2D Boron Nanoplatelets as a Multifunctional Additive for Osteogenic, Gram‐Negative Antimicrobial and Mechanically Reinforcing Bone Repair Scaffolds

Osteoimmunomodulatory properties of magnesium scaffolds coated with β-tricalcium phosphate

A 3D-printed PLGA/HA composite scaffold modified with fusion peptides to enhance its antibacterial, osteogenic and angiogenic properties in bone defect repair

The effects of collagen concentration and crosslink density on the biological, structural and mechanical properties of collagen-GAG scaffolds for bone tissue engineering

Polylactic glycolic acid copolymer (PLGA) has been widely used in tissue engineering due to its good biocompatibility and degradation properties. However, the mismatched mechanical and unsatisfactory biological properties of PLGA limit further application in bone tissue engineering. Calcium sulfate (CaSO4) is one of the most promising bone repair materials due to its non-immunogenicity, well biocompatibility, and excellent bone conductivity. In this study, aiming at the shortcomings of activity-lack and low mechanical of PLGA in bone tissue engineering, customized-designed 3D porous PLGA/CaSO4 scaffolds were prepared by 3D printing. We first studied the physical properties of PLGA/CaSO4 scaffolds and the results showed that CaSO4 improved the mechanical properties of PLGA scaffolds. In vitro experiments showed that PLGA/CaSO4 scaffold exhibited good biocompatibility. Moreover, the addition of CaSO4 could significantly improve the migration and osteogenic differentiation of MC3T3-E1 cells in the PLGA/CaSO4 scaffolds, and the PLGA/CaSO4 scaffolds made with 20 wt.% CaSO4 exhibited the best osteogenesis properties. Therefore, calcium sulfate was added to PLGA could lead to customized 3D printed scaffolds for enhanced mechanical properties and biological properties. The customized 3D-printed PLGA/CaSO4 scaffold shows great potential for precisely repairing irregular load-bearing bone defects.

Recently, tissue engineering and regenerative medicine, especially bone tissue engineering and regenerative medicine have developed rapidly. Bone tissue engineering is a complicated and dynamic bone remodeling process that starts with recruitment and migration of osteoblasts and then regulates their proliferation, differentiation, and mineralization. Scaffold is typically biodegradable material that plays a crucial role as one of the three elements of bone tissue engineering and regenerative medicine. Bone scaffold provides the mechanical support during reformation and repair of damaged or diseased bone. For more than a decade, a large amount of research work has been carried out on the designing of scaffolds, processing techniques, performance assessment, and medical application. Significant progress has been made toward scaffold materials for structural support for desired osteogenesis and angiogenesis abilities. To date, depending on the advanced technologies, the bioresorbable scaffolds possess controlled porosity and high mechanical properties are possible used as bone scaffold. Natural bone has delicate architectural structure that spans nanoscale to macroscopic dimensions, which determine the unique mechanical properties of bone. The hierarchical structure of natural bone can be defined as a nanocomposite consisting of inorganic nanocrystalline hydroxyapatite (HA), organic components (mostly are collagens) and water. The outside proteins assemble together to form an extracellular matrix (ECM) with nanostructured which influences the adhesion, proliferation, differentiation, and mineralization of several cell types, such as bone lining cell, mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. To better mimic the nanostructure in natural ECM, many research groups over the past decade developed nano-based scaffolds (nanotubes, nanofibers, nanoparticles, and hydrogel) to resemble the ECM for promising candidates in replacing defective tissues. The high biomimetic properties and excellent mechanical features of nano-based scaffolds plays a vital role in stimulating cell adhesion and proliferation, as well as directing bone tissue formation through mimetic the nanometer dimension of natural bone tissue. Besides, mechanical properties are key factors for bone regeneration and bone local function. Nowadays, a large number of research groups have tried to manipulate the mechanical properties of scaffolds through designing the different nanosturctures, including nanofiber, nanoparticle, polymer matrices to mimic the nanocomposite structure of natural bone. These materials have highly stiffness, strength, and toughness properties that are promising in bone tissue engineering. Nanobiomaterials, especially inorganic nanobiomaterials, have excellent mechanical properties and biocompatibility, and are ideal for the preparation of scaffold materials for bone tissue engineering and regenerative medicine, showing a broad application prospect. In this article, we systematically review the application of inorganic nanomaterials, including hydroxyapatite, silicon-based nanomaterials, carbon-containing nanomaterials and several metal nanomaterials in bone tissue engineering and regenerative medicine. Although nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering, the application in the clinical regenerative engineering has limited. Currently, there are several limitations in regenerative strategies, including low efficient cellular proliferation, differentiation and mineralization, insufficient mechanical strength of scaffolds, and limited production of growth factors necessary for efficient osteogenesis. Therefore, there are still some issues on the nano-based scaffold should be cleared: (1) The interaction of nano-based scaffold and bioactive molecules, growth factors, and genetic material, (2) the biocomptibility, cytotoxicity, and biodegradation of nano-based scaffold, and (3) nano-based scaffold mechanical stability, cellular survival, and molecular mechanism of inducing bone formation. As the development of nanotechnology, ultimate translation to the clinical application may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases.

Bone biomaterials play a vital role in bone repair by providing the necessary substrate for cell adhesion, proliferation, and differentiation and by modulating cell activity and function. In past decades, extensive efforts have been devoted to developing bone biomaterials with a focus on the following issues: (1) developing ideal biomaterials with a combination of suitable biological and mechanical properties; (2) constructing a cell microenvironment with pores ranging in size from nanoscale to submicro- and microscale; and (3) inducing the oriented differentiation of stem cells for artificial-to-biological transformation. Here we present a comprehensive review of the state of the art of bone biomaterials and their interactions with stem cells. Typical bone biomaterials that have been developed, including bioactive ceramics, biodegradable polymers, and biodegradable metals, are reviewed, with an emphasis on their characteristics and applications. The necessary porous structure of bone biomaterials for the cell microenvironment is discussed, along with the corresponding fabrication methods. Additionally, the promising seed stem cells for bone repair are summarized, and their interaction mechanisms with bone biomaterials are discussed in detail. Special attention has been paid to the signaling pathways involved in the focal adhesion and osteogenic differentiation of stem cells on bone biomaterials. Finally, achievements regarding bone biomaterials are summarized, and future research directions are proposed.

Carbon nanotubes (CNT) are beneficent candidates for bone tissue engineering (BTE) applications, mostly because of their superior mechanical properties. Although the previous studies confirmed that single-walled carbon nanotubes (SWNTs) have significant effect on biomedical applications but there is no study reported the effect of SWNTs on properties of the PCL scaffolds for BTE applications. The purpose of this study was to evaluate the effect of aminefunctionalized single-walled carbon nanotubes (aSWNTs) on mechanical properties and in vitro behavior of Polycaprolacton (PCL) scaffolds. PCL as a biocompatible polymeric matrix was composited with different amounts (ranging from 0, 0.1, 0.2, 0.5 wt.%) of aSWNTs to enhance structural and functional properties of electrospun scaffolds. Attachment, proliferation, differentiation of rat bone marrow-derived mesenchymal stem cells (rMSCs) seeded onto the scaffolds was analyzed. The morphology and mechanical properties of the scaffolds were characterized using SEM and tensile test. The results indicated that the addition of aSWNTs heightened the tensile strength while bioactivity and degradation rate were increased. Also, the addition of aSWNTs has significantly amplified the electrical conductivity of PCL solution and resulted in the thinner fibers with more uniform size distribution. Attachment, proliferation and differentiation of rMSCs were significantly improved. Although the best mechanical property was achieved in the scaffold with 0.2 wt% aSWNT, but the composite scaffold with 0.5 wt% aSWNT significantly shows superior proliferation and differentiation of the rMSCs. Alkaline phosphatase activity demonstrated elevated differentiation of cells on nanocomposite scaffolds.

Large-sized bone defects are a great challenge in clinics and considerably impair the quality of patients' daily life. Tissue engineering strategies using cells, scaffolds, and bioactive molecules to regulate the microenvironment in bone regeneration is a promising approach. Zinc, magnesium, and iron ions are natural elements in bone tissue and participate in many physiological processes of bone metabolism and therefore have great potential for bone tissue engineering and regeneration. In this review, we performed a systematic analysis on the effects of zinc, magnesium, and iron ions in bone tissue engineering. We focus on the role of these ions in properties of scaffolds (mechanical strength, degradation, osteogenesis, antibacterial properties, etc.). We hope that our summary of the current research achievements and our notifications of potential strategies to improve the effects of zinc, magnesium, and iron ions in scaffolds for bone repair and regeneration will find new inspiration and breakthroughs to inspire future research.

Tunable mechanical properties of chitosan-based biocomposite scaffolds for bone tissue engineering applications: A review

The performance of bone tissue engineering scaffolds can be assessed through cell responses to scaffolds, including cell attachment, infiltration, morphogenesis, proliferation, differentiation, etc, which are determined or heavily influenced by the composition, structure, mechanical properties, and biological properties (e.g. osteoconductivity and osteoinductivity) of scaffolds. Although some promising 3D printing techniques such as fused deposition modeling and selective laser sintering could be employed to produce biodegradable bone tissue engineering scaffolds with customized shapes and tailored interconnected pores, effective methods for fabricating scaffolds with well-designed hierarchical porous structure (both interconnected macropores and surface micropores) and tunable osteoconductivity/osteoinductivity still need to be developed. In this investigation, a novel cryogenic 3D printing technique was investigated and developed for producing hierarchical porous and recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate (Ca-P) nanoparticle/poly(L-lactic acid) nanocomposite scaffolds, in which the Ca-P nanoparticle-incorporated scaffold layer and rhBMP-2-encapsulated scaffold layer were deposited alternatingly using different types of emulsions as printing inks. The mechanical properties of the as-printed scaffolds were comparable to those of human cancellous bone. Sustained releases of Ca2+ ions and rhBMP-2 were achieved and the biological activity of rhBMP-2 was well-preserved. Scaffolds with a desirable hierarchical porous structure and dual delivery of Ca2+ ions and rhBMP-2 exhibited superior performance in directing the behaviors of human bone marrow-derived mesenchymal stem cells and caused improved cell viability, attachment, proliferation, and osteogenic differentiation, which has suggested their great potential for bone tissue engineering.

Polylactic acid (PLA) based scaffolds have attained considerable attention in recent years for being used as biodegradable implants in bone tissue engineering (BTE), owing to their suitable biocompatibility and processability. Nevertheless, the mechanical properties, bioactivity and biodegradation rate of PLA need to be improved for practical application. In this investigation, PLA-xMn composite filaments (x = 0, 1, 3, 5 and 7 wt%) were fabricated, characterized, and used for 3D printing of scaffolds by the fused deposition modeling process. The effect of Mn addition on the thermal, physical, mechanical, and structural properties, as well as the degradability and cell viability of 3D printed scaffolds were investigated in details. The obtained results indicate that the PLA-Mn composite filaments exhibit higher chain mobility and melt flow index values, with lower cold crystallization temperature and a higher degree of crystallinity. This higher flowability led to lower dimensional accuracy of 3D printed scaffolds, but resulted in higher interlayer adhesion. It was found that the mechanical properties of composite scaffolds were remarkably enhanced with the addition of Mn particles. The incorporation of Mn particles also caused higher surface roughness and hydrophilicity, a superior biodegradation rate of the scaffolds as well as better biocompatibility, indicating a promising candidate for (BTE) applications.

Effect of polycaprolactone impregnation on the properties of calcium silicate scaffolds fabricated by 3D printing

Degradation mechanisms and acceleration strategies of poly (lactic acid) scaffold for bone regeneration

Polydopamine-coated biomimetic bone scaffolds loaded with exosomes promote osteogenic differentiation of BMSC and bone regeneration.

Over the last few years, biopolymers have attracted great interest in tissue engineering and regenerative medicine due to the great diversity of their chemical, mechanical, and physical properties for the fabrication of 3D scaffolds. This review is devoted to recent advances in synthetic and natural polymeric 3D scaffolds for bone tissue engineering (BTE) and regenerative therapies. The review comprehensively discusses the implications of biological macromolecules, structure, and composition of polymeric scaffolds used in BTE. Various approaches to fabricating 3D BTE scaffolds are discussed, including solvent casting and particle leaching, freeze-drying, thermally induced phase separation, gas foaming, electrospinning, and sol–gel techniques. Rapid prototyping technologies such as stereolithography, fused deposition modeling, selective laser sintering, and 3D bioprinting are also covered. The immunomodulatory roles of polymeric scaffolds utilized for BTE applications are discussed. In addition, the features and challenges of 3D polymer scaffolds fabricated using advanced additive manufacturing technologies (rapid prototyping) are addressed and compared to conventional subtractive manufacturing techniques. Finally, the challenges of applying scaffold-based BTE treatments in practice are discussed in-depth.