Scaffolds For Bone Tissue Engineering Research Articles

Design and evaluation of TPMS-inspired 3D-printed scaffolds for bone tissue engineering: Enabling tailored mechanical and mass transport properties

Bone scaffolds in tissue engineering are used to provide mechanical support and facilitate bone regeneration. For this, mechanical and mass transport properties are of critical importance, yet compromised, to scaffold performance and remain to be solved. Herein, we propose novel strut-based scaffolds and design strategies that enable independent tailoring of topological, mechanical and mass transport properties. Scaffolds with different design parameters were characterized in terms of mechanical and mass transport properties through simulation analysis, and then they were fabricated by 3D printing for experimental verification. The simulation and experimental results showed that the proposed scaffolds exhibit controllable deformation modes and mass transport characteristics. The elastic modulus (0.58–4.12 GPa) and permeability (0.96 × 10−7-3.47 × 10−7 m2) of the designed structures fully meet the range of cancellous bone in existing literature. Moreover, we demonstrated that our designs enable scaffolds to decouple and individually tailor multi-physics properties at a given porosity, thus expanding the performance regulation space and providing guidance for designing scaffolds with desired properties.

The influence of rheology in the fabrication of ceramic-based scaffold for bone tissue engineering

Abstract Bone tissue is the second most affected organ in the human body after blood. Tissue engineering is the area whereby a scaffold is used to regenerate the lost bone. However, the scaffold’s effectiveness is primarily based on the material and the fabrication process. The patient-specific structures are affected because of the fabrication process used to fabricate the scaffold as per requirement. In this regard, rheology plays an important role in the fabrication of the patient-specific scaffold, and it is a study of the flow of ink. This primarily affects both the conventional as well as the non-conventional fabrication processes. In this paper, the scaffold and bone tissue engineering, the different fabrication processes, and the importance of the rheological characterization are presented. In addition to this, the rheological properties of the developed HA/β-TCP composite slurry are evaluated for the extrusion-based additive manufacturing process. The developed ink’s rheological properties show that the flow behavior index of about 0.0497 ± 0.009, minimum flow stress required to make the ink flow of about 51.076 Pa at a strain rate of 0.111 %, and shape retention upto 75 % after 175 s are obtained. Also, different orientations are 3D printed using the developed slurry.

Nuciferine-loaded chitosan hydrogel-integrated 3D-printed polylactic acid scaffolds for bone tissue engineering: A combinatorial approach

Critical-sized bone defects resulting from severe trauma and open fractures cannot spontaneously heal and require surgical intervention. Limitations of traditional bone grafting include immune rejection and demand-over-supply issues leading to the development of novel tissue-engineered scaffolds. Nuciferine (NF), a plant-derived alkaloid, has excellent therapeutic properties, but its osteogenic potential is yet to be reported. Furthermore, the bioavailability of NF is obstructed due to its hydrophobicity, requiring an efficient drug delivery system, such as chitosan (CS) hydrogel. We designed and fabricated polylactic acid (PLA) scaffolds via 3D printing and integrated them with NF-containing CS hydrogel to obtain the porous biocomposite scaffolds (PLA/CS-NF). The fabricated scaffolds were subjected to in vitro physicochemical characterization, cytotoxicity assays, and osteogenic evaluation studies. Scanning electron microscopic studies revealed uniform pore size distribution on PLA/CS-NF scaffolds. An in vitro drug release study showed a sustained and prolonged release of NF. The cyto-friendly nature of NF in PLA/CS-NF scaffolds towards mouse mesenchymal stem cells (mMSCs) was observed. Also, cellular and molecular level studies signified the osteogenic potential of NF in PLA/CS-NF scaffolds on mMSCs. These results indicate that the PLA/CS-NF scaffolds could promote new bone formation and have potential applications in bone tissue engineering.

Fabrication of BioMIL-4/Chitosan/Alginate-Based Nanocomposite Scaffolds for Bone Tissue Engineering

Fabrication of BioMIL-4/Chitosan/Alginate-Based Nanocomposite Scaffolds for Bone Tissue Engineering

Dual siRNA-Loaded Cell Membrane Functionalized Matrix Facilitates Bone Regeneration with Angiogenesis and Neurogenesis.

Vascularization and innervation play irreplaceable roles in bone regeneration and bone defect repair. However, the reconstruction of blood vessels and neural networks is often neglected in material design. This study aims to design a genetically functionalized matrix (GFM) and enable it to regulate angiogenesis and neurogenesis to accelerate the process of bone defect repair. The dual small interfering RNA (siRNA)-polyvinylimide (PEI)(siRP) complexes that locally knocked down soluble vascular endothelial growth factor receptor 1 (sFlt-1) and p75 neurotrophic factor receptor (p75NTR ) are prepared. The hybrid cell membrane (MM) loaded siRP is synthesized as siRNA@MMs to coat on polylactone (PCL) electrospun fibers for mimicking the natural bone matrix. The results indicates that siRNA@MMs could regulate the expression of vascular-related and neuro-related cytokines secreted by mesenchymal stem cells (MSCs). GFMs promote the expression of osteogenic differentiation through paracrine function in vitro. GFMs attenuates inflammation and promotes osseointegration by regulating the coupling of vascularization and innervation in vivo. This study uses the natural hybrid cell membrane to carry genetic material and assist in the vascularization and innervation function of two siRNA. The results present the significance of neuro-vascularized organoid bone and may provide a promising choice for the design of bone tissue engineering scaffold.

Research progress in degradable metal‐based multifunctional scaffolds for bone tissue engineering

AbstractThe increasing prevalence of orthopedic‐related diseases necessitates the development of effective orthopedic implants. Conventional metal scaffolds used in orthopedic devices have limitations such as poor biocompatibility and the need for a second surgery to remove the scaffold. Degradable metal‐based scaffolds, including metal‐based scaffolds and multifunctional scaffolds doped with metal elements, are a rapidly developing tissue engineering strategy aimed at utilizing the mechanical and biological properties of metal elements to create a support structure that matches the complex bone regeneration environment. Repairing bone defects involves the regeneration of various tissues, and incomplete repair can negatively affect bone function and overall recovery. Therefore, combining metal‐based degradable materials with other active components has great potential for enhancing the versatility and clinical applications of scaffolds. Multifunctional scaffolds doped with metal elements have better biocompatibility, osteoinductivity, biodegradability, matching mechanical, and microenvironmental adjustment capabilities. Moreover, these metal‐doped scaffolds possess the advantages of controlled release of metal ions, multifunctionality, and faster degradation. This review focuses on the materials and techniques used for constructing degradable metal‐based scaffolds. Furthermore, this study discussed the potential for designing and constructing multifunctional biodegradable metal‐based scaffolds doped with metal elements by integrating multiple strategies.

Novel barium-doped-baghdadite incorporated PHBV-PCL composite fibrous scaffolds for bone tissue engineering

Bioceramic/polymer composites have dragged a lot of attention for treating hard tissue damage in recent years. In this study, we synthesized barium-doped baghdadite (Ba-BAG), as a novel bioceramic, and later developed fibrous composite poly (hydroxybutyrate) co (hydroxyvalerate)- polycaprolactone (PHBV-PCL) scaffolds containing different amounts of baghdadite (BAG) and Ba-BAG, intended to be used in bone regeneration. Our results demonstrated that BAG and Ba-doped BAG powders were synthesized successfully using the sol-gel method and their microstructural, physicochemical, and cytotoxical properties results were evaluated. In the following, PHBV/PCL composite scaffolds containing different amounts of BAG and Ba-BAG (1, 3, and 5 wt%) were produced by the wet electrospinning method. The porosity of scaffolds decreased from 78% to 72% in Ba-BAG-incorporated PHBV/PCL scaffolds. The compressive strength of the scaffolds was between 4.69 and 9.28 kPa, which was increased to their maximum values in the scaffolds with Ba-BAG. The presence of BAG and Ba-BAG in the polymer scaffolds resulted in increasing bioactivity, and it was introduced as a suitable way to control the degradation rate of scaffolds. The presence of the BAG component was a major reason for higher cell proliferation in reinforced PHBV/PCL polymeric scaffolds, while Ba existence played its influential role in the higher osteogenic activity of cells on Ba-BAG incorporated PHBV/PCL scaffolds. Thus, the incorporation of Ba-BAG bioceramic materials into the structure of polymeric PHBV/PCL scaffolds promoted their various properties, and allow these scaffolds to be used as promising candidates in bone tissue engineering applications.

Geometrical and mechanical analysis of polylactic acid and polyvinylidine fluoride scaffolds for bone tissue engineering

Utilising finite element analyses and experimental testing, this study investigates the influence of scaffold porosity on mechanical behaviour and evaluates the potential of polylactic acid (PLA) and polyvinylidine fluoride (PVDF) as bone substitute materials. Scaffold geometries were devised using design parameters adapted from extant literature and then generated using computer-aided engineering tools. Methodical variations in strand thickness were applied, maintaining other design criteria constant for robust analysis. Results, derived under varied loading conditions, suggest that scaffold mechanical properties are influenced significantly by geometry, strand diameter and porosity. Cubic scaffolds exhibited marked strength. Structures with reduced porosity demonstrated heightened mechanical characteristics, while facilitating bone cell proliferation. For a comparative context, PVDF scaffolds were benchmarked against human femur bone properties, revealing a mechanical behaviour alignment, particularly in their Young’s modulus.

Bioactive Glasses Enriched with Strontium or Zinc with Different Degrees of Structural Order as Components of Chitosan-Based Composite Scaffolds for Bone Tissue Engineering.

The development of innovative biomaterials with improved integration with bone tissue and stimulating regeneration processes is necessary. Here, we evaluate the usefulness of bioactive glasses from the SiO2-P2O5-CaO system enriched with 2 wt.% SrO or ZnO in the manufacturing of chitosan-based scaffolds. Bioglasses produced using the sol-gel method were subjected to thermal treatment in different regimes. Chitosan/bioglass composites were produced with a weight ratio. Bioglasses were evaluated via TG-DTA, FTIR, and SEM-EDS before and after incubation in simulated body fluid (SBF). The release of ions was tested. The cytocompatibility of the composites in contact with MG63 osteoblast-like cells was evaluated. The results showed that the presence of the crystalline phase decreased from 41.2-44.8% for nonmodified bioglasses to 24.2-24.3% for those modified with ZnO and 22.0-24.2% for those modified with SrO. The samples released Ca2+, Zn2+, and/or Sr2+ ions and were bioactive according to the SBF test. The highest cytocompatibility was observed for the composites containing nonmodified bioglasses, followed by those enriched with SrO bioglasses. The least cytocompatible were the composites containing ZnO bioglasses that released the highest amount of Zn2+ ions (0.58 ± 0.07 mL/g); however, those that released 0.38 ± 0.04 mL/g were characterised by acceptable cytocompatibility. The study confirmed that it is feasible to control the biological performance of chitosan/bioglass composites by adjusting the composition and heat treatment parameters of bioglasses.

Three-Dimensional Printed Poly (Lactic-co-Glycolic Acid)-Magnesium Composite Scaffolds for the Promotion of Osteogenesis Through Immunoregulation.

Scaffolds play an important role in bone tissue engineering. The ideal engineered scaffold needs to be biocompatible, bioactive, and able to regulate immune cells to enhance bone regeneration. In this study, magnesium (Mg)-contained poly(lactic-co-glycolic acid) (PLGA) scaffolds (hereinafter, referred to as PLGA-2Mg) were fabricated by 3-dimensional printing using a mixture of PLGA and MgSO 4 powder. Poly(lactic-co-glycolic acid) scaffolds (hereinafter, referred to as PLGA) were also fabricated by 3-dimensional printing and were used as control. The biocompatibility, immunoregulatory ability, and osteogenic properties of PLGA-2Mg were analyzed and compared with those of PLGA. The results indicate that the incorporation of Mg increased the Young modulus and surface roughness of the scaffold, but did not affect its degradation. The PLGA-2Mg further promoted the adhesion and proliferation of MC3T3-E1 cells compared with PLGA, which indicates its improved biocompatibility and bioactivity. In addition, PLGA-2Mg inhibited the polarization of RAW 264.7 cells toward the M1 phenotype by down-regulating the IL-1β , IL-6 , and iNOs gene expression when challenged with lipopolysaccharide stimulation. In contrast, it promoted the polarization of RAW 264.7 cells toward the M2 phenotype by up-regulating the TGF-β , IL-10 , and Arg-1 gene expression without lipopolysaccharide stimulation. Finally, MC3T3-E1 cells were cocultured with RAW 264.7 cells and scaffolds using a transwell system. It was found that the expression level of osteogenic-related genes ( ALP , COL-1 , BMP2 , and BSP ) was significantly upregulated in the PLGA-2Mg group compared with that in the PLGA group. Consequently, PLGA-2Mg with increased biocompatibility and bioactivity can promote osteogenesis through immunoregulation and has the potential to be used as a novel scaffold in bone tissue engineering.

Fused Deposition Modeling Printed PLA/Nano β-TCP Composite Bone Tissue Engineering Scaffolds for Promoting Osteogenic Induction Function.

Large bone defects caused by congenital defects, infections, degenerative diseases, trauma, and tumors often require personalized shapes and rapid reconstruction of the bone tissue. Three-dimensional (3D)-printed bone tissue engineering scaffolds exhibit promising application potential. Fused deposition modeling (FDM) technology can flexibly select and prepare printed biomaterials and design and fabricate bionic microstructures to promote personalized large bone defect repair. FDM-3D printing technology was used to prepare polylactic acid (PLA)/nano β-tricalcium phosphate (TCP) composite bone tissue engineering scaffolds in this study. The ability of the bone-tissue-engineered scaffold to repair bone defects was evaluated in vivo and in vitro. PLA/nano-TCP composite bone tissue engineering scaffolds were prepared using FDM-3D printing technology. The characterization data of the scaffolds were obtained using relevant detection methods. The physical and chemical properties, biocompatibility, and in vitro osteogenic capacity of the scaffolds were investigated, and their bone repair capacity was evaluated using an in vivo animal model of rabbit femur bone defects. The FDM-printed PLA/nano β-TCP composite scaffolds exhibited good personalized porosity and shape, and their osteogenic ability, biocompatibility, and bone repair ability in vivo were superior to those of pure PLA. The merits of biodegradable PLA and bioactive nano β-TCP ceramics were combined to improve the overall biological performance of the composites. The FDM-printed PLA/nano-β-TCP composite scaffold with a ratio of 7:3 exhibited good personalized porosity and shape, as well as good osteogenic ability, biocompatibility, and bone repair ability. This study provides a promising strategy for treating large bone defects.

Nanostructured Porous Silicon for Bone Tissue Engineering: Kinetics of Particle Degradation and Si-Controlled Release.

Nanostructured porous silicon (pSi) is a synthetic silicon-based material. Its biocompatibility and bioresorbability in body fluids make pSi an appealing biomaterial for tissue engineering, with surfaces characteristics facilitating human cell adhesion and differentiation. The resorption kinetics of such porous biomaterials is crucial for in vivo bone regeneration, in order to adapt biomaterial resorption to tissue formation, and to control the release of loaded bioactive molecules. We investigated pSi as a bioactive scaffold for bone tissue engineering, with an emphasis on kinetics of pSi resorption and silicon release. PSi particles and chips were fabricated from crystalline silicon, and functionalized by oxidation and chemical grafting of amine groups to mimic biological structures. Materials resorption over time was investigated with Raman spectroscopy, infrared spectroscopy, and Scanning Electron Microscopy. Silicon release was followed by mass spectrometry. Particle degradation and inclusion in newly formed bone were studied in vivo. The in vitro experiments revealed that non-oxidized pSi had an accelerated initial dissolution in ddH2O and an inhibition of initial Si release in SBF. This high reactivity also led to transformation towards amorphous non-resorbable silica when incubated in SBF. PSi resorption started immediately with a maximal dissolution in the first 24 h. Later, the dissolution rate decreased over time. In comparison, the resorption process of oxidized pSi seemed delayed, but more continuous. This delayed dissolution increased the bioactivity and stability, leading to enhanced bone formation in vivo. Delayed pSi degradation provided a constant surge of silicic acid over time and promoted bone regeneration, demonstrating the high potential of pSi for bone tissue engineering: Oxidized pSi were almost completely resorbed after 2 months of healing, with remaining partially dissolved particles surrounded by newly formed bone. On the contrary, non-oxidized particles were still obviously present after 2 months with limited bone regeneration. This delayed resorption is consistent with the in vitro observations in SBF, and particles' transformation towards silica.

3D printed polylactide‐based zirconia‐toughened alumina composites: fabrication, mechanical, and in vitro evaluation

AbstractFused deposition modeling (FDM) has been a commonly used technique in the fabrication of geometrically complex biodegradable scaffolds for bone tissue engineering. Generally, either individual polylactide (PLA) or its combination with calcium phosphates or bioglass has been employed to design scaffolds through the principles of FDM. In this study, FDM protocol has been employed to design 3D printed PLA/zirconia‐toughened alumina (ZTA). A series of PLA/ZTA combinations have been attempted to determine the feasibility of the resultant in filament extrusion and their subsequent capacity to obtain a stable 3D printed component. A maximum of 80 wt.% PLA and 20 wt.% ZTA has been determined as an optimum combination to yield a stable 3D structure beyond which an enhanced ZTA content in the PLA matrix yielded a fragile filament that lacked effectiveness in 3D printing. 5 and 10 wt.% of ZTA addition in the PLA matrix produced a better 3D design that reasonably displayed good mechanical properties. Depending on the ceramic content, a homogeneous dispersion of the constituent elements representative of ZTA has been determined throughout the PLA matrix. Simulation studies through finite element analysis (FEA) exhibited good corroboration with the test results obtained from the mechanical studies.

Structural and topological design of conformal bilayered scaffolds for bone tissue engineering

A fundamental outcome of bone tissue engineering is the regeneration of bone defects presenting large dimensions. A promising solution in biomedical practice is the implantation of biomimetic scaffolds, i.e. porous structures mimicking the natural shapes of healthy bone tissues, which are colonized by mesenchymal stem cells and that support the growth of the regenerating tissues, until the complete healing process is realized. This work presented a workflow for the geometrical modeling and the mechanical design of beam-based, bilayered, and conformal scaffolds, mimicking the human cortico-cancellous bone structure for filling a large dimension defect in the mandibular bone of an injured patient. An isotropic Voronoi topology built on a refined point set generated by a high-quality meshing algorithm was adopted for lattice generation, which led to an open-cell architecture characterized by full connectivity and uniform cell size. Such geometrical and structural features represent crucially important requirements for maximizing the osteointegration and the vascularization of the implanted scaffold. An irregular scaffold was modelled, including a cortical and a sponge layer. The beam radii of both layers were determined by matching the elastic properties of the corresponding bone tissues, thus minimizing the stress shielding effects. Interestingly, several scaffold properties deriving from the proposed procedure, such as the porosity and the pore size, were in good agreement with those reported in the literature.

Application of Mineralized Chitosan Scaffolds in Bone Tissue Engineering

Chitosan (CS) is a natural cationic polysaccharide obtained via the N-deacetylation of chitin. It has various outstanding biological properties such as nontoxicity, biodegradability, biocompatibility, and antimicrobial properties. Minerals can be deposited on the CS template using different methods to construct composites with structures and functions similar to those of natural bone tissue. These ideal scaffolds can produce bone via osteogenesis, osteoinduction, and osteoconduction, with good biocompatibility and mechanical properties, and are thus considered promising novel biomaterials for repairing hard tissue defects. In the last decade, the field of mineralized CS scaffolds has provided novel fundamental knowledge and techniques to better understand the aforementioned fascinating phenomenon. This study mainly focused on the basic structures and properties of mineralized CS scaffolds to understand the current research progress and explore further development. Further, it summarizes the types, preparation methods, components, properties, and applications of mineralized CS scaffolds in bone tissue engineering during the last 5 years. The defects and shortcomings of the scaffolds are discussed, and possible improvement measures are put forward. We aimed to provide complete research progress on mineralized CS scaffolds in bone tissue engineering for researchers and clinicians, and also ideas for the next generation of mineralized CS scaffolds.

Evaluation of human amnion denuded derived mesenchymal stem cell on 3D porous hydroxyapatite composite scaffolds for osteogenic differentiation: Prolonged in vitro study

Recent studies using composite porous scaffolds have globally demonstrated the biocompatibility of mesenchymal stem cell sources. It is especially important in hard tissue bioengineering due to its desirable features and stemness effectivity. This study has emphasized primarily the evaluation of the morphological aspects of human amnion-denuded derived mesenchymal stem cells (hAMMSC) in combination with the fabrication of three-dimensional (3D) porous hydroxyapatite (Hap) composite scaffolds for bone tissue engineering based on the principal component of bone mineralization. We presented a novel combination of hAMMSC and nano-crystalline powder hydroxyapatite/bioactive glass (Hap/BG) composite scaffolds fabricated through the hydrothermal method via a novel formulation method from a previous study of stem cell in vitro prolonged culture. The 3D porous scaffold, 6 mm in size, was fabricated from 70 nm nanocrystalline powder and interacted with hAMMSC cultured in osteo-inductive conditions for 30 days. The characterization of 3D porous scaffolds was analyzed via Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) to explore the particle structure, morphology, bioactivity, and porosity of the composite powder and scaffolds in contact with hAMMSCs culture. Furthermore, biocompatibility was assessed using the PrestoBlueTM viability assay and scanning electron microscopy observation (SEM), which revealed the attachment, morphology, and spreading of hAMMSCs on the 3D porous scaffolds of Hap/BG by showing spindle-like morphology and forming the spreading filopodia bridge-like structure within the scaffolds. Subsequently, the secondary objective is the characterization of human AMMSC differentiation capacity assessed by early osteoblast differentiation and mineralization behaviour investigated by early detected assay via alkaline phosphatase activity (ALP) activity marker and energy dispersive X-ray (EDX) analysis simultaneously of the mineralization within bone matrix elements. It was comparatively evaluated via ALP and EDX for calcium quantification elements. Immunomodulatory properties were analyzed via ELISA kits. In conclusion, our findings indicate that 3D porous scaffolds made of Hap/BG composites could be great candidates for future regenerative medicine applications due to their support towards stem cell growth and enhancement of bone cell capacity.

Effect of Porosity and Pore Shape on the Mechanical and Biological Properties of Additively Manufactured Bone Scaffolds.

This study investigates the effect of porosity and pore shape on the biological and mechanical behavior of additively manufactured scaffolds for bone tissue engineering (BTE). Polylactic acid scaffolds with varying porosity levels (15-78%) and pore shapes, including regular (rectangular pores), gyroid, and diamond (triply periodic minimal surfaces) structures, are fabricated by fused filament fabrication. Murine-derived macrophages and human bone marrow-derived mesenchymal stromal cells (hBMSCs) are seeded onto the scaffolds. The compressive behavior and surface morphology of the scaffolds are characterized. The results show that scaffolds with 15%, 30%, and 45% porosity display the highest rate of macrophage and hBMSC growth. Gyroid and diamond scaffolds exhibit a higher rate of macrophage proliferation, while diamond scaffolds exhibit a higher rate of hBMSC proliferation. Additionally, gyroid and diamond scaffolds exhibit better compressive behavior compared to regular scaffolds. Of particular note, diamond scaffolds have the highest compressive modulus and strength. Surface morphology characterization indicates that the surface roughness of diamond and gyroid scaffolds is greater than that of regular scaffolds at the same porosity level, which is beneficial for cell attachment and proliferation. This study provides valuable insights into porosity and pore shape selection for additively manufactured scaffolds in BTE.

Ti6Al4V biomimetic scaffolds for bone tissue engineering: Fabrication, biomechanics and osseointegration

The design of porous structure that mimic trabecular bone is an effective method for optimizing the elastic modulus and osseointegration properties of titanium alloy implants. However, there is no consensus on which structure is best. In this study, we fabricated 24 different types of Ti6Al4V trabecular bone scaffolds with varying porosity and average pore size using Voronoi algorithm and selective laser melting technology. The biomechanics and osseointegration properties were studied by mechanical tests, computational fluid dynamics, cell and animal experiments. Our results showed that with an increase of porosity and average pore size, the scaffold's yield strength, ultimate strength, elastic modulus and shear stress exhibited an overall decreasing trend while the permeability and nutrient transport improved. Cell experiments showed that reducing the average pore size enhanced the adhesion and proliferation of MC3T3-E1 cells when the porosity was constant. Animal experiments showed that the scaffold with 65% porosity and 550 μm pore size had the most significant new bone formation effect. Based on our research results, we concluded that a porous structure design with 65% porosity and an average pore size of 550 μm, resembling bone trabecular, had the most significant effect on enhancing the comprehensive performance of titanium alloy implants.

Proliferation and differential regulation of osteoblasts cultured on surface-phosphorylated cellulose nanofiber scaffolds

Phosphorus-containing polymers have received much attention for their excellent ability to regulate bone cell differentiation and calcification. Given the increasing concern about environmental issues, it is promising to utilize “green” biomaterials to construct novel cell culture scaffolds for bone tissue engineering. Herein, surface-phosphorylated cellulose nanofibers (P-CNFs) were fabricated as a novel green candidate for osteoblast culture. Compared with native CNF, P-CNFs possessed shorter fiber morphology with tunable phosphate group content (0–1.42 mmol/g). The zeta-potential values of CNFs were enhanced after phosphorylation, resulting in the formation of uniform and stable scaffolds. The cell culture behavior of mouse osteoblast (MC3T3-E1) cells showed a clear phosphate content-dependent cell proliferation. The osteoblast cells adhered well and proliferated efficiently on P-CNF0.78 and P-CNF1.05, with phosphate contents of 0.78 and 1.05 mmol/g, respectively, whereas the cells grown on native CNF substrate formed aggregates due to poor cell attachment and exhibited limited cell proliferation. In addition, the P-CNF substrates with optimal phosphate content provided a favorable cellular microenvironment and significantly promoted osteogenic differentiation and calcification, even in the absence of a differentiation inducer. The bio-based P-CNFs are expected to mimic the bone components and provide a means to regulate osteoblast proliferation and differentiation in bone tissue engineering.

Physicochemical and in vitro investigation of trace element-incorporated hydroxyapatite and starPCL@chitosan composite scaffold for bone tissue engineering

Organic-inorganic composite scaffolds are of interest for bone tissue engineering and post injury-bone regeneration. In the present study, aimed to investigate the suitability of the trace element-incorporated hydroxyapatite (THA) integrated bioactive gel (BioGel) (star-shaped polycaprolactone (starPCL)/Chitosan (Chit)) (THAiBioGel) composite scaffold which was fabricated using melt/solution blending method as a bone scaffold. The results revealed that the as-prepared THAiBioGel demonstrated that THA was successfully incorporated into BioGel and yield a desirable porous structure with mechanical strength of 10.35 ± 0.27 MPa, 13.62 ± 0.32 MPa and 18.30 ± 0.54 MPa for weight ratio of THA:BioGel 5:5, 7:3 and 9:1, respectively. Furthermore, the in vitro biological assay confirmed that the present material was not only good for osteoblast-like UMR-106 cell attachment on its surface, but also significantly promoted bone formation as demonstrated by an increase in alkaline phosphatase (ALP) activity. Our data, therefore, strongly suggested that THAiBioGel could be used as scaffold for bone tissue engineering.