Scaffolds For Bone Tissue Engineering Research Articles

Investigations on effect of pore architectures of additively manufactured novel hydroxyapatite coated PLA/Al2O3 composite scaffold for bone tissue engineering

Purpose The purpose of this paper is to fabricate the scaffolds with different pore architectures using additive manufacturing and analyze its mechanical and biological properties for bone tissue engineering applications. Design/methodology/approach The polylactic acid (PLA)/composite filament were fabricated through single screw extrusion and scaffolds were printed with four different pore architectures, i.e. circle, square, triangle and parallelogram with fused deposition modelling. Afterwards, scaffolds were coated with hydroxyapatite (HA) using dip coating technique. Various physical and thermo-mechanical tests have been conducted to confirm the feasibility. Furthermore, the biological tests were conducted with MG63 fibroblast cell lines to investigate the biocompatibility of the developed scaffolds. Findings The scaffolds were successfully printed with different pore architectures. The pore size of the scaffolds was found to be nearly 1,500 µm, and porosity varied between 53% and 63%. The fabricated circular pore architecture resulted in highest average compression strength of 13.7 MPa and modulus of 525 MPa. The characterizations showed the fidelity of the work. After seven days of cell culture, it was observed that the developed composites were non-toxic and supported cellular activities. The coating of HA made the scaffolds bioactive, showing higher wettability, degradation and high cellular responses. Originality/value The research attempts highlight the development of novel biodegradable and biocompatible polymer (PLA)/bioactive ceramic (Al2O3) composite for additive manufacturing with application in the tissue engineering field.

Fabrication, characterization and biological properties evaluation of bioactive scaffold based on mineralized carbon nanofibers

Tissue engineering as an innovative approach aims to combine engineering, biomaterials and biomedicine to eliminate the drawbacks of conventional bone defect treatment. In the current study, we fabricated bioengineered electroactive and bioactive mineralized carbon nanofibers as the scaffold for bone tissue engineering applications. The scaffold was fabricated using the sol–gel method and thoroughly characterized by SEM imaging, EDX analysis and a 4-point probe. The results showed that the CNFs have a diameter of 200 ± 19 nm and electrical conductivity of 1.02 ± 0.12 S cm−1. The in vitro studies revealed that the synthesized CNFs were osteoactive and supported the mineral crystal deposition. The hemolysis study confirmed the hemocompatibility of the CNFs and cell viability/proliferation sassy using an MTT assay kit showed the proliferative activities of mineralized CNFs. In conclusion, this study revealed that the mineralized CNFs synthesized by the combination of sol–gel and electrospinning techniques were electroactive, osteoactive and biocompatible, which can be considered an effective bone tissue engineering scaffold. Communicated by Ramaswamy H. Sarma

Characteristic Evaluation of Recombinant MiSp/Poly(lactic-co-glycolic) Acid (PLGA) Nanofiber Scaffolds as Potential Scaffolds for Bone Tissue Engineering.

Biomaterial-based nanofibrous scaffolds are the most effective alternative to bone transplantation therapy. Here, two recombinant minor ampullate spidroins (spider silk proteins), R1SR2 and NR1SR2C, were blended with Poly(lactic-co-glycolic) Acid (PLGA), respectively, to generate nanofiber scaffolds by electrospinning. The N-terminal (N), C-terminal (C), repeating (R1 and R2) and spacer (S) modules were all derived from the minor ampullate spidroins (MiSp). The physical properties and structures of the blended scaffolds were measured by scanning electron microscopy (SEM), water contact angle measurement, Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), and Tensile mechanical testing. The results showed that blending of MiSp (R1SR2 and NR1SR2C) reduced the diameter of nanofibers, increased the porosity and glass transition temperatures of nanofibrous scaffolds, and effectively improved the hydrophilicity and ultimate strain of scaffolds. It is worth noting that the above changes were more significant in the presence of the N- and C-termini of MiSp. In cell culture assays, human bone mesenchymal stem cells (HBMSCs) grown on NR1SR2C/PLGA (20/80) scaffolds displayed markedly enhanced proliferative and adhesive abilities compared with counterparts grown on pure PLGA scaffolds. Jointly, these findings indicated recombinant MiSp/PLGA, particularly NR1SR2C/PLGA (20/80) blend nanofibrous scaffolds, is promising for bone tissue engineering.

3D printing method for bone tissue engineering scaffold

3D printing technology is an emerging technology. It constructs solid bodies by stacking materials layer by layer, and can quickly and accurately prepare bone tissue engineering scaffolds with specific shapes and structures to meet the needs of different patients. The field of life sciences has received a great deal of attention. However, different 3D printing technologies and materials have their advantages and disadvantages, and there are limitations in clinical application. In this paper, the technology, materials and clinical applications of 3D printed bone tissue engineering scaffolds are reviewed, and the future development trends and challenges in this field are prospected.

Osteogenic potential of a 3D printed silver nanoparticle-based electroactive scaffold for bone tissue engineering using human Wharton's jelly mesenchymal stem cells

This study aims to perform biological assessments of an electroactive scaffold based on PCL/AgNPs that was fabricated using a green synthesis approach followed by a 3D printing method without toxic solvents, which has not been explored previously.

Tubular nanomaterials for bone tissue engineering.

Nanomaterial composition, morphology, and mechanical performance are critical parameters for tissue engineering. Within this rapidly expanding space, tubular nanomaterials (TNs), including carbon nanotubes (CNTs), titanium oxide nanotubes (TNTs), halloysite nanotubes (HNTs), silica nanotubes (SiNTs), and hydroxyapatite nanotubes (HANTs) have shown significant potential across a broad range of applications due to their high surface area, versatile surface chemistry, well-defined mechanical properties, excellent biocompatibility, and monodispersity. These include drug delivery vectors, imaging contrast agents, and scaffolds for bone tissue engineering. This review is centered on the recent developments in TN-based biomaterials for structural tissue engineering, with a strong focus on bone tissue regeneration. It includes a detailed literature review on TN-based orthopedic coatings for metallic implants and composite scaffolds to enhance in vivo bone regeneration.

Deep eutectic solvent-assisted fabrication of bioinspired 3D carbon-calcium phosphate scaffolds for bone tissue engineering.

Tissue engineering is a burgeoning field focused on repairing damaged tissues through the combination of bodily cells with highly porous scaffold biomaterials, which serve as templates for tissue regeneration, thus facilitating the growth of new tissue. Carbon materials, constituting an emerging class of superior materials, are currently experiencing remarkable scientific and technological advancements. Consequently, the development of novel 3D carbon-based composite materials has become significant for biomedicine. There is an urgent need for the development of hybrids that will combine the unique bioactivity of ceramics with the performance of carbonaceous materials. Considering these requirements, herein, we propose a straightforward method of producing a 3D carbon-based scaffold that resembles the structural features of spongin, even on the nanometric level of their hierarchical organization. The modification of spongin with calcium phosphate was achieved in a deep eutectic solvent (choline chloride : urea, 1 : 2). The holistic characterization of the scaffolds confirms their remarkable structural features (i.e., porosity, connectivity), along with the biocompatibility of α-tricalcium phosphate (α-TCP), rendering them a promising candidate for stem cell-based tissue-engineering. Culturing human bone marrow mesenchymal stem cells (hMSC) on the surface of the biomimetic scaffold further verifies its growth-facilitating properties, promoting the differentiation of these cells in the osteogenesis direction. ALP activity was significantly higher in osteogenic medium compared to proliferation, indicating the differentiation of hMSC towards osteoblasts. However, no significant difference between C and C-αTCP in the same medium type was observed.

Aloe-vera-based biopolymeric composite scaffolds for bone tissue engineering: A review

From, ancient times, aloe-vera (AV) has been identified as an extraordinary traditional medicinal and pharmaceutical biomaterial herb. Many reports suggest that it has many biologically active components. Its bioactive compound has a well-established spectrum of effective anti-inflammatory, antibacterial, antioxidant, biocompatible, biodegradable, anti-diabetic, and antimicrobial properties. To get different types of desired properties like mechanical stability (compression, tensile strength, toughness, etc.), and biocompatibility, different naturally available materials (alginate, collagen, chitosan, etc.) and synthetic biopolymers (PLA, PLGA, PCL, etc.) with aloe-vera (AV) are used to synthesis biocomposites for bone scaffold. Different ceramics materials such as hydroxyapatite (Hap), calcium phosphates, B-tricalcium phosphate (b-TCP), etc. are utilized for bone implants along with naturally available materials to incorporate bioactivity which enhances bone tissue regeneration. Nowadays, aloe-vera (AV) based biopolymer composites have obtained a lot of interest in bone tissue engineering (BTE) due to their biological and physicochemical properties. There are multiple types of bone scaffold fabrication techniques, like 3D printing techniques (Fused Deposition Modelling (FDM)), electrospinning techniques, etc., used in bone tissue engineering. This review outlines the current status of aloe-vera (AV) with biopolymer-based composites and their applications in bone tissue engineering (BTE).

Concentric-mineralized hybrid silk-based scaffolds for bone tissue engineering in vitro models.

There are many challenges in the development of 3D-tissue models for studying bone physiology and disease. Silk fibroin (SF), a natural fibrous protein used in biomedical applications has been studied for bone tissue engineering (TE) due to its mechanical properties, biocompatibility and biodegradability. However, low osteogenic capacity as well as the necessity to reinforce the protein mechanically for some orthopedic applications prompts the need for further designs for SF-based materials for TE bone. Concentric mineralized porous SF-based scaffolds were developed to improve mechanics and mineralization towards osteoregeneration. Hybrid SF silica microparticles (MP) or calcium carbonate nano-structured microparticles (NMP) were seeded with hMSCs co-cultured under osteogenic and osteoclastic conditions with THP-1 human monocytes up to 10 weeks to simulate and recapitulate bone regeneration. Scaffolds with appropriate pore size for cell infiltration, resulted in improved compressive strength, increased cell attachment and higher levels of expression of osteogenic markers and mineralization after adding the NMPs, compared to controls systems without these particles. These hybrid SF-based 3D-structures can provide improved scaffold designs for in vitro bone TE.

3D Printing Silk Fibroin/Hydroxyapatite/Sodium Alginate Composite Scaffolds for Bone Tissue Engineering

3D Printing Silk Fibroin/Hydroxyapatite/Sodium Alginate Composite Scaffolds for Bone Tissue Engineering

3D printing of PLA:CaP:GO scaffolds for bone tissue applications.

Graphene oxide (GO) has attracted increasing interest for biomedical applications owing to its outstanding properties such as high specific surface area, ability to bind functional molecules for therapeutic purposes and solubility, together with mechanical resistance and good thermal conductivity. The combination of GO with other biomaterials, such as calcium phosphate (CaP) and biodegradable polymers, presents a promising strategy for bone tissue engineering. Presently, the development of these advanced biomaterials benefits from the use of additive manufacturing techniques, such as 3D printing. In this study, we develop a 3D printed PLA:CaP:GO scaffold for bone tissue engineering. First, GO was characterised alone by XPS to determine its main bond contributions and C : O ratio. Secondly, we determined the GO dose which ensures the absence of toxicity, directly exposed in vitro (human osteoblast-like cells MG-63) and in vivo (zebrafish model). In addition, GO was microinjected in the zebrafish to evaluate its effect on immune cells, quantifying the genetic expression of the main markers. Results indicated that the GO tested (C : O of 2.14, 49.50% oxidised, main bonds: C-OH, C-O-C) in a dose ≤0.25 mg mL-1 promoted MG63 cells viability percentages above 70%, and in a dose ≤0.10 mg mL-1 resulted in the absence of toxicity in zebrafish embryos. The immune response evaluation reinforced this result. Finally, the optimised GO dose (0.10 mg mL-1) was combined with polylactic acid (PLA) and CaP to obtain a 3D printed PLA:CaP:GO scaffold. Physicochemical characterisation (SEM/EDS, XRD, FT-Raman, nano-indentation) was performed and in vivo tests confirmed its biocompatibility, enabling a novel approach for bone tissue-related applications.

Akermanite Scaffolds for Bone Tissue Engineering: 3D Printing Using Polymer Precursor and Scaffold Properties

Akermanite Scaffolds for Bone Tissue Engineering: 3D Printing Using Polymer Precursor and Scaffold Properties

Application of silk fibroin composite scaffold in bone tissue engineering

As a natural protein, silk protein has superior biocompatibility, biodegradability and mechanical properties, and can be used in different forms for bone tissue repair in bone tissue engineering as a good biomaterial. The treatment of bone defect has always been a serious challenge for orthopedic surgeons. However, the traditional treatment of bone defect is autologous bone and bone allograft, with limited source and secondary injury with sampling site; the allograft faces ethical problems, rejection, and viral transmission risk. Tissue engineering is an important means to solve tissue and organ defects. It establishes a three-dimensional space complex composed of cells and biological materials and fills the defects, so as to repair the effect Bone tissue scaffold with filim protein plays a huge role in orthopedics, and is expected to bring good news to more patients with bone diseases in the future. In this paper, we review the structural characteristics, biological properties and applications of filamentous proteins in bone tissue engineering.

Critical Overview on Pure Chitosan-based Scaffolds for Bone Tissue Engineering: Clinical insights in Dentistry.

Bone Tissue Engineering (BTE) is a field of regenerative medicine continuously improving, thanks to the development of new biomaterials used as grafts or scaffolds for repairing bone defects. In recent years, chitosan, a natural biopolymer extracted mainly from crustacean shells, has demonstrated unique and desirable characteristics for BTE applications, such as: biocompatibility, biodegradability, and osteoconductive behavior. Additionally, the presence of numerous active amine groups in its chemical structure allows it to be easily modified. Data suggest that chitosan scaffolds are highly biomimetic, and show an interesting bioactivity, and antibacterial behavior. We have demonstrated, in a critical overview, how chitosan-based scaffolds may hold great interest for BTE applications in medical and dental applications. Future research should be focused on the use of chitosan-scaffolds combined with other biomaterials or bioactive molecules, to increase their overall regenerative potential, also in critical-sized defects. In conclusion, chitosan can be considered a promising biomaterial in BTE and clinical dentistry.

Nanoceramics-reinforced chitosan scaffolds in bone tissue engineering

An overview of nanobioceramics-reinforced chitosan combined with cells and growth factors for bone tissue engineering applications.

Optimized Method of 3D Scaffold Seeding, Cell Cultivation, and Monitoring Cell Status for Bone Tissue Engineering.

The cultivation of cells in 3D systems is commonly regarded to be more physiological than in 2D as it comes much closer to the natural situation in tissues in many different aspects. However, 3D cell culture is much more complex. Cells within the pores of a printed 3D scaffold face a special situation concerning cell-material interaction and cell adhesion, cell proliferation, and supply of medium and oxygen into the core of the scaffolds. Biological assays (for cell proliferation, viability, and activity) have been validated primarily for 2D cell cultures and need to be adapted for 3D cultures. Likewise, in imaging, a number of points need to be taken into account in order to get a clear picture of the cells in 3D scaffolds, preferably with the method of multiphoton microscopy. Here, we describe a method for pretreatment and cell seeding of porous inorganic composite scaffolds (α-TCP/HA) for bone tissue engineering and for cultivation of the cell-scaffold constructs. The analytical methods described are the cell proliferation assay and the ALP activity assay. A step-by-step protocol is provided here that safely tackles typical difficulties that arise with this 3D cell-scaffold setting. In addition, MPM imaging of cells is described both with and without labeling. The combination of biochemical assays and imaging provides valuable insights into the possibilities of analysis with this 3D cell-scaffold system.

Processing of gelatine coated composite scaffolds based on magnesium and strontium doped hydroxyapatite and yttria-stabilized zirconium oxide

Limited bone bank capacity and risk of infection are some of the main drawbacks of autologous and allogenic grafts, giving rise to synthetic materials for bone tissue implants. The aim of this study was to process and evaluate the mechanical properties and bioactivity of magnesium and strontium doped hydroxyapatite (HAp) scaffolds and investigate the effect of adding zirconium oxide and gelatine coating the scaffolds. Doped nanosized hydroxyapatite powder was synthesized by the hydrothermal method and the scaffolds were made by the foam replica technique and sintered at different temperatures. Yttria-stabilized zirconium oxide (YSZ), synthesized by plasma technology, was used as reinforcement of calcium phosphate scaffolds. Element analysis, phase composition, morphology of the powders and microstructure of the scaffolds were investigated, as well as the compressive strength of the coated and uncoated scaffolds and bioactivity in simulated body fluid (SBF). A microporous structure was achieved with interconnected pores and bioactivity in SBF was confirmed in all cases. The best mechanical properties were given by the coated composite HAp/YSZ scaffolds, withstanding average stresses of over 1019 kPa. These results encourage the idea of use of these scaffolds in bone regenerative therapy and bone tissue engineering.

Self-healing hydrogels for bone defect repair.

Severe bone defects can be caused by various factors, such as tumor resection, severe trauma, and infection. However, bone regeneration capacity is limited up to a critical-size defect, and further intervention is required. Currently, the most common clinical method to repair bone defects is bone grafting, where autografts are the "gold standard." However, the disadvantages of autografts, including inflammation, secondary trauma and chronic disease, limit their application. Bone tissue engineering (BTE) is an attractive strategy for repairing bone defects and has been widely researched. In particular, hydrogels with a three-dimensional network can be used as scaffolds for BTE owing to their hydrophilicity, biocompatibility, and large porosity. Self-healing hydrogels respond rapidly, autonomously, and repeatedly to induced damage and can maintain their original properties (i.e., mechanical properties, fluidity, and biocompatibility) following self-healing. This review focuses on self-healing hydrogels and their applications in bone defect repair. Moreover, we discussed the recent progress in this research field. Despite the significant existing research achievements, there are still challenges that need to be addressed to promote clinical research of self-healing hydrogels in bone defect repair and increase the market penetration.

Review on vat photopolymerization additive manufacturing of bioactive ceramic bone scaffolds.

Bone defects frequently occur in clinical settings due to trauma, disease, tumors, and other causes. The clinical use of autologous bones and allograft bone, however, has several limitations, such as limited sources, donor site morbidity, and immunological rejection. Nevertheless, there is newfound hope for regenerating and repairing bone defects through the development and integration of bone tissue engineering scaffold and additive manufacturing (AM) technology, also known as 3D printing. In particular, vat photopolymerization (VPP)-AM of bioactive ceramic bone scaffolds has garnered significant interest from interdisciplinary researchers in recent years. On the one hand, VPP-AM demonstrates clear advantages in printing accuracy and speed compared to other AM and non-AM technologies. On the other hand, bioactive ceramic materials exhibit superior bioactivity, biodegradability, and mechanical properties compared to metals, polymers, and bioinert ceramics, making them one of the most promising biomaterials for developing bone scaffolds. This paper reviews the research progress of VPP-AM of bioactive ceramic bone scaffolds, covering the process principles of various VPP-AM technologies, the performance requirements and preparation process of VPP ceramic slurry, the VPP process of bioactive ceramic bone scaffolds, and the research progress on different material types of VPP bioactive ceramic scaffolds. Firstly, we provide a brief introduction to the process principles and medical applications of various VPP technologies. Secondly, we explore the composition of the VPP ceramic slurry system, discussing the function of various components and their effects on printing quality. Thirdly, we delve into the performance requirements of bone scaffolds and summarize the research progress of VPP bioactive ceramic bone scaffolds of various material types including hydroxyapatite (HA), tricalcium phosphate (TCP), bioglass (BG), etc.; Finally, we discuss the challenges currently faced by VPP-AM bioactive ceramic bone scaffolds and propose possible development directions for the future.

Design and fabrication of biomimicking radially graded scaffolds via digital light processing 3D printing for bone regeneration.

Scaffolds are an essential component in bone tissue engineering (BTE). However, most of the current BTE scaffolds are homogeneous structures and do not resemble the graded architectures of native bone. In the current study, four types of biomimicking scaffold designs based on gyroid (G) and primitive (P) units with radially graded pore sizes were devised, and scaffolds of these designs with two porosity groups (65 vol% and 75 vol%) were fabricated via digital light processing (DLP) 3D printing using biphasic calcium phosphate (BCP). Scaffolds of the gyroid-gyroid (G-G) design displayed better dimensional accuracy, compressive property, and cell proliferation rate than gyroid-primitive (G-P), primitive-gyroid (P-G), and primitive-primitive (P-P) scaffolds. Subsequently, graded G-G scaffolds with different porosities were fabricated and the relationship between compressive strength and porosity was determined. Furthermore, the sintered BCP bioceramics fabricated via current manufacturing process exhibited excellent biocompatibility and bioactivity, indicating their high potential for BTE.