Scaffolds For Bone Tissue Regeneration Research Articles

Hydroxyapatite reinforced natural polymer scaffold for bone tissue regeneration

Abstract Medical Advances had led to an increase in life expectancy. However one of the challenges confronted by the orthopaedic surgeon is the repair and restoration of skeletal bone defects resulting from trauma. Nano Hydroxyapatite combined with natural polymer starch can be used as a biomaterial for making scaffolds for the bone tissue regeneration process. This is used to improve the biocompatibility of the scaffolds for living cells. The materials are synthesized by Wet Chemical Method in liquid phase, dried to obtain solid particles and solvent casting technique is used for making the scaffolds in the ratio 1:1. Cytotoxicity test revealed that obtained scaffold materials are highly compatible and non-toxic to the body.

Succinylated Bacterial Cellulose Induce Carbonated Hydroxyapatite Deposition in a Solution Mimicking Body Fluid

Incorporation of bone-like hydroxyapatite into bacterial cellulose (BC) is an attractive approach for the fabrication of a bioactive three-dimensional (3D) scaffold for bone tissue regeneration. This study investigates the influence of the succinylation of BC on its ability to incorporate bone-like hydroxyapatite. A biomimetic process using a 1.5 × Simulated Body Fluid (SBF) was used to deposit the hydroxyapatite into the succinylated-BC. After soaking the succinylated-BC in the 1.5 × SBF for six days, Scanning Electron Microscope (SEM) images were taken and the composition of the succinylated-BC was analyzed by energy dispersive X-ray spectrometry. The biocompatibility of the scaffolds was tested in vitro using rat Bone Marrow Stromal Cells (rBMSCs). The SEM images and Fourier Transform Infrared Spectroscopy (FTIR) spectra showed that carbonated hydroxyapatite was deposited on the succinylated-BC. In contrast, only a small amount of carbonated hydroxyapatite deposition was observed on unmodified BC, indicating that the succinyl group in the BC is effective for inducing hydroxyapatite deposition. In vitro studies using rBMSCs revealed the biocompatibility of the scaffold. Combining with the ability of the cells to differentiate into bone cells, the succinylated-BC scaffold is a promising 3D scaffold for bone tissue regeneration.

Sandwich-Like Nanofibrous Scaffolds for Bone Tissue Regeneration.

Advanced bone healing approaches included a wide range of biomaterials that mainly mimic the composition, structure, and properties of bone extracellular matrix with osteogenic activity. The present study aimed to develop a sandwich-like structure of electrospun nanofibers (NFs) based on polycaprolactone (PCL) and chitosan/polyethylene oxide (CS/PEO) composite to stimulate bone fracture healing. The morphology of the fabricated scaffolds was examined using scanning electron microscopy (SEM). Apatite deposition was evaluated using simulated body fluid (SBF). The physicochemical and mechanical properties of samples were analyzed by Fourier transform infrared, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and universal testing machine. SEM images exhibited a porous three-dimensional structure with NF diameters of 514-4745 nm and 68-786 nm for PCL NFs layer and the sandwich-like NFs scaffolds, respectively. Deposition of apatite crystal on scaffolds started at week 2 followed by heavy deposition at week 8. This was confirmed by measuring the consumption of calcium and phosphorous ions from SBF. Thermal stability of scaffolds was confirmed using DSC and TGA. Moreover, the PCL NF layer in the middle of the developed sandwich structure reinforced the scaffolds with bear load up to 12.224 ± 1.12 MPa and Young's modulus of 17.53 ± 3.24 MPa. The scaffolds' porous structure enhanced both cell propagation and proliferation. Besides, the presence of CS in the outer NF layers of the scaffolds increased the hydrophilicity, as evidenced by the reduction of contact angle from 116.6 to 57.6°, which is essential for cell attachment. Cell viability study on mesenchymal stem cells proved the cytocompatibility of the fabricated scaffolds. Finally, in vivo mandibular bone defect rabbit model was used to confirm the regeneration of a new healthy bone within 28 days. In conclusion, the developed scaffolds could be a promising solution to stimulate bone regeneration.

The effect of chelation of sodium alginate with osteogenic ions, calcium, zinc, and strontium.

Alginates are attractive in tissue regeneration due to their similarity to the extracellular matrix, biocompatibility, biodegradability, non-antigenicity, and the ability to undergo ionotropic gelation. Alginate hydrogels are formed by ionic crosslinking mainly using calcium ions with some reports on the use of strontium and zinc ions. Strontium and zinc ions in trace amounts are known to accelerate bone healing due to their role in regulating osteoblasts and osteoclasts in addition to their antibacterial properties. This study reports the effect of forming alginate hydrogel films using three different ionic species, Ca2+, Zn2+ and Sr2+ with different M/G ratios on their physical properties as a method of introducing these ions in alginate composites for bone tissue engineering. The results reveal that mechanical and thermal properties of alginate films along with their water sorption behaviour are affected by the type of ions that crosslink them and the relative amounts of M and G length of the different block structures influence the gel forming ability. Since calcium, zinc and strontium are ions of interest due to their osteogenic properties, the results of this study can be used to tailor the properties of alginates for the development of composite scaffolds for bone tissue regeneration.

Titanium - castor oil based polyurethane composite foams for bone tissue engineering

Polyurethanes (PU) foams with titanium particles (Ti) were prepared with castor oil (CO) and isophorone diisocyanate (IPDI) as polymeric matrix, and 1, 3 and 5 wt.% of Ti. Composites were physicochemically and mechanically characterized and their biocompatibility assessed using human dental pulp stem cells (HDPSC). PU synthesis was confirmed by FTIR, but the presence of Ti was detected by RAMAN, X-ray diffraction (peak at 2θ = 40.2°) and by EDX-mapping. Materials showed three decomposition temperatures between 300 °C and 500 °C and their decomposition were not catalyzed by Ti particles. Compressive modulus (164–846 kPa), compressive strength (12.9–116.7 kPa) and density (128–240 kg/m3) tend to increase with Ti concentration but porosity was reduced (87% to 80%). Composites’ foams were fully degraded in acid and oxidative media while remained stable in distilled water. HDPSC viability on all composites was higher than 80% up to 14 days while proliferation dropped up to 60% at 21 days. Overall, these results suggest that these foams can be used as scaffolds for bone tissue regeneration.

Phenytoin/sildenafil loaded poly(lactic acid) bilayer nanofibrous scaffolds for efficient orthopedics regeneration

Autologous and synthetic bone grafts showed some limitations during their usage in bone tissue regeneration. This is attributed to several drawbacks such as difficulty of finding a donor in addition to the autoimmune rejection. This study aims to fabricate a well-designed biocompatible double-layered structure of highly porous poly(lactic acid)-based electrospun nanofibers (NFs) as scaffolds for bone tissue regeneration. Poly(lactic acid) was chosen to fabricate the main matrix of the NFs scaffold as it is one of the FDA approved and highly recommended biopolymers for biomedical applications owing to its high biodegradability and biocompatibility Each layer is loaded with a different drug (Phenytoin and Sildenafil) to stimulate bone healing process. The solvents and the parameters of electrospinning were manipulated to produce highly porous structures in order to enhance the in-situ biodegradability of the NFs mats as well as the drug release rate. The produced NFs mats were fully characterized morphologically (SEM), chemically (FTIR), physically (DSC) and physicochemically (biodegradability, swellability, porosity and water vapor permeability) as well as studying the drug release profiles of both drugs. Cytotoxicity of the fabricated NFs was tested using fibroblast cells to detect their biocompatibility. Cell adhesion and proliferation were examined using SEM before using the NFs as scaffolds in mice animal model. The efficiency of the developed NFs scaffolds in healing bone fractures was assessed after 14 and 28 days through visual inspection, SEM investigation and bone mineral density assessment. Finally, sections from the bone fracture sites were isolated for histopathological examination. The study revealed the efficiency of the drugs-loaded NFs in enhancing cell adherence, cell proliferation, angiogenesis formation and finally tissue restoration of bone fractures.

Proliferation and osteogenic differentiation of human mesenchymal stem cells in PCL/silanated silica composite scaffolds for bone tissue regeneration

Here, we fabricated composite scaffolds consisting of poly ε-caprolactone (PCL) and silanated silica particles and evaluated the performance of these composite scaffolds as suitable alternatives for bone tissue regeneration including their physical properties (tensile modulus, wettability, and surface roughness) and biological properties (cell proliferation, osteogenic differentiation, Q-PCR, western blotting, and migration assay), by culturing human mesenchymal stem cells. PCL/silanated silica scaffolds had outstanding physical characteristics and biological properties including cell proliferation, osteogenic differentiation, and osteoinduction. This silanated-silica composite has a strong potential as a biomaterial and can be applied to bone tissue applications.

Three-dimensional gelatin/PVA scaffold with nanofibrillated collagen surface for applications in hard-tissue regeneration

The surface topography of a tissue-engineered scaffold is widely known to play an essential role in bone tissue engineering applications. Therefore, the cell-to-material interaction should be considered when developing scaffolds for bone tissue regeneration. Bone is a dynamic tissue with a distinct hierarchical structure composed of mostly collagen and bioceramics. In this study, the surface of gelatin/PVA scaffold (CF-G5P5) coated with fibrillated collagen was fabricated to enhance cell proliferation and osteogenic differentiation for bone tissue regeneration. The physical and biological properties of the fabricated scaffolds were investigated. As a result, the CF-G5P5 scaffold increased surface roughness and increased protein absorption compared to a gelatin/PVA scaffold (G5P5) by 1.6 times from OD value 0.43 to 0.71 after 12 h, cell proliferation increased 1.7 times from OD value 0.57 to 0.96, and differentiation increased by 1.5 times from 100 to 151%. Based on the results, the CF-G5P5 scaffold developed can be considered as a highly potential bone tissue regenerative material.

Fabrication of hierarchically porous silk fibroin-bioactive glass composite scaffold via indirect 3D printing: Effect of particle size on physico-mechanical properties and in vitro cellular behavior

In order to regenerate bone defects, bioactive hierarchically scaffolds play a key role due to their multilevel porous structure, high surface area, enhanced nutrient transport and diffusion. In this study, novel hierarchically porous silk fibroin (SF) and silk fibroin-bioactive glass (SF-BG) composite were fabricated with controlled architecture and interconnected structure, by combining indirect three-dimensional (3D) inkjet printing and freeze-drying methods. Further, the effect of 45S5 Bioactive glass particles of different sizes (<100 nm and 6 μm) on mechanical strength and cell behavior was investigated. The results demonstrated that the hierarchical structure in this scaffold was composed of two levels of pores in the order of 500–600 μm and 10–50 μm. The prepared SF-BG composite scaffolds utilized by nano and micro particles possessed mechanical properties with a compressive strength of 0.94 and 1.2 MPa, respectively, in dry conditions. In a wet condition, the hierarchically porous scaffolds did not exhibit any fluctuation after compression load cell and were incredibly flexible, with excellent mechanical stability. The SF-BG composite scaffold with nanoparticles presented a significant 50% increase in attachment of human bone marrow stem cells in comparison with SF and SF-BG scaffold with microparticles. Moreover, SF-BG scaffolds promoted alkaline phosphatase activity as compared to SF scaffolds without BG particles on day 14. In brief, the 3D porous silk fibroin-based composites containing BG nanoparticles with excellent mechanical properties are promising scaffolds for bone tissue regeneration in high load-bearing applications.

Engineered bio-nanocomposite magnesium scaffold for bone tissue regeneration

Porous magnesium based materials are gaining intensive potential as a substitute scaffold material in the field of biomedical engineering as their mechanical properties such as compressive strength and elastic modulus are quite similar to that of human bone. Considering the poor mechanical integrity of ceramic and polymeric materials, metallic implants such as magnesium based alloy foams can be used as a promising scaffold material for bone tissue engineering. Magnesium foams also have properties like excellent biocompatibility and biodegradability so that revision surgery can be completely eliminated after implantation in orthopaedic applications. Against this background, porous Mg alloy based bioactive nano-composite foams were developed. Nano-hydroxyapatite (n-HA) was used as bioactive reinforcement which was anticipated to enhance bone tissue regenerations. Magnesium based alloy compositions were developed by incorporating selective alloying elements, while the bioactive nano-composite foams were fabricated using powder metallurgy route. The powder metallurgy route involved sequential stages of mixing and compaction of all powders with carbamide powder as a space holding material, followed by sintering of the green compacts. The microstructures of these nano-ceramic reinforced metal matrix foams were studied by scanning electron microscopy (SEM) in combination with energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD) and X-ray micro computed tomography (X-ray micro CT). Further, mechanical properties of the nanocomposite foams were evaluated. SEM and EDS results confirmed a homogeneous distribution of pores, alloying elements and n-HA. Structure–property correlations were established through the microstructural characterizations. The study therefore demonstrated that selected Mg alloy based composite foam can be an excellent candidate material for bone tissue engineering.

Mussel-inspired hybrid coating functionalized porous hydroxyapatite scaffolds for bone tissue regeneration

The scaffold for bone tissue engineering should possess proper porosity, adequate mechanical properties, cell affinity for cell attachment, and the capability to bind bioactive agents to induce cell differentiation. In this study, we successfully prepared a porous hydroxyapatite (HA) scaffold that is functionalized by poly(L-lysine)/polydopamine (PLL/PDA) hybrid coating. The PLL/PDA coating takes advantages of the high protein and cell affinity of PDA, as well as the biodegradability of PLL. Therefore, the coating can anchor bone morphogenic protein-2 (BMP2) to the HA scaffold via catechol chemistry under a mild condition so as to protect the bioactivity of BMP2. Meanwhile, the coating can also release BMP2 in a tunable and sustainable manner as the PLL degrades in the physiological environment. The BMP2-entrapped PLL/PDA coating on the HA scaffold can more efficiently promote osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro and induce ectopic bone formation to a much greater level in vivo compared with a bare HA scaffold that delivers BMP2 in a burst manner. All of these results suggest that the PDA-mediated catechol modification of the HA scaffold can be an effective strategy to develop sustainable protein delivery system, and that the PLL/PDA-coated HA scaffold could be a promising candidate for bone tissue engineering applications.

Injectable Alginate-Peptide Composite Hydrogel as a Scaffold for Bone Tissue Regeneration.

The high demand for tissue engineering scaffolds capable of inducing bone regeneration using minimally invasive techniques prompts the need for the development of new biomaterials. Herein, we investigate the ability of Alginate incorporated with the fluorenylmethoxycarbonyl-diphenylalanine (FmocFF) peptide composite hydrogel to serve as a potential biomaterial for bone regeneration. We demonstrate that the incorporation of the self-assembling peptide, FmocFF, in sodium alginate leads to the production of a rigid, yet injectable, hydrogel without the addition of cross-linking agents. Scanning electron microscopy reveals a nanofibrous structure which mimics the natural bone extracellular matrix. The formed composite hydrogel exhibits thixotropic behavior and a high storage modulus of approximately 10 kPA, as observed in rheological measurements. The in vitro biocompatibility tests carried out with MC3T3-E1 preosteoblast cells demonstrate good cell viability and adhesion to the hydrogel fibers. This composite scaffold can induce osteogenic differentiation and facilitate calcium mineralization, as shown by Alizarin red staining, alkaline phosphatase activity and RT-PCR analysis. The high biocompatibility, excellent mechanical properties and similarity to the native extracellular matrix suggest the utilization of this hydrogel as a temporary three-dimensional cellular microenvironment promoting bone regeneration.

Highly porous PHB-based bioactive scaffolds for bone tissue engineering by in situ synthesis of hydroxyapatite

In this study bioactive and bioresorbable porous scaffolds for bone tissue regeneration, based on poly(3-hydroxybutyrate) (PHB), are presented. The porous structure is obtained by thermally induced phase separation (TIPS) technique, whereas the osteoinductivity and osteoconductivity are enhanced through the incorporation of hydroxyapatite (HA). The HA particles are generated in PHB using an innovative filler in situ synthesis, and the properties of the composite scaffolds are then compared to scaffolds obtained by conventional mechanical dispersion of ex situ synthesized HA particles. The in situ synthesis leads to composite materials with improved porosity, even at high filler content, without any degradation of the polymeric matrix as confirmed by GPC and DSC measurements. On the contrary, the samples prepared by ex situ method show a suppressed porosity by increasing the inorganic filler content, therefore limiting the amount of HA that can be loaded in PHB and the resulting bioactivity. The possibility to use PHB/HA porous composites as scaffolds for bone tissue regeneration, is assessed by preliminary cell viability in vitro studies. In particular, it is observed that the composites are fully cytocompatible and able to sustain MC3T3-E1 mouse pre-osteoblast cells adhesion and proliferation. Investigations on cell morphology reveal, for all PHB/HA scaffolds, the presence of differentiated cells with a predominance of osteocyte-like morphology, which are not observed for neat PHB scaffolds. Moreover, the MC3T3-E1 cells differentiation towards osteoblastic phenotype is further supported by the evaluation of the early osteogenic markers. In particular, samples loaded with HA in situ synthesized showed the highest ALP production and typical morphology of the terminal differentiation stages of osteoblasts.

Green reduced graphene oxide functionalized 3D printed scaffolds for bone tissue regeneration

The incorporation of reduced graphene oxide (rGO) nanomaterials into scaffolds structure can be explored to enhance the properties of these 3D matrices in bone regeneration applications. However, the weak water solubility and poor colloidal stability of rGO have hindered its incorporation in blends aimed to produce scaffolds by 3D printing. Furthermore, rGO is generally obtained by treating graphene oxide (GO) with hydrazine hydrate, which is a highly hazardous reducing agent. To overcome these problems, herein a novel environmentally-friendly method was developed to assemble 3D printed scaffolds incorporating rGO. Such was achieved through the in situ reduction mediated by l-Ascorbic acid of the GO already present on tricalcium phosphate/gelatin/chitosan scaffolds. The scaffolds functionalized with rGO through the in situ method (TGC_irGO) displayed enhanced wettability and improved mechanical properties without impairing their porosity when compared to their equivalents functionalized with GO and non-functionalized scaffolds (TGC_GO and TGC, respectively). Moreover, the TGC_irGO scaffolds displayed an improved calcium deposition at their surface and an enhanced alkaline phosphatase (ALP) activity, along 21 days of incubation. Additionally, scaffolds also displayed antimicrobial activity without compromising osteoblasts’ viability and proliferation. Such features reveal the potential of the TGC_irGO scaffolds for bone tissue regeneration applications.

Load-bearing biodegradable polycaprolactone-poly (lactic-co-glycolic acid)- beta tri-calcium phosphate scaffolds for bone tissue regeneration.

A biodegradable scaffold with tissue ingrowth and load-bearing capabilities is required to accelerate the healing of bone defects. However, it is difficult to maintain the mechanical properties as well as biodegradability and porosity (necessary for bone ingrowth) at the same time. Therefore, in the present study, polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA5050) were mixed in varying ratio and incorporated with 20 wt.% βTCP. The mixture was shaped under pressure into originally non-porous cylindrical constructs. It is envisioned that the fabricated constructs will develop porosity with the time-dependent biodegradation of the polymer blend. The mechanical properties will be sustained since the decrease in mechanical properties associated with the dissolution of the PLGA and the formation of the porous structure will be compensated with the new bone formation and ingrowth. To prove the hypothesis, we have systematically studied the effects of samples composition on the time-dependent dissolution behavior, pore formation, and mechanical properties of the engineered samples, in vitro. The highest initial (of as-prepared samples) values of the yield strength (0.021±0.002 GPa) and the Young's modulus (0.829±0.096 GPa) were exhibited by the samples containing 75 wt.% of PLGA. Increase of the PLGA concentration from 25 wt.% to 75 wt.% increased the rate of biodegradation by a factor of 3 upon 2 weeks in phosphate buffered saline (1× PBS). The overall porosity and the pore sizes increased with the dissolution time indicating that the formation of in-situ pores can indeed enable the migration of cells followed by vascularization and bone growth.

The Application of Multi-Walled Carbon Nanotubes in Bone Tissue Repair Hybrid Scaffolds and the Effect on Cell Growth In Vitro.

In this study, composite scaffolds with different multi-walled carbon nanotubes (MWCNTs) content were prepared by freeze-drying. These scaffolds were characterized by scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), porosity, hydrophilicity, mechanical strength, and degradation. The MWCNTs scaffolds were structurally sound and had porous structures that offered ample space for adherence, proliferation, and differentiation of MC3T3-E1 cells, and also supported the transport of nutrients and metabolic waste. CS/Gel/nHAp/0.3%MWCNTs scaffolds provided the best outcomes in terms of scaffold porosity, hydrophilicity, and degradation rate. However, CS/Gel/nHAp/0.6%MWCNTs scaffolds were found to support the optimal growth, homogenous distribution, and biological activity of MC3T3-E1 cells. The excellent properties of CS/Gel/nHAp/0.6%MWCNTs scaffolds for the adhesion, proliferation, and osteogenesis differentiation of MC3T3-E1 cells in vitro highlights the potential applications of this scaffold in bone tissue regeneration.

MODELLING OF BONE FIXATION PLATE FROM BIODEGRADABLE MAGNESIUM ALLOY / KAULŲ LŪŽIŲ FIKSAVIMO PLOKŠTELIŲ IŠ BIODEGRADUOJANČIO MAGNIO LYDINIO MODELIAVIMAS

Biodegradable materials are used in two key sectors of orthopaedics – to fabricate bone fixators and scaffolds for bone tissue regeneration. In case of osteosynthesis, fixators made from biodegradable materials disappear from the body after a certain time. So, a necessity of a one more operation for their removal is excluded. In the present study, the acromioclavicular joint osteosynthesis plates made of magnesium alloy (WE43), titanium alloy (Ti-6Al-7Nb) and stainless steel (316L) are compared utilizing the finite element analysis. The research showed that stresses in the magnesium alloy plate were lower, compared to the titanium alloy plate or the stainless steel plate. However, the tensile strength of magnesium is over 2 times lower, as compared to stainless steel and 5 times lower, than titanium alloys. Magnesium alloy is not suitable for manufacturing plates with low thickness (2 and 2.5 mm), because the stresses generated in them exceed the yield strength of the material.

3D Printed Polymer Scaffolds for Bone Tissue Regeneration

The regeneration of bone defects is a significant clinical challenge for patients around the world. The ideal scaffolds for bone tissue repair should provide biocompatibility, pore architecture, biodegradability, mechanical support, and cell attachment sites. Conventionally fabricated polymer scaffolds are still unable to make ideal scaffolds for bone tissue repair due to the lack of all the above mentioned properties. The investigated hypothesis was that increasing pore sizes of the scaffolds would cause an increase in the porosity and a decrease in the compressive modulus. In order to test the hypothesis, we designed three different pore sizes (200, 400, and 800 μm) in three different scaffolds using computer software. Relatively new 3D printing technology was used to print the three different types of porous scaffolds using polycaprolactone (PCL) polymer. These scaffolds were characterized for percent porosity, pore architecture, morphology, mechanical properties, and evaluated for biocompatibility and cell attachment with murine pre-osteoblasts. The percent porosity of these scaffolds (n=7) significantly increased from 13.31 to 61.66 (p&amp;lt;0.001) with the increase in pore size. The average compressive modulus of scaffolds (n=7) significantly decreased with the increase in pore size (p&amp;lt;0.001). The averaged compressive modulus of scaffolds with 200, 400, and 800 μm pores is 82.98 ± 2.02, 61.60 ± 2.59, and 47.16 ± 1.73 MPa, respectively. In addition, PCL scaffolds show biocompatibility as determined by an in vitro cell study. These results have shown that the hypothesis is validated, and these 3D printed porous PCL scaffolds can be potentially used for bone regeneration applications.

Fabrication and characterization of the 3D-printed polycaprolactone/fish bone extract scaffolds for bone tissue regeneration.

Fish bone extract (FBE) containing a trioligopeptide (FBP-KSA, Lys-Ser-Ala) isolated from Johnius belengerii could induce osteogenic activities on MC3T3-E1 pre-osteoblasts in our previous study. Regarding the osteogenic effect of FBE, in the present study, we fabricated the three-dimensional (3D) interconnected polycaprolactone (PCL)/FBE scaffolds for bone tissue regeneration. After fabrication of PCL scaffolds using 3D printing, FBE was coated on the surface of PCL scaffolds by self-assembly process. In the physical characteristic and mechanical property tests, the results demonstrated that the fabricated scaffolds have the strut diameter (between 340 and 345 μm), pore size (between 470 and 480 μm), porosity (between 50% and 55%), and tensile properties (Young's modulus: 9.18-9.42 MPa; max tensile strengths 82.3-87.4 MPa) were similar to those of PCL scaffold. In the cell proliferation and osteogenic assay, the results showed that PCL/FBE scaffolds could significantly induce cell proliferation, calcium deposition, and the expression of osteogenic phenotype markers such as alkaline phosphatase, osteopontin, osteocalcin, and bone morphogenetic protein-2 in the osteoblasts. These results suggest that FBE-coated PCL scaffolds are promising materials for use in biomedical application to promote bone tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1937-1944, 2019.

Surface functionalization of 3D printed polymer scaffolds to augment stem cell response

Three-dimensional (3D) printing by material extrusion is being widely explored to prepare patient-specific scaffolds from biodegradable polyesters such as poly(lactic acid) (PLA). Although they provide the desired mechanical support, PLA scaffolds lack bioactivity to promote bone regeneration. The aim of this work was to develop a surface engineering approach for enhancing the osteogenic activity of 3D printed PLA scaffolds. Macro-porous PLA scaffolds were prepared by material extrusion with 70.2% porosity. Polyethyleneimine was chemically conjugated to the alkali-treated PLA scaffolds followed by conjugation of citric acid. These polymer-grafted scaffolds were immersed in the simulated body fluid to yield scaffolds coated with calcium-deficient hydroxyapatite (PLA-HaP). Surface roughness and water wettability were enhanced after surface modification. PLA-HaP scaffolds exhibited a steady release of calcium ions in an aqueous medium for 10 days. The adhesion and proliferation of human mesenchymal stem cells (hMSCs) on PLA-HaP was ~50% higher than on PLA. Mineral deposition resulting from hMSC osteogenesis on PLA-HaP scaffolds was nearly twice that on PLA scaffolds. This was corroborated by the increase in alkaline phosphatase activity and expression of several osteogenic genes. Thus, this work presents a surface modification strategy to enhance the bioactivity of 3D printed scaffolds for bone tissue regeneration.