Nanocomposite Scaffolds for Bone Tissue Engineering: Design, Fabrication, Surface Modification and Sustained Release of Growth Factor

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.

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

Journal of The Royal Society Interface ◽

10.1098/rsif.2010.0127.focus ◽

2010 ◽

Vol 7 (suppl_5) ◽

Cited By ~ 91

Author(s):

Bin Duan ◽

Min Wang

Keyword(s):

Tissue Engineering ◽

Surface Modification ◽

Growth Factor ◽

Bone Tissue ◽

Specific Binding ◽

Nanocomposite Material ◽

Bone Morphogenetic Protein 2 ◽

Bone Tissue Regeneration ◽

Form Complex ◽

Nanocomposite Scaffolds

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.

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THREE-DIMENSIONAL NANOCOMPOSITE SCAFFOLDS FOR BONE TISSUE ENGINEERING: FROM DESIGN TO APPLICATION

Nano LIFE ◽

10.1142/s1793984411000396 ◽

2012 ◽

Vol 02 (01) ◽

pp. 1250005 ◽

Cited By ~ 1

Author(s):

BIN DUAN ◽

MIN WANG ◽

WILLIAM W. LU

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Rabbit Model ◽

Bone Morphogenetic Protein 2 ◽

Human Umbilical Cord ◽

Porous Structures ◽

Tissue Engineering Scaffolds ◽

Surface Modified ◽

Nanocomposite Scaffolds

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.

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Central Growth Factor Loaded Depots in Bone Tissue Engineering Scaffolds for Enhanced Cell Attraction

Tissue Engineering Part A ◽

10.1089/ten.tea.2016.0483 ◽

2017 ◽

Vol 23 (15-16) ◽

pp. 762-772 ◽

Cited By ~ 4

Author(s):

Mandy Quade ◽

Sven Knaack ◽

Ashwini Rahul Akkineni ◽

Anastasia Gabrielyan ◽

Anja Lode ◽

...

Keyword(s):

Tissue Engineering ◽

Growth Factor ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Tissue Engineering Scaffolds

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Controlled Multiple Growth Factor Delivery from Bone Tissue Engineering Scaffolds via Designed Affinity

Tissue Engineering Part A ◽

10.1089/ten.tea.2013.0358 ◽

2014 ◽

Vol 20 (15-16) ◽

pp. 2077-2087 ◽

Cited By ~ 38

Author(s):

Darilis Suárez-González ◽

Jae Sung Lee ◽

Alisha Diggs ◽

Yan Lu ◽

Brett Nemke ◽

...

Keyword(s):

Tissue Engineering ◽

Growth Factor ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Growth Factor Delivery ◽

Tissue Engineering Scaffolds

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HYDROXYAPATITE, ALGINATE, AND CHITOSAN FOR BONE SCAFFOLDS: SPECTROSCOPY STUDY

Dentika Dental Journal ◽

10.32734/dentika.v19i2.457 ◽

2016 ◽

Vol 19 (2) ◽

pp. 93-100

Author(s):

Lalita El Milla

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Functional Groups ◽

Bone Growth ◽

Three Dimensional ◽

Dimensional Structure ◽

Tissue Engineering Scaffolds ◽

Hydroxyapatite Powder ◽

Materials Used

Scaffolds is three dimensional structure that serves as a framework for bone growth. Natural materials are often used in synthesis of bone tissue engineering scaffolds with respect to compliance with the content of the human body. Among the materials used to make scafffold was hydroxyapatite, alginate and chitosan. Hydroxyapatite powder obtained by mixing phosphoric acid and calcium hydroxide, alginate powders extracted from brown algae and chitosan powder acetylated from crab. The purpose of this study was to examine the functional groups of hydroxyapatite, alginate and chitosan. The method used in this study was laboratory experimental using Fourier Transform Infrared (FTIR) spectroscopy for hydroxyapatite, alginate and chitosan powders. The results indicated the presence of functional groups PO43-, O-H and CO32- in hydroxyapatite. In alginate there were O-H, C=O, COOH and C-O-C functional groups, whereas in chitosan there were O-H, N-H, C=O, C-N, and C-O-C. It was concluded that the third material containing functional groups as found in humans that correspond to the scaffolds material in bone tissue engineering.

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Development of Biopolymeric Hybrid Scaffold-Based on AAc/GO/nHAp/TiO2 Nanocomposite for Bone Tissue Engineering: In-Vitro Analysis

Nanomaterials ◽

10.3390/nano11051319 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1319

Author(s):

Muhammad Umar Aslam Khan ◽

Wafa Shamsan Al-Arjan ◽

Mona Saad Binkadem ◽

Hassan Mehboob ◽

Adnan Haider ◽

...

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Guar Gum ◽

Porous Scaffolds ◽

Vitro Assay ◽

Vitro Analysis ◽

Nanocomposite Scaffolds

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.

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Therapeutic Effects of the Addition of Fibroblast Growth Factor-2 to Biodegradable Gelatin/Magnesium-Doped Calcium Silicate Hybrid 3D-Printed Scaffold with Enhanced Osteogenic Capabilities for Critical Bone Defect Restoration

Biomedicines ◽

10.3390/biomedicines9070712 ◽

2021 ◽

Vol 9 (7) ◽

pp. 712

Author(s):

Wei-Yun Lai ◽

Yen-Jen Chen ◽

Alvin Kai-Xing Lee ◽

Yen-Hong Lin ◽

Yu-Wei Liu ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Bone Tissue ◽

Tissue Regeneration ◽

Calcium Silicate ◽

Clinical Applications ◽

Fibroblast Growth Factor 2 ◽

Therapeutic Effects ◽

Fibroblast Growth ◽

3D Printed

Worldwide, the number of bone fractures due to traumatic and accidental injuries is increasing exponentially. In fact, repairing critical large bone defects remains challenging due to a high risk of delayed union or even nonunion. Among the many bioceramics available for clinical use, calcium silicate-based (CS) bioceramics have gained popularity due to their good bioactivity and ability to stimulate cell behavior. In order to improve the shortcomings of 3D-printed ceramic scaffolds, which do not easily carry growth factors and do not provide good tissue regeneration effects, the aim of this study was to use a gelatin-coated 3D-printed magnesium-doped calcium silicate (MgCS) scaffold with genipin cross-linking for regulating degradation, improving mechanical properties, and enhancing osteogenesis behavior. In addition, we consider the effects of fibroblast growth factor-2 (FGF-2) loaded into an MgCS scaffold with and without gelatin coating. Furthermore, we cultured the human Wharton jelly-derived mesenchymal stem cells (WJMSC) on the scaffolds and observed the biocompatibility, alkaline phosphatase activity, and osteogenic-related markers. Finally, the in vivo performance was assessed using micro-CT and histological data that revealed that the hybrid bioscaffolds were able to further achieve more effective bone tissue regeneration than has been the case in the past. The above results demonstrated that this type of processing had great potential for future clinical applications and studies and can be used as a potential alternative for future bone tissue engineering research, as well as having good potential for clinical applications.

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Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis

Journal of Nanobiotechnology ◽

10.1186/s12951-020-00755-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Hamed Nosrati ◽

Reza Aramideh Khouy ◽

Ali Nosrati ◽

Mohammad Khodaei ◽

Mehdi Banitalebi-Dehkordi ◽

...

Keyword(s):

Tissue Engineering ◽

Wound Healing ◽

Tissue Regeneration ◽

Molecular Mechanisms ◽

Healing Process ◽

The Body ◽

Key Factors ◽

Potential Applications ◽

Nanocomposite Scaffolds

AbstractSkin is the body’s first barrier against external pathogens that maintains the homeostasis of the body. Any serious damage to the skin could have an impact on human health and quality of life. Tissue engineering aims to improve the quality of damaged tissue regeneration. One of the most effective treatments for skin tissue regeneration is to improve angiogenesis during the healing period. Over the last decade, there has been an impressive growth of new potential applications for nanobiomaterials in tissue engineering. Various approaches have been developed to improve the rate and quality of the healing process using angiogenic nanomaterials. In this review, we focused on molecular mechanisms and key factors in angiogenesis, the role of nanobiomaterials in angiogenesis, and scaffold-based tissue engineering approaches for accelerated wound healing based on improved angiogenesis.

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