scholarly journals Customized Ca–P/PHBV nanocomposite scaffolds for bone tissue engineering: design, fabrication, surface modification and sustained release of growth factor

2010 ◽  
Vol 7 (suppl_5) ◽  
Author(s):  
Bin Duan ◽  
Min Wang

Integrating an advanced manufacturing technique, nanocomposite material and controlled delivery of growth factor to form multifunctional tissue engineering scaffolds was investigated in this study. Based on calcium phosphate (Ca–P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanocomposite microspheres, three-dimensional Ca–P/PHBV nanocomposite scaffolds with customized architecture, controlled porosity and totally interconnected porous structure were successfully fabricated using selective laser sintering (SLS), one of the rapid prototyping technologies. The cytocompatibility of sintered Ca–P/PHBV nanocomposite scaffolds, as well as PHBV polymer scaffolds, was studied. For surface modification of nanocomposite scaffolds, gelatin was firstly physically entrapped onto the scaffold surface and heparin was subsequently immobilized on entrapped gelatin. The surface-modification improved the wettability of scaffolds and provided specific binding site between conjugated heparin and the growth factor recombinant human bone morphogenetic protein-2 (rhBMP-2). The surface-modified Ca–P/PHBV nanocomposite scaffolds loaded with rhBMP-2 significantly enhanced the alkaline phosphatase activity and osteogenic differentiation markers in gene expression of C3H10T1/2 mesenchymal stem cells. Together with osteoconductive nanocomposite material and controlled growth factor delivery strategies, the use of SLS technique to form complex scaffolds will provide a promising route towards individualized bone tissue regeneration.

2011 ◽  
Vol 1301 ◽  
Author(s):  
Min Wang ◽  
Bin Duan

ABSTRACTFrom the material point of view, the extracellular matrix (ECM) of bone is a natural nanocomposite consisting of an organic matrix (mainly collagen) and inorganic nanofillers (bone apatite) which are inserted in a parallel way into the collagen fibrils. For human bone tissue repair or regeneration, nanocomposites consisting of a biodegradable polymer matrix and nano-sized fillers such as bioactive ceramics or glasses, which mimic the hierarchical structure of bone, are considered a promising strategy. Combining living cells with biodegradable materials and/or bioactive component(s), the concept of tissue engineering first elucidated in the early 1990s represented a paradigm shift from tissue grafting, with autografts being the gold standard, or even completely from prosthesis implantation. In scaffold-based tissue engineering, scaffolds play an important role for tissue regeneration. Currently, acellular scaffolds with or without biomolecules such as growth factors are considered as an effective strategy for certain tissue repair due to their relatively low costs and easier process to gain surgeons’ acceptance and regulatory approval. In the current study, integrating an advanced manufacturing technique, nanocomposite material and controlled delivery of growth factor to form multifunctional tissue engineering scaffolds was investigated. Three-dimensional, osteoconductive and totally biodegradable calcium phosphate (Ca-P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanocomposite scaffolds with customized architecture, controlled porosity and interconnecting pores were designed and fabricated using selective laser sintering (SLS). The surface of nanocomposite scaffolds was modified with gelatin and then heparin, which facilitated the incorporation of a growth factor, recombinant human bone morphogenetic protein-2 (rhBMP-2). Experimental results demonstrated the effectiveness of this strategy in guiding the osteogenic differentiation of mesenchymal stem cells. Together with osteoconductive nanocomposite material and controlled growth factor delivery, the use of SLS technique to form complex scaffolds provides a promising route towards individualized bone tissue regeneration.


Nano LIFE ◽  
2012 ◽  
Vol 02 (01) ◽  
pp. 1250005 ◽  
Author(s):  
BIN DUAN ◽  
MIN WANG ◽  
WILLIAM W. LU

Selective laser sintering (SLS), a rapid prototyping technology, was investigated for producing bone tissue engineering scaffolds. Completely biodegradable osteoconductive calcium phosphate (Ca-P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) scaffolds were successfully fabricated via SLS using Ca-P/PHBV nanocomposite microspheres. In the SLS manufacturing route, the architecture of tissue engineering scaffolds (pore shape, size, interconnectivity, etc.) can be designed and the sintering process can be optimized for obtaining scaffolds with desirable porous structures and mechanical properties. SLS was also shown to be very effective in producing highly complex porous structures using nanocomposite microspheres. To render SLS-formed Ca-P/PHBV scaffolds osteoinductive, recombinant human bone morphogenetic protein-2 (rhBMP-2) could be loaded onto the scaffolds. For achieving a controlled release of rhBMP-2 from scaffolds, surface modification of Ca-P/PHBV scaffolds by gelatin entrapment and heparin immobilization was needed. The immobilized heparin provided binding affinity for rhBMP-2. Surface modified Ca-P/PHBV nanocomposite scaffolds loaded with rhBMP-2 enhanced the proliferation of human umbilical cord derived mesenchymal stem cells (hUCMSCs) and also their alkaline phosphatase activity. In in vivo experiments using a rabbit model, surface modified Ca-P/PHBV nanocomposite scaffolds loaded with rhBMP-2 promoted ectopic bone formation, exhibiting their osteoinductivity. The strategy of combining advanced scaffold fabrication, nanocomposite material, and controlled growth factor delivery is promising for bone tissue regeneration.


Nanomedicine ◽  
2020 ◽  
Vol 15 (20) ◽  
pp. 1995-2017
Author(s):  
Guo Ye ◽  
Fangyuan Bao ◽  
Xianzhu Zhang ◽  
Zhe Song ◽  
Youguo Liao ◽  
...  

The global incidence of bone tissue injuries has been increasing rapidly in recent years, making it imperative to develop suitable bone grafts for facilitating bone tissue regeneration. It has been demonstrated that nanomaterials/nanocomposites scaffolds can more effectively promote new bone tissue formation compared with micromaterials. This may be attributed to their nanoscaled structural and topological features that better mimic the physiological characteristics of natural bone tissue. In this review, we examined the current applications of various nanomaterial/nanocomposite scaffolds and different topological structures for bone tissue engineering, as well as the underlying mechanisms of regeneration. The potential risks and toxicity of nanomaterials will also be critically discussed. Finally, some considerations for the clinical applications of nanomaterials/nanocomposites scaffolds for bone tissue engineering are mentioned.


2019 ◽  
Vol 62 (1) ◽  
Author(s):  
Yuqian Hu ◽  
Linlin Zheng ◽  
Jinhui Zhang ◽  
Lijuan Lin ◽  
Yue Shen ◽  
...  

Abstract Background In bone tissue engineering, the fabrication and biocompatibility of scaffold are crucial. Among many scaffold materials, nanohydroxyapatite (nHAP) and collagen (COL) are chosen as building materials of scaffold. At the same time, growth factors were also used to modify the scaffolds. Methods In this study, blending and freeze drying methods were adopted together in order to build basic fibroblast growth factor (bFGF)-bone morphogenetic protein-2 (BMP-2)-nHAP/COL scaffolds. ELISA was applied to test the release of bFGF and BMP-2 on the scaffold. The flow cytometry was used to identify bone marrow mesenchymal stem cells (BMSCs). Scanning electron microscope was adopted to observe scaffolds and cells morphology. BMSCs were seeded on the scaffolds to test the biological compatibility in vitro. Cells were counted to detect early cell adhesion. Cell counting kit-8 assay was adopted to detect cell proliferation and alkalinephosphatase assay was applied to detect cell activity. Results The characterization of bFGF-BMP-2-nHAP/COL scaffolds meets the requirements of ideal bone tissue engineering scaffolds. BMSCs that were isolated, purified and passaged satisfied the needs of further experiments. The growth status of cells on bFGF-BMP-2-nHAP/COL scaffolds was satisfactory. Cell adhesion was the highest in the bFGF-BMP-2-nHAP/COL scaffolds group. The cell viability and ALP activity of bFGF-BMP-2-nHAP/COL scaffolds group were the highest. Conclusion Taken together, bFGF-BMP-2-nHAP/COL scaffolds have good biocompatibility in vitro and promote adhesion, proliferation, differentiation of BMSCs.


Author(s):  
Xiaoyan Qin ◽  
Yixin Wu ◽  
Shuang Liu ◽  
Lei Yang ◽  
Hongxia Yuan ◽  
...  

Polycaprolactone (PCL) has been widely used as a scaffold material for tissue engineering. Reliable applications of the PCL scaffolds require overcoming their native hydrophobicity and obtaining the sustained release of signaling factors to modulate cell growth and differentiation. Here, we report a surface modification strategy for electrospun PCL nanofibers using an azide-terminated amphiphilic graft polymer. With multiple alkylation and pegylation on the side chains of poly-L-lysine, stable coating of the graft polymer on the PCL nanofibers was achieved in one step. Using the azide-alkyne “click chemistry”, we functionalized the azide-pegylated PCL nanofibers with dibenzocyclooctyne-modified nanocapsules containing growth factor, which rendered the nanofiber scaffold with satisfied cell adhesion and growth property. Moreover, by specific immobilization of pH-responsive nanocapsules containing bone morphogenetic protein 2 (BMP-2), controlled release of active BMP-2 from the PCL nanofibers was achieved within 21 days. When bone mesenchyme stem cells were cultured on this nanofiber scaffold, enhanced ossification was observed in correlation with the time-dependent release of BMP-2. The established surface modification can be extended as a generic approach to hydrophobic nanomaterials for longtime sustainable release of multiplex signaling proteins for tissue engineering.


2021 ◽  
Vol 8 (8) ◽  
pp. 107
Author(s):  
Lilis Iskandar ◽  
Lucy DiSilvio ◽  
Jonathan Acheson ◽  
Sanjukta Deb

Despite considerable advances in biomaterials-based bone tissue engineering technologies, autografts remain the gold standard for rehabilitating critical-sized bone defects in the oral and maxillofacial (OMF) region. A majority of advanced synthetic bone substitutes (SBS’s) have not transcended the pre-clinical stage due to inferior clinical performance and translational barriers, which include low scalability, high cost, regulatory restrictions, limited advanced facilities and human resources. The aim of this study is to develop clinically viable alternatives to address the challenges of bone tissue regeneration in the OMF region by developing ‘dual network composites’ (DNC’s) of calcium metaphosphate (CMP)—poly(vinyl alcohol) (PVA)/alginate with osteogenic ions: calcium, zinc and strontium. To fabricate DNC’s, single network composites of PVA/CMP with 10% (w/v) gelatine particles as porogen were developed using two freeze–thawing cycles and subsequently interpenetrated by guluronate-dominant sodium alginate and chelated with calcium, zinc or strontium ions. Physicochemical, compressive, water uptake, thermal, morphological and in vitro biological properties of DNC’s were characterised. The results demonstrated elastic 3D porous scaffolds resembling a ‘spongy bone’ with fluid absorbing capacity, easily sculptable to fit anatomically complex bone defects, biocompatible and osteoconductive in vitro, thus yielding potentially clinically viable for SBS alternatives in OMF surgery.


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.


Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 647
Author(s):  
Mohamed Saiful Firdaus Hussin ◽  
Aludin Mohd Serah ◽  
Khairul Azri Azlan ◽  
Hasan Zuhudi Abdullah ◽  
Maizlinda Izwana Idris ◽  
...  

Collecting information from previous investigations and expressing it in a scientometrics study can be a priceless guide to getting a complete overview of a specific research area. The aim of this study is to explore the interrelated connection between alginate, gelatine, and hydroxyapatite within the scope of bone tissue and scaffold. A review of traditional literature with data mining procedures using bibliometric analyses was considered to identify the evolution of the selected research area between 2009 and 2019. Bibliometric methods and knowledge visualization technologies were implemented to investigate diverse publications based on the following indicators: year of publication, document type, language, country, institution, author, journal, keyword, and number of citations. An analysis using a bibliometric study found that 7446 papers were located with the keywords “bone tissue” and “scaffold”, and 1767 (alginate), 185 (gelatine), 5658 (hydroxyapatite) papers with those specific sub keywords. The number of publications that relate to “tissue engineering” and bone more than doubled between 2009 (1352) and 2019 (2839). China, the United States and India are the most productive countries, while Sichuan University and the Chinese Academy of Science from China are the most important institutions related to bone tissue scaffold. Materials Science and Engineering C is the most productive journal, followed by the Journal of Biomedical Materials Research Part A. This paper is a starting point, providing the first bibliometric analysis study of bone tissue and scaffold considering alginate, gelatine and hydroxyapatite. A bibliometric analysis would greatly assist in giving a scientific insight to support desired future research work, not only associated with bone tissue engineering applications. It is expected that the analysis of alginate, gelatine and hydroxyapatite in terms of 3D bioprinting, clinical outcomes, scaffold architecture, and the regenerative medicine approach will enhance the research into bone tissue engineering in the near future. Continued studies into these research fields are highly recommended.


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