The bone adhesive is a clinical requirement for complicated bone fractures always articulated by surgeons. Applying glue is a quick and easy way to fix broken bones. Adhesives, unlike conventional ...fixation methods such as wires and sutures, improve healing conditions and reduce postoperative pain by creating a complete connection at the fractured joint. Despite many efforts in the field of bone adhesives, the creation of a successful adhesive with robust adhesion and appropriate bioactivity for the treatment of bone fractures is still in its infancy. Because of the resemblance of the body's humid environment to the underwater environment, in the latest decades, researchers have pursued inspiration from nature to develop strong bioactive adhesives for bone tissue. The aim of this review article is to discuss the recent state of the art in bone adhesives with a specific focus on biomimetic adhesives, their action mechanisms, and upcoming perspective. Firstly, the adhesive biomaterials with specific affinity to bone tissue are introduced and their rational design is studied. Consequently, various types of synthetic and natural bioadhesives for bone tissue are comprehensively overviewed. Then, bioinspired-adhesives are described, highlighting relevant structures and examples of biomimetic adhesives mainly made of DOPA and the complex coacervates inspired by proteins secreted in mussel and sandcastle worms, respectively. Finally, this article overviews the challenges of the current bioadhesives and the future research for the improvement of the properties of biomimetic adhesives for use as bone adhesives.
The aim of this review article is discussing the recent state of the art of bone adhesives with a specific focus on the biomimetic adhesive, their action mechanisms, and upcoming perspective. Display omitted
•Various types of synthetic and natural bioadhesives for bone are studied.•Bioinspired adhesives for bone tissue application are described.•Structures and various types of biomimetic adhesives for bone are highlighted.•Challenges of bioadhesives and future researches of biomimetic adhesives are discussed.
Abstract The rising incidence of bone disorders has resulted in the need for more effective therapies to meet this demand, exacerbated by an increasing ageing population. Bone tissue engineering is ...seen as a means of developing alternatives to conventional bone grafts for repairing or reconstructing bone defects by combining biomaterials, cells and signalling factors. However, skeletal tissue engineering has not yet achieved full translation into clinical practice as a consequence of several challenges. The use of additive manufacturing techniques for bone biofabrication is seen as a potential solution, with its inherent capability for reproducibility, accuracy and customisation of scaffolds as well as cell and signalling factor delivery. This review highlights the current research in bone biofabrication, the necessary factors for successful bone biofabrication, in addition to the current limitations affecting biofabrication, some of which are a consequence of the limitations of the additive manufacturing technology itself.
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•Yb-doped hydroxyapatite nanorod arrays deposit in magnetic chitosan scaffolds.•Interconnected macropores in the scaffolds support the in-growth of bone tissues.•Yb and SrFe12O19 ...dopants increase VEGFA expression for blood vessel formation.•Yb and SrFe12O19 dopants promote osteogenesis by activating BMP-2/Smad pathway.•MYbHA/CS nanohybrid scaffolds are a novel platform for bone defect healing.
Hydroxyapatite (HA) is a traditional bone repair material, but its poor osteogenic and angiogenic abilities hinder the clinical application for critical-sized bone defect healing. Herein, ytterbium-doped hydroxyapatite (YbHA) nanorod arrays in situ deposited in magnetic chitosan (CS) porous scaffolds, leading to create magnetic YbHA/CS (MYbHA/CS) nanohybrid scaffolds. We hypothesized that both magnetic SrFe12O19 nanoplates and Yb dopants in the functional scaffolds favored the osteogenesis and vascularization in bone defect regions. To prove the hypothesis, the osteogenic and angiogenic activities of MYbHA/CS scaffolds were investigated by using rat bone marrow mesenchymal stem cells (rBMSCs) and rat cranial defects as models. Fortunately, both the magnetic fields and Yb3+ ions as-derived from MYbHA/CS scaffolds remarkably up-regulated the expression of osteogenic-related genes by activating BMP-2/Smad pathway, and simultaneously increased the expression of vascular endothelial growth factor. In vivo rat cranial defect models further revealed that the combination effects between magnetic SrFe12O19 nanoplates and Yb dopants remarkably stimulated the in-growth of blood vessels and new bones into three-dimensional channels in the nanohybrid scaffolds. Hence, the modification of SrFe12O19 nanoplates and Yb dopants in bone scaffolds is a novel and promising strategy to accelerate bone defect healing.
Exposure of cells to externally applied magnetic fields or to scaffolding materials with intrinsic magnetic properties (magnetic actuation) can regulate several biological responses. Here, we ...generated novel magnetized nanocomposite hydrogels by incorporation of magnetic nanoparticles (MNPs) into polyethylene glycol (PEG)-based hydrogels containing cells from the stromal vascular fraction (SVF) of human adipose tissue. We then investigated the effects of an external Static Magnetic Field (SMF) on the stimulation of osteoblastic and vasculogenic properties of the constructs, with MNPs or SMF alone used as controls. MNPs migrated freely through and out of the material following the magnetic gradient. Magnetically actuated cells displayed increased metabolic activity. After 1 week, the enzymatic activity of Alkaline Phosphatase (ALP), the expression of osteogenic markers (Runx2, Collagen I, Osterix), and the mineralized matrix deposition were all augmented as compared to controls. With magnetic actuation, strong activation of endothelial, pericytic and perivascular genes paralleled increased levels of VEGF and an enrichment in the CD31+ cells population. The stimulation of signaling pathways involved in the mechanotransduction, like MAPK8 or Erk, at gene and protein levels suggested an effect mediated through the mechanical stimulation. Upon subcutaneous implantation in mice, magnetically actuated constructs exhibited denser, more mineralized and faster vascularized tissues, as revealed by histological and micro-computed tomographic analyses. The present study suggests that magnetic actuation can stimulate both the osteoblastic and vasculogenic potentials of engineered bone tissue grafts, likely at least partially by mechanically stimulating the function of progenitor cells.
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•Magnetic fields and materials regulate several cell biological responses.•Magnetized nanocomposites are generated from hydrogel and magnetic nanoparticles.•The constructs are seeded with stromal vascular fraction cells (SVFs).•Static magnetic fields stimulate osteo-vasculogenic properties of the SVFs.•Implanted constructs produce more mineralized and vascularized tissues in vivo.
Bone damage, due to congenital defects, trauma and sports-related injuries, has become a foremost health problem all over the world. The present study involves fabrication of a nanocomposite scaffold ...of graphene oxide (GO), gelatin and alginate, with an aim of enhancing bone regeneration. The effect of varying concentration of GO on the scaffold properties was also determined. The incorporation of GO enhanced the compressive strength of the nanocomposite scaffolds significantly compared to the gelatin-alginate (GA) scaffold which is without GO. High % swelling (~700%) of the nanocomposite scaffold indicates its high hydrophilicity, which is suitable for tissue engineering. Slow biodegradation (~30% in 28 days) indicates its suitability for bone regeneration. In vitro studies, by seeding MG-63 cells over the nanocomposite scaffolds, revealed an enhancement in cell attachment and proliferation as compared to the GA scaffold: this indicates the positive effect of the GO on the scaffold properties which, in turn, can enhance bone regeneration. Cell differentiation studies, with the mesenchymal stem cells seeded scaffolds, revealed higher expression of osteoblast transcription factors (Runx2 and Osteocalcin) and alkaline phosphatase activity―indicating the scaffold to be a good osteoinductive material. Thus, the nanocomposite scaffold will be a potential scaffold for bone tissue engineering.
The hydrogel composited hydroxyapatite (HAp) scaffold shown biomimetic extracellular matrix and osteogenic activity, which is a promising bone regeneration biomaterial. 3D printing has been widely ...used in fabrication of customized and complex bone regeneration scaffold. However, it is still a challenge to prepare high-precision HAp reinforced composites by digital light processing (DLP) printing that can effectively promote bone regeneration. In this study, shear-thinning gelatin methacrylamide (GelMA)/hydroxyapatite (HAp) composite inks were prepared to fabricate high-precision scaffolds by DLP printing for bone repair. Firstly, GelMA hydrogels with adjustable mechanical, rheological and printing properties were synthesized to screen hydrogel concentration and degree of substitution. Then carefully selected biocompatible dispersants to reduce the agglomeration of hydroxyapatite. The actual printing resolution of the GelMA/HAp porous composite scaffolds with excellent mechanical strength through DLP 3D printing was up to about 100 μm. In vitro, the 3D printed composite scaffold significantly promoted the adhesion and proliferation of osteoblasts, as well as promoted osteogenic differentiation. In vivo, the GelMA/HAp porous composite scaffolds showed excellent ability in accelerating the formation of new bone in rabbit skull defects. The GelMA/HAp porous composite scaffolds fabricated by the composite inks with good printability, mechanical properties and osteogenic activity have fascinating potential in bone repair application.
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Large bone defects, which occur due to various causes, have substantially affected people's health and quality of life. Bone tissue engineering (BTE) is a promising approach for ...repairing or replacing bone injuries. The aim of BTE scaffolds is to mimic the biological function and structure of the natural bone extracellular matrix (ECM), which provides a three-dimensional (3D) environment for cell adsorption, proliferation and differentiation. Significant advances in materials science, computer-aided design (CAD) and biomedical engineering have facilitated BTE scaffolds. This paper describes the requirements of BTE scaffolds and highlights the important role of additive manufacturing (AM) technologies in building bridges between biomaterials, CAD models and additives, and BTE scaffolds. It reviews various AM technologies that are used to fabricate BTE scaffolds. These technologies are divided into seven categories: (1) stereolithography (SLA), (2) powder bed fusion (PBF), (3) binder jetting (BJ), (4) material extrusion (ME), (5) material jetting (MJ), (6) volumetric printing (VP) and (7) 4D printing (4DP). The characteristics, raw materials, accuracy, cost, advantages and disadvantages of the AM technologies are discussed. Several recommendations for future research are presented.
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Trauma- and disease-related skeletal defects and illnesses are plaguing millions of people especially in an ageing globe. Recently, the convergence of additive manufacturing (AM) and ...bone tissue engineering (BTE) has opened up an era of “Personalized Bone Healthcare”, wherein “design”, “printing”, and “engineering” inputs are judiciously orchestrated to yield custom 3D architected (bio)scaffolds, per relevant AM paradigms, to address biological/pathological complexities of host tissues. In this review, a systematic overview of fundamental theories, recent advances, and future trends in this domain is provided. It starts with a general introduction to BTE and AM, followed by emergent topics, including: (i) the design and choices of biomaterials or bioinks for AM paradigms including acellular 3D printing, 3D bioprinting, 4D (bio)printing, and hierarchical printing; (ii) the utilization of computational tools, design–property relationships, and emerging metamaterial strategies to afford predictive, bionic or smart scaffold geometries; and (iii) the engineering of AM systems, processes, and printed parts, by hardware modification, technology fusion, or material functionalization. The ultimate goal is to produce (bio)scaffolds with customized/biomimetic form (geometry, hierarchy, heterogeneity, cellular microenvironments, etc.) and function. Subsequently, the state‐of‐the‐art orthopedic applications are summarized, covering interweaved frontiers of therapy and repair/regeneration. The convergence of AM and BTE as well as clinical translation are also discussed. Finally, current challenges and foreseeable opportunities are outlined to foster future growth. This panoramic review could provide helpful guidance for the design, development, and adoption of AM-based biomaterials for next-generation bone healthcare.
3D printed bone scaffolds have the potential to replace autografts and allografts because of advantages such as unlimited supply and the ability to tailor the scaffolds’ biochemical, biological and ...biophysical properties. Significant progress has been made over the past decade in additive manufacturing techniques to 3D print bone grafts, but challenges remain in the lack of manufacturing techniques that can recapitulate both mechanical and biological functions of native bones. The purpose of this review is to outline the recent progress and challenges of engineering an ideal synthetic bone scaffold and to provide suggestions for overcoming these challenges through bioinspiration, high-resolution 3D printing, and advanced modeling techniques. The article provides a short overview of the progress in developing the 3D printed scaffolds for the repair and regeneration of critical size bone defects.
Treatment of critical size bone defects is still a tremendous clinical challenge. To address this challenge, diverse sets of advanced manufacturing approaches and materials have been developed for bone tissue scaffolds. 3D printing has sparked much interest because it provides a close control over the scaffold's internal architecture and in turn its mechanical and biological properties. This article provides a critical overview of the relationships between material compositions, printing techniques, and properties of the scaffolds and discusses the current technical challenges facing their successful translation to the clinic. Bioinspiration, high-resolution printing, and advanced modeling techniques are discussed as future directions to address the current challenges.
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3D printing technology provides an excellent capability to manufacture customised implants for patients. Now, its applications are also successful in bone tissue engineering. This paper tries to ...provide a review of the applications of 3D printing in bone tissue engineering.
Searching by keywords, from the Scopus database, to identify relevant latest research articles on 3D printing in bone tissue engineering, through “3D printing” “bone tissue engineering”. This study makes a bibliometric analysis of the identified research articles and identified major applications and steps.
3D printing technology creates innovative development in bone tissue engineering. It involves the manufacturing of a scaffold with the combination of cells and materials. We identified a total number of 257 research articles through bibliometric analysis by searching through keywords “3D printing” “bone tissue engineering”. This paper studies 3D printing technology and its significant contributions, benefits and steps used for bone tissue engineering. Result discusses the essential elements of bone tissue engineering and identifies its five significant advancements when 3D printing is used. Finally, ten useful applications of 3D printing in bone tissue engineering are identified and studied with a brief description.
In orthopaedics, bone defects create a high impact on the quality of life of the patient. It leads to a higher demand for bone substitutes for replacement of bone defect. Bone tissue engineering can help to replace a critical defect bone. 3D printing is a useful technology for the fabrication of scaffolds critical in bone tissue engineering. There are different binders which can create bone scaffolds with requisite mechanical strength. These binders are used to create excellent osteoconductive, bioactive scaffolds. Computed tomography (CT) and Magnetic resonance imaging (MRI) help to provide images of specific defects of an individual patient, and these images can further be used for 3D printing the detective object. A bone defect caused by specific disease is sorted out by transplantation in clinical practice. Now a day bone tissue engineering opens a new option for this treatment of bone defects with the manufacturing of porous bone scaffold using 3D printing technology.
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