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Complex physical and chemical interactions take place in the interface between the implant surface and bone. Various descriptions of the ultrastructural arrangement to various implant ...design features, ranging from solid and macroporous geometries to surface modifications on the micron-, submicron-, and nano- levels, have been put forward. Here, the current knowledge regarding structural organisation of the bone-implant interface is reviewed with a focus on solid devices, mainly metal (or alloy) intended for permanent anchorage in bone. Certain biomaterials that undergo surface and bulk degradation are also considered. The bone-implant interface is a heterogeneous zone consisting of mineralised, partially mineralised, and unmineralised areas. Within the meso-micro-nano-continuum, mineralised collagen fibrils form the structural basis of the bone-implant interface, in addition to accumulation of non-collagenous macromolecules such as osteopontin, bone sialoprotein, and osteocalcin. In the published literature, as many as eight distinct arrangements of the bone-implant interface ultrastructure have been described. The interpretation is influenced by the in vivo model and species-specific characteristics, healing time point(s), physico-chemical properties of the implant surface, implant geometry, sample preparation route(s) and associated artefacts, analytical technique(s) and their limitations, and non-compromised vs compromised local tissue conditions. The understanding of the ultrastructure of the interface under experimental conditions is rapidly evolving due to the introduction of novel techniques for sample preparation and analysis. Nevertheless, the current understanding of the interface zone in humans in relation to clinical implant performance is still hampered by the shortcomings of clinical methods for resolving the finer details of the bone-implant interface.
Being a hierarchical material by design, the overall strength of bone is governed by composition and structure. Understanding the structure of the bone-implant interface is essential in the development of novel bone repair materials and strategies, and their long-term success. Here, the current knowledge regarding the eventual structural organisation of the bone-implant interface is reviewed, with a focus on solid devices intended for permanent anchorage in bone, and certain biomaterials that undergo surface and bulk degradation. The bone-implant interface is a heterogeneous zone consisting of mineralised, partially mineralised, and unmineralised areas. Within the meso-micro-nano-continuum, mineralised collagen fibrils form the structural basis of the bone-implant interface, in addition to accumulation of non-collagenous macromolecules such as osteopontin, bone sialoprotein, and osteocalcin.
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Critical-sized bone defect repair remains a substantial challenge in clinical settings and requires bone grafts or bone substitute materials. However, existing biomaterials often do ...not meet the clinical requirements of structural support, osteoinductive property, and controllable biodegradability. To treat large-scale bone defects, the development of three-dimensional (3D) porous scaffolds has received considerable focus within bone engineering. A variety of biomaterials and manufacturing methods, including 3D printing, have emerged to fabricate patient-specific bioactive scaffolds that possess controlled micro-architectures for bridging bone defects in complex configurations. During the last decade, with the development of the 3D printing industry, a large number of tissue-engineered scaffolds have been created for preclinical and clinical applications using novel materials and innovative technologies. Thus, this review provides a brief overview of current progress in existing biomaterials and tissue engineering scaffolds prepared by 3D printing technologies, with an emphasis on the material selection, scaffold design optimization, and their preclinical and clinical applications in the repair of critical-sized bone defects. Furthermore, it will elaborate on the current limitations and potential future prospects of 3D printing technology.
3D printing has emerged as a critical fabrication process for bone engineering due to its ability to control bulk geometry and internal structure of tissue scaffolds. The advancement of bioprinting methods and compatible ink materials for bone engineering have been a major focus to develop optimal 3D scaffolds for bone defect repair. Achieving a successful balance of cellular function, cellular viability, and mechanical integrity under load-bearing conditions is critical. Hybridization of natural and synthetic polymer-based materials is a promising approach to create novel tissue engineered scaffolds that combines the advantages of both materials and meets various requirements, including biological activity, mechanical strength, easy fabrication and controllable degradation. 3D printing is linked to the future of bone grafts to create on-demand patient-specific scaffolds.
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Porous biomaterials can be additively manufactured with micro-architecture tailored to satisfy the stringent mechano-biological requirements imposed by bone replacement implants. In a ...previous investigation, we introduced structurally porous biomaterials, featuring strength five times stronger than commercially available porous materials, and confirmed their bone ingrowth capability in an in vivo canine model. While encouraging, the manufactured biomaterials showed geometric mismatches between their internal porous architecture and that of its as-designed counterpart, as well as discrepancies between predicted and tested mechanical properties, issues not fully elucidated. In this work, we propose a systematic approach integrating computed tomography, mechanical testing, and statistical analysis of geometric imperfections to generate statistical based numerical models of high-strength additively manufactured porous biomaterials. The method is used to develop morphology and mechanical maps that illustrate the role played by pore size, porosity, strut thickness, and topology on the relations governing their elastic modulus and compressive yield strength. Overall, there are mismatches between the mechanical properties of ideal-geometry models and as-manufactured porous biomaterials with average errors of 49% and 41% respectively for compressive elastic modulus and yield strength. The proposed methodology gives more accurate predictions for the compressive stiffness and the compressive strength properties with a reduction of the average error to 11% and 7.6%. The implications of the results and the methodology here introduced are discussed in the relevant biomechanical and clinical context, with insight that highlights promises and limitations of additively manufactured porous biomaterials for load-bearing bone replacement implants.
In this work, we perform mechanical characterization of load-bearing porous biomaterials for bone replacement over their entire design space. Results capture the shift in geometry and mechanical properties between as-designed and as-manufactured biomaterials induced by additive manufacturing. Characterization of this shift is crucial to ensure appropriate manufacturing of bone replacement implants that enable biological fixation through bone ingrowth as well as mechanical property harmonization with the native bone tissue. In addition, we propose a method to include manufacturing imperfections in the numerical models that can reduce the discrepancy between predicted and tested properties. The results give insight into the use of structurally porous biomaterials for the design and additive fabrication of load-bearing implants for bone replacement.
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Recently accumulating evidence has put into question the role of large multinucleated giant cells (MNGCs) around bone biomaterials. While cells derived from the monocyte/macrophage ...lineage are one of the first cell types in contact with implanted biomaterials, it was originally thought that specifically in bone tissues, all giant cells were bone-resorbing osteoclasts whereas foreign body giant cells (FBGCs) were found associated with a connective tissue foreign body reaction resulting in fibrous encapsulation and/or material rejection. Despite the great majority of bone grafting materials routinely found with large osteoclasts, a special subclass of bone biomaterials has more recently been found surrounded by large giant cells virtually incapable of resorbing bone grafts even years after their implantation. While original hypotheses believed that a ‘foreign body reaction’ may be taking place, histological data retrieved from human samples years after their implantation have put these original hypotheses into question by demonstrating better and more stable long-term bone volume around certain bone grafts. Exactly how or why this ‘special’ subclass of giant cells is capable of maintaining long-term bone volume, or methods to scientifically distinguish them from osteoclasts remains extremely poorly studied. The aim of this review article was to gather the current available literature on giant cell markers and differences in expression patterns between osteoclasts and MNGCs utilizing 19 specific markers including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (previously referred to as FBGCs) as well as wound-healing M2-MNGCs is introduced and discussed.
This review article presents 19 specific cell-surface markers to distinguish between osteoclasts and MNGCs including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (often previously referred to as FBGCs) as well as wound-healing M2-MNGCs is introduced and discussed. The proposed concepts and guidelines aims to guide the next wave of research facilitating the differentiation between osteoclast/MNGCs formation, as well as provides the basis for increasing our understanding of the exact function of MNGCs in bone tissue/biomaterial homeostasis.
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Porous biomaterials that simultaneously mimic the topological, mechanical, and mass transport properties of bone are in great demand but are rarely found in the literature. In this ...study, we rationally designed and additively manufactured (AM) porous metallic biomaterials based on four different types of triply periodic minimal surfaces (TPMS) that mimic the properties of bone to an unprecedented level of multi-physics detail. Sixteen different types of porous biomaterials were rationally designed and fabricated using selective laser melting (SLM) from a titanium alloy (Ti-6Al-4V). The topology, quasi-static mechanical properties, fatigue resistance, and permeability of the developed biomaterials were then characterized. In terms of topology, the biomaterials resembled the morphological properties of trabecular bone including mean surface curvatures close to zero. The biomaterials showed a favorable but rare combination of relatively low elastic properties in the range of those observed for trabecular bone and high yield strengths exceeding those reported for cortical bone. This combination allows for simultaneously avoiding stress shielding, while providing ample mechanical support for bone tissue regeneration and osseointegration. Furthermore, as opposed to other AM porous biomaterials developed to date for which the fatigue endurance limit has been found to be ≈20% of their yield (or plateau) stress, some of the biomaterials developed in the current study show extremely high fatigue resistance with endurance limits up to 60% of their yield stress. It was also found that the permeability values measured for the developed biomaterials were in the range of values reported for trabecular bone. In summary, the developed porous metallic biomaterials based on TPMS mimic the topological, mechanical, and physical properties of trabecular bone to a great degree. These properties make them potential candidates to be applied as parts of orthopedic implants and/or as bone-substituting biomaterials.
Bone-substituting biomaterials aim to mimic bone properties. Although mimicking some of bone properties is feasible, biomaterials that could simultaneously mimic all or most of the relevant bone properties are rare. We used rational design and additive manufacturing to develop porous metallic biomaterials that exhibit an interesting combination of topological, mechanical, and mass transport properties. The topology of the developed biomaterials resembles that of trabecular bone including a mean curvature close to zero. Moreover, the developed biomaterials show an unusual combination of low elastic modulus to avoid stress shielding and high strength to provide mechanical support. The fatigue resistance of the developed biomaterials is also exceptionally high, while their permeability is in the range of values reported for bone.
The growing interest in multi-functional metallic biomaterials for bone substitutes challenges the current additive manufacturing (AM, =3D printing) technologies. It is foreseeable that advances in ...multi-material AM for metallic biomaterials will not only allow for complex geometrical designs, but also improve their multi-functionalities by tuning the types or compositions of the underlying base materials, thereby presenting unprecedented opportunities for advanced orthopedic treatments. AM technologies are yet to be extensively explored for the fabrication of multi-functional metallic biomaterials, especially for bone substitutes. The aim of this review is to present the viable options of the state-of-the-art multi-material AM for Ti-, Mg-, and Fe-based biomaterials to be used as bone substitutes. The review starts with a brief review of bone tissue engineering, the design requirements, and fabrication technologies for metallic biomaterials to highlight the advantages of using AM over conventional fabrication methods. Five AM technologies suitable for metal 3D printing are compared against the requirements for multi-material AM. Of these AM technologies, extrusion-based multi-material AM is shown to have the greatest potential to meet the requirements for the fabrication of multi-functional metallic biomaterials. Finally, recent progress in the fabrication of Ti-, Mg-, and Fe-based biomaterials including the utilization of multi-material AM technologies is reviewed so as to identify the knowledge gaps and propose the directions of further research for the development of multi-material AM technologies that are applicable for the fabrication of multi-functional metallic biomaterials.
Addressing a critical bone defect requires the assistance of multi-functional porous metallic bone substitutes. As one of the most advanced fabrication technology in bone tissue engineering, additive manufacturing is challenged for its viability in multi-material fabrication of metallic biomaterials. This article reviews how the current metal additive manufacturing technologies have been and can be used for multi-material fabrication of Ti-, Mg-, and Fe-based bone substitutes. Progress on the Ti-, Mg-, and Fe-based biomaterials, including the utilization of multi-material additive manufacturing, are discussed to direct future research for advancing the multi-functional additively manufactured metallic bone biomaterials.
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Biomaterials for Skin Substitutes Sheikholeslam, Mohammadali; Wright, Meghan E E; Jeschke, Marc G ...
Advanced healthcare materials,
03/2018, Volume:
7, Issue:
5
Journal Article
Peer reviewed
Open access
Patients with extensive burns rely on the use of tissue engineered skin due to a lack of sufficient donor tissue, but it is a challenge to identify reliable and economical scaffold materials and ...donor cell sources for the generation of a functional skin substitute. The current review attempts to evaluate the performance of the wide range of biomaterials available for generating skin substitutes, including both natural biopolymers and synthetic polymers, in terms of tissue response and potential for use in the operating room. Natural biopolymers display an improved cell response, while synthetic polymers provide better control over chemical composition and mechanical properties. It is suggested that not one material meets all the requirements for a skin substitute. Rather, a composite scaffold fabricated from both natural and synthetic biomaterials may allow for the generation of skin substitutes that meet all clinical requirements including a tailored wound size and type, the degree of burn, the patient age, and the available preparation technique. This review aims to be a valuable directory for researchers in the field to find the optimal material or combination of materials based on their specific application.
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The adsorption of proteins is the initiating event in the processes occurring when blood contacts a “foreign” surface in a medical device, leading inevitably to thrombus formation. ...Knowledge of protein adsorption in this context has accumulated over many years but remains fragmentary and incomplete. Moreover, the significance and relevance of the information for blood compatibility are not entirely agreed upon in the biomaterials research community. In this review, protein adsorption from blood is discussed under the headings “agreed upon” and “not agreed upon or not known” with respect to: protein layer composition, effects on coagulation and complement activation, effects on platelet adhesion and activation, protein conformational change and denaturation, prevention of nonspecific protein adsorption, and controlling/tailoring the protein layer composition.
This paper is part 2 of a series of 4 reviews discussing the problem of biomaterial associated thrombogenicity. The objective was to highlight features of broad agreement and provide commentary on those aspects of the problem that were subject to dispute. We hope that future investigators will update these reviews as new scholarship resolves the uncertainties of today.
Featured Cover: Cover Image, Volume 22, Issue 5 Chen, Long; Zhao, Ningjing; McClements, David J. ...
Comprehensive reviews in food science and food safety,
09/2023, Volume:
22, Issue:
5
Journal Article
Peer reviewed
Open access
The cover image is based on the Comprehensive Review Advanced dendritic glucan‐derived biomaterials: From molecular structure to versatile applications by Long Chen et al., ...https://doi.org/10.1111/1541-4337.13201.
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Hydrogels have been recognized as crucial biomaterials in the field of tissue engineering, regenerative medicine, and drug delivery applications due to their specific characteristics. ...These biomaterials benefit from retaining a large amount of water, effective mass transfer, similarity to natural tissues and the ability to form different shapes. However, having relatively poor mechanical properties is a limiting factor associated with hydrogel biomaterials. Controlling the biomechanical properties of hydrogels is of paramount importance. In this work, firstly, mechanical characteristics of hydrogels and methods employed for characterizing these properties are explored. Subsequently, the most common approaches used for tuning mechanical properties of hydrogels including but are not limited to, interpenetrating polymer networks, nanocomposites, self-assembly techniques, and co-polymerization are discussed. The performance of different techniques used for tuning biomechanical properties of hydrogels is further compared. Such techniques involve lithography techniques for replication of tissues with complex mechanical profiles; microfluidic techniques applicable for generating gradients of mechanical properties in hydrogel biomaterials for engineering complex human tissues like intervertebral discs, osteochondral tissues, blood vessels and skin layers; and electrospinning techniques for synthesis of hybrid hydrogels and highly ordered fibers with tunable mechanical and biological properties. We finally discuss future perspectives and challenges for controlling biomimetic hydrogel materials possessing proper biomechanical properties.
Hydrogels biomaterials are essential constituting components of engineered tissues with the applications in regenerative medicine and drug delivery. The mechanical properties of hydrogels play crucial roles in regulating the interactions between cells and extracellular matrix and directing the cells phenotype and genotype. Despite significant advances in developing methods and techniques with the ability of tuning the biomechanical properties of hydrogels, there are still challenges regarding the synthesis of hydrogels with complex mechanical profiles as well as limitations in vascularization and patterning of complex structures of natural tissues which barricade the production of sophisticated organs. Therefore, in addition to a review on advanced methods and techniques for measuring a variety of different biomechanical characteristics of hydrogels, the new techniques for enhancing the biomechanics of hydrogels are presented. It is expected that this review will profit future works for regulating the biomechanical properties of hydrogel biomaterials to satisfy the demands of a variety of different human tissues.
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