Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.

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Natural-based nanocomposites for bone tissue engineering and regenerative medicine: a review.

Bone defects requiring grafts to promote healing are frequently occurring and costly problems in health care. Chitosan, a biodegradable, naturally occurring polymer, has drawn considerable attention in recent years as a scaffolding material in tissue engineering and regenerative medicine. Chitosan is especially attractive as a bone scaffold material because it supports the attachment and proliferation of osteoblast cells as well as formation of mineralized bone matrix. In this review, we discuss the fundamentals of bone tissue engineering and the unique properties of chitosan as a scaffolding material to treat bone defects for hard tissue regeneration. We present common methods for fabrication and characterization of chitosan scaffolds, and discuss the influence of material preparation and addition of polymeric or ceramic components or biomolecules on chitosan scaffold properties such as mechanical strength, structural integrity, and functional bone regeneration. Finally, we highlight recent advances in the development of chitosan-based scaffolds with enhanced bone regeneration capability.

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Chitosan-based scaffolds for bone tissue engineering

As life expectancy increases, malfunction or loss of tissue caused by injury or disease leads to reduced quality of life in many patients at significant socioeconomic cost. Even though major progress has been made in the field of bone tissue engineering, present therapies, such as bone grafts, still have limitations. Current research on biodegradable polymers is emerging, combining these structures with osteogenic cells, as an alternative to autologous bone grafts. Different types of biodegradable materials have been proposed for the preparation of three-dimensional porous scaffolds for bone tissue engineering. Among them, natural polymers are one of the most attractive options, mainly due to their similarities with extracellular matrix, chemical versatility, good biological performance, and inherent cellular interactions. In this review, special attention is given to chitosan as a biomaterial for bone tissue engineering applications. An extensive literature survey was performed on the preparation of chitosan scaffolds and their in vitro biological performance as well as their potential to facilitate in vivo bone regeneration. The present review also aims to offer the reader a general overview of all components needed to engineer new bone tissue. It gives a brief background on bone biology, followed by an explanation of all components in bone tissue engineering, as well as describing different tissue engineering strategies. Moreover, also discussed are the typical models used to evaluate in vitro functionality of a tissue-engineered construct and in vivo models to assess the potential to regenerate bone tissue are discussed.

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Scaffolds based bone tissue engineering: the role of chitosan.

Drug loaded homogeneous electrospun PCL/gelatin hybrid nanofiber structures for anti-infective tissue regeneration membranes

Over the past several decades, we have witnessed significant progress in chitosan and chitin based nanostructured materials. The nanofibers from chitin and chitosan with appealing physical and biological features have attracted intense attention due to their excellent biological properties related to biodegradability, biocompatibility, antibacterial activity, low immunogenicity and wound healing capacity. Various methods, such as electrospinning, self-assembly, phase separation, mechanical treatment, printing, ultrasonication and chemical treatment were employed to prepare chitin and chitosan nanofibers. These nanofibrous materials have tremendous potential to be used as drug delivery systems, tissue engineering scaffolds, wound dressing materials, antimicrobial agents, and biosensors. This review article discusses the most recent progress in the preparation and application of chitin and chitosan based nanofibrous materials in biomedical fields.

Emerging chitin and chitosan nanofibrous materials for biomedical applications

The promotion of bone regeneration by nanofibrous hydroxyapatite/chitosan scaffolds by effects on integrin-BMP/Smad signaling pathway in BMSCs

Acetic-Acid-Mediated Miscibility toward Electrospinning Homogeneous Composite Nanofibers of GT/PCL

Engaging functional biomaterial scaffolds to regulate stem cell differentiation has drawn a great deal of attention in the tissue engineering and regenerative medicine community. In this study, biomimetic composite nanofibrous scaffolds of hydroxyapatite/chitosan (HAp/CTS) were prepared to investigate their capacity for inducing murine mesenchymal stem cells (mMSCs) to differentiate into the osteogenic lineage, in the absence and presence of an osteogenic supplementation (i.e., ascorbic acid, β-glycerol phosphate, and dexamethasone), respectively. Using electrospun chitosan (CTS) nanofibrous scaffolds as the control, cell morphology, growth, specific osteogenic genes expression, and quantified proteins secretion on the HAp/CTS scaffolds were sequentially examined and assessed. It appeared that the HAp/CTS scaffolds supported better attachment and proliferation of the mMSCs. Most noteworthy was that in the absence of the osteogenic supplementation, expression of osteogenic genes including collagen I (Col I), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteocalcin (OCN) were significantly upregulated in mMSCs cultured on the HAp/CTS nanofibrous scaffolds. Also increased secretion of the osteogenesis protein markers of alkaline phosphatase and collagen confirmed that the HAp/CTS nanofibrous scaffold markedly promoted the osteogenic commitment in the mMSCs. Moreover, the presence of osteogenic supplementation proved an enhanced efficacy of mMSC osteogenesis on the HAp/CTS nanofibrous scaffolds. Collectively, this study demonstrated that the biomimetic nanofibrous HAp/CTS scaffolds could support and enhance the adhesion, proliferation, and particularly osteogenic differentiation of the mMSCs. It also substantiated the potential of using biomimetic nanofibrous scaffolds of HAp/CTS for functional bone repair and regeneration applications.

https://iopscience.iop.org/article/10.1088/0957-4484/23/48/485102/pdf

Electrospun biomimetic scaffold of hydroxyapatite/chitosan supports enhanced osteogenic differentiation of mMSCs.

Electrospinning has emerged as an attractive technique for the fabrication of ultrafine fibers in micro-/nano-scale fineness. However, it is still a huge technological challenge in achieving aligned fibers and arrays due to the inherent chaotic motion of an electrospinning jet. We report herein a novel spinning approach termed stable jet electrospinning to offer a facile solution to the noted issue. It involves judiciously using an ultrahigh molecular weight poly(ethylene oxide) to formulate the viscoelasticity of a spinning dope such that a very long and stable jet can be formed during electrospinning. This consequently allows for readily collecting and fabricating individual fibers, multi-filament yarns, well-aligned unidirectional fiber arrays in a large area, and ordered fiber patterns by controlling fiber placement. Our approach could thus open up the possibility of achieving continuous aligned ultrafine fibers and structures in a straightforward and scalable fashion, suitable for a variety of practical applications.

Stable jet electrospinning for easy fabrication of aligned ultrafine fibers

The invention relates to a preparation method of superfine oriented polymer fibers through stable jet-flow electrically driven spinning, comprising the following steps: dissolving macromolecular polymers in a solvent to obtain a spinning solution, and carrying out stable jet-flow electrically driven spinning on the spinning solution to obtain the superfine oriented polymer fibers. The preparationmethod is characterized in that the spinning solution contains a viscoelasticity improver which improves the viscoelasticity of the spinning solution and the stability of jet flows, so that the electro-spinning technology depending on the drive of an electric field force can be used for conveniently obtaining a single superfine fiber as well as a unidirectional fiber bundle and a unidirectional fiber film with higher orientation degree. The superfine fibers prepared in the invention have the advantages of higher macromolecular chain orientation degree and better mechanical property, and a fiber monofilament prepared in the invention has a smaller diameter capable of reaching 1-10mu m.

Hongju Peng

Papers

The promotion of bone regeneration by nanofibrous hydroxyapatite/chitosan scaffolds by effects on integrin-BMP/Smad signaling pathway in BMSCs

Acetic-Acid-Mediated Miscibility toward Electrospinning Homogeneous Composite Nanofibers of GT/PCL

Electrospun biomimetic scaffold of hydroxyapatite/chitosan supports enhanced osteogenic differentiation of mMSCs.

Stable jet electrospinning for easy fabrication of aligned ultrafine fibers

Preparation method of superfine oriented polymer fibers through stable jet-flow electrically driven spinning