scaffold for bone tissue engineering.


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