Scaffolds For Bone Tissue Regeneration Research Articles

Design of Biocompatible Chitosan/Polyaniline/Laponite Hydrogel with Photothermal Conversion Capability.

In recent years, multifunctional hydrogels have received a great deal of attention because they are biocompatible and can mimic the extracellular matrix. Herein, we prepared hydrogels of biocompatible cross-linked networks with photothermal properties. In this study, a chitosan/polyaniline/laponite (COL) hydrogel with photothermal conversion capability was designed. Polyaniline was firstly grafted onto chitosan and its solution was mixed with oxidized dextran, which was then cross-linked into a hydrogel via a Schiff base reaction. Furthermore, an aluminosilicate clay material, laponite (LAP), was incorporated into the hydrogel. The swelling ratio of the COL hydrogel in various solutions was greater than 580%, and it showed good degradation ability (the mass–loss ratio was over 45% after 28 days). This composite hydrogel was demonstrated to have good photothermal conversion properties and biocompatibility at both the cell (cell viability was over 97%) and animal levels. The COL hydrogel showed a photothermal conversion efficiency of 23.7% under the irradiation of a near-infrared laser. Coupled with the osteogenic differentiation-inducing potential of LAP, the COL hydrogel has the potential to kill tumors via hyperthermia or serve as scaffolds for bone tissue regeneration.

Coating of 3D printed PCL/TCP scaffolds using homogenized-fibrillated collagen

BackgroundPoly(3-caprolactone) (PCL)/β-tricalcium phosphate (β-TCP) composite scaffolds fabricated by three-dimensional (3D) printing are one of the common scaffolds for bone tissue regeneration. However, the main challenge of these 3D printed PCL/β-TCP scaffolds is the fact that many cells pass from porosities during in vitro cell seeding, leading to poor initial cell attachment. This study aimed to demonstrate the fabrication of a new collagen coating process for optimizing the hydrophilic property and cell-substrate interactions. This method may be used for coating collagen on any relevant biomedical constructs made of synthetic polymers to increase their biocompatibility and cell attachment. Materials and methodsPorous composite scaffolds fabricated by 3D printing were coated with collagen by a novel method and compared to traditional methods. After plasma treatment, samples were inverted in a homogenized collagen solution, freeze-dried, stabilized by crosslinking, freeze-dried again, and fibrillated using a defined salt concentration. Samples were characterized by a 3D laser microscope, cytocompatibility assay, attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy, water absorption, protein absorption, and bioactivity assay. ResultsHomogenized collagen at pH= 7 resulted in a very uniform layer on the surface of scaffolds with significantly higher cell proliferation (p < 0.05). Collagen-coated scaffolds showed significantly higher water absorption, protein absorption, and bioactivity compared to non-coated samples (p < 0.05). ConclusionThe results demonstrate that both the pH and collagen structure influence the coating of scaffolds, while the concentrations used in this study do not have a significant difference in this aspect. The combination of homogenization and fibrillization makes scaffolds more biocompatible and desirable for bone tissue engineering.

Efficacy of glycoprotein-based nanocurcumin/silk fibroin electrospun scaffolds: Perspective for bone apatite formation

In this research, a blend of poly (vinyl) alcohol (PVA), silk fibroin nanofibers (SF-NFs), hydroxyapatite nanoparticles (HA-NPs), and curcumin nanoparticles (Cu-NPs) were used to design a nanofibrous scaffold (NFS), by electrospun method, for their possible application in bone apatite formation. The prepared nanofibrous scaffold (NFS) was investigated using physicochemical, mechanical, cell viability, etc. The bioactivity test of NFS was evaluated after immersion in SBF (simulated body fluid). NFS from PVA, SF-NFs, HA-NPs, and Cu-NPs exhibited outstanding physicochemical, mechanical, and antibacterial properties. PVA: SF-NFs: HA-NPs: Cu-NPs scaffold excellent antimicrobial performance against E.coli (4.16 ± 0.16 mm) and S.aureus (4.88 ± 0.10 mm). Biocompatibility studies were assessed using human osteosarcoma MG63 cell line, which displayed 100% viable cell presence in PVA: SF-NFs: HA-NPs: Cu-NPs. Based on the characterization, results indicated that they are excellent scaffolds for bone tissue regeneration.

Gamma-Irradiated Bacterial Cellulose as a Three-Dimensional Scaffold for Osteogenic Differentiation of Rat Bone Marrow Stromal Cells

The effect of gamma-irradiation on bacterial cellulose (BC) was investigated in terms of improving its properties as scaffolds for tissue engineering. BC pellicles were exposed to 25, 50, and 75 kGy gamma-ray irradiation, and X-ray diffraction analyses showed that the crystallinity of the BC decreased as stronger irradiation accelerated BC’s degradation. Fourier transform infrared spectroscopy of the irradiated BC revealed the appearance of a new peak at 1724 cm–1, indicating the formation of a new carbonyl group due to the cleavage of glycosidic linkages of the BC. Rat bone marrow stromal cells seeded on the gamma-irradiated BC incubated in an osteogenic medium for 14 days produced calcium, a late marker for osteogenic differentiation, as shown by Alizarin Red S (ARS) staining. Gamma-irradiated BC with higher irradiation doses showed intense ARS staining indicating higher calcium deposition. These findings demonstrate the feasibility of using gamma-irradiated BC as a cytocompatible 3D scaffold for bone tissue regeneration.

Digital light processing (DLP) of nano biphasic calcium phosphate bioceramic for making bone tissue engineering scaffolds

Nano-sized ceramic particles are beneficial for the properties of 3D printed structures via digital light processing (DLP). However, achieving optimal conditions for the preparation and processing of ceramic nanoparticle-based slurry is a significant challenge. In this work, a stable and well dispersed slurry with nano-sized biphasic calcium phosphate (BCP) powders was developed and porous BCP bioceramic scaffolds with good bioactivity were accurately fabricated via the DLP additive manufacturing technology. Effects of dispersant, photoinitiator and solid loading on rheological properties and curing abilities of BCP slurries were systematically studied. The slurry having 65 wt % of nano-sized BCP powders showed a relatively low viscosity of 400 mPa s at the 50 s−1 shear rate. It was found that the optimal photoinitiator concentration was tightly associated with the energy dosage in DLP. Furthermore, the effects of sintering temperature (1100 °C, 1200 °C and 1300 °C) on the surface morphology, shrinkage, phase constitution, hardness, compressive properties, and in vitro biological performance of DLP-formed bioceramics were comprehensively investigated. The results showed that DLP-formed BCP ceramics sintered at 1300 °C had the best mechanical properties, in vitro cytocompatibility, and homogeneous bone-like apatite formation ability. Finally, DLP-formed 3D scaffolds with different pore sizes ranging from 300 μm to 1 mm were successfully fabricated, which exhibited high fidelity and accuracy. The current study has demonstrated the great potential of using DLP technology to construct functional complex BCP bioceramic scaffolds for bone tissue regeneration.

A 3D macroporous and magnetic Mg2SiO4-CuFe2O4 scaffold for bone tissue regeneration: Surface modification, in vitro and in vivo studies.

Macroporous scaffolds with bioactivity and magnetic properties can be a good candidate for bone regeneration and hyperthermia. In addition, modifying the surface of the scaffolds with biocompatible materials can increase their potential for in vivo applications. Here, we developed a multifunctional nanocomposite Mg2SiO4-CuFe2O4 scaffold for bone regeneration and hyperthermia. The surface of scaffold was coated with various concentrations of poly-3-hydroxybutyrate (P3HB, 1-5% (w/v)). It was observed that 3% (w/v) of P3HB provided a favorable combination of porosity (79±2.1%) and compressive strength (3.2±0.11MPa). The hyperthermia potential of samples was assessed in the presence of various magnetic fields in vitro. The coated scaffolds showed a lower degradation rate than the un-coated one up to 35days of soaking in simulated biological medium. Due to the porous and specific morphology of P3HB, it was found that in vitro bioactivity and cell attachment were increased on the scaffold. Moreover, it was observed that the P3HB coating improved the cell viability, alkaline phosphatase activity, and mineralization of the scaffold. Finally, we studied the bone formation ability of the scaffolds in vivo, and implanted the developed scaffold in the rat's femur for 8weeks. Micro-computed tomography results including bone volume fraction and trabecular thickness exhibited an improvement in the bone regeneration of the coated scaffold compared to the control. The overall results of this study introduce a highly macroporous scaffold with multifunctional performance, noticeable ability in bone regeneration, and hyperthermia properties for osteosarcoma.

3D-Printed composite scaffolds based on poly(ε-caprolactone) filled with poly(glutamic acid)-modified cellulose nanocrystals for improved bone tissue regeneration.

The manufacturing of modern scaffolds with customized geometry and personalization has become possible due to the three-dimensional (3D) printing technique. A novel type of 3D-printed scaffolds for bone tissue regeneration based on poly(ε-caprolactone) (PCL) filled with nanocrystalline cellulose modified by poly(glutamic acid) (PGlu-NCC) has been proposed in this study. The 3D printing set-ups were optimized in order to obtain homogeneous porous scaffolds. Both polymer composites and manufactured 3D scaffolds have demonstrated mechanical properties suitable for a human trabecular bone. Compression moduli were in the range of 334-396 MPa for non-porous PCL and PCL-based composites, and 101-122 MPa for porous scaffolds made of the same materials. In vitro mineralization study with the use of human mesenchymal stem cells (hMSCs) revealed the larger Ca deposits on the surface of PCL/PGlu-NCC composite scaffolds. Implantation of the developed 3D scaffolds into femur of the rabbits was carried out to observe close and delayed effects. The histological analysis showed the lowest content of immune cells and thin fibrous capsule, revealing low toxicity of the PCL/PGlu-NCC scaffolds seeded with rabbit MSCs (rMSCs) to the surrounding tissues. The most pronounced result on the generation of new bone tissue after implantation of PCL/PGlu-NCC + rMSCs scaffolds was detected by both microcomputed tomography and histological analysis. Around 33% and 55% of bone coverage were detected for composite 3D scaffolds with adhered rMSCs after 1 and 3months of implantation, respectively. This achievement can be a result of synergistic effect of PGlu, which attracts calcium ions, and stem cells with osteogenic potential.

Hybrid Core-Shell Polymer Scaffold for Bone Tissue Regeneration.

A great promise for tissue engineering is represented by scaffolds that host stem cells during proliferation and differentiation and simultaneously replace damaged tissue while maintaining the main vital functions. In this paper, a novel process was adopted to develop composite scaffolds with a core-shell structure for bone tissue regeneration, in which the core has the main function of temporary mechanical support, and the shell enhances biocompatibility and provides bioactive properties. An interconnected porous core was safely obtained, avoiding solvents or other chemical issues, by blending poly(lactic acid), poly(ε-caprolactone) and leachable superabsorbent polymer particles. After particle leaching in water, the core was grafted with a gelatin/chitosan hydrogel shell to create a cell-friendly bioactive environment within its pores. The physicochemical, morphological, and mechanical characterization of the hybrid structure and of its component materials was carried out by means of infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and mechanical testing under different loading conditions. These hybrid polymer devices were found to closely mimic both the morphology and the stiffness of bones. In addition, in vitro studies showed that the core-shell scaffolds are efficiently seeded by human mesenchymal stromal cells, which remain viable, proliferate, and are capable of differentiating towards the osteogenic phenotype if adequately stimulated.

A Biomimetic Platelet-Rich Plasma-Based Interpenetrating Network Printable Hydrogel for Bone Regeneration.

Repair of bone defects caused by trauma or diseases is the primary focus of prosthodontics. Hydrogels are among the most promising candidates for bone tissue regeneration due to their unique features such as excellent biocompatibility, similarities to biological tissues, and plasticity. Herein, we developed a type of novel biomimetic interpenetrating polymeric network (IPN) hydrogel by combining methacrylated alginate and 4-arm poly (ethylene glycol)-acrylate (4A-PEGAcr) through photo-crosslinking. Platelet-rich plasma (PRP), a patient-specific source of autologous growth factors, was incorporated into the hydrogel, and thereafter the hydrogels were biological mineralized by simulated body fluid (SBF). Physical properties of hydrogels were comprehensively characterized. In vitro studies demonstrated that the incorporation of PRP and biomineralization promoted the biocompatibility of hydrogel. Strikingly, the osteogenic bioactivities, including ALP activity, mineralized nodule formation, and expression of osteogenic markers were found substantially enhanced by this biomineralized PRP-hydrogel. Finally, a rabbit model of bone defect was employed to assess in vivo bone regeneration, micro-CT analysis showed that the biomineralized PRP-hydrogels could significantly accelerate bone generation. We believed that this novel biomineralized PRP-incorporated IPN hydrogel could be promising scaffolds for bone tissue regeneration.

Green synthesis of strontium-reduced graphene oxide biocomposite using gamma radiation

This study presents an environmentally benign approach for synthesizing of strontium nanoparticles-decorated reduced graphene oxide (rGO-Sr) nanosheets using a simple method. Reduced graphene oxide sheets decorated with strontium nanoparticles (rGO-Sr) were used in previous studies in polymer matrices to prepare 3D scaffolds for bone tissue regeneration. Graphene oxide is reduced and strontium nanoparticles have been successfully deposited on it using gamma radiation at room temperature. High-resolution transmission electron microscopy (HR-TEM) analysis assured the formation of strontium nanoparticles (Sr NPs) of 50 nm in size on reduced graphene oxide (rGO) nanosheets. The formed Sr NPs were homogeneously and uniformly distributed on rGO nanosheets forming rGO-Sr nanocomposite. The prepared materials' blood biocompatibility and antibacterial activities against Staphylococcus aureus were studied. The results revealed that the decoration of rGO sheets with strontium nanoparticles offered a significant increase in its antibacterial activity and exhibited good blood biocompatibility. This study shows that graphene-based composite prepared using Sr NPs seems to be a promising antibacterial coating material for biomedical applications.

Additive Manufacturing of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Poly(D,L-lactide-co-glycolide) Biphasic Scaffolds for Bone Tissue Regeneration.

Polyhydroxyalkanoates are biopolyesters whose biocompatibility, biodegradability, environmental sustainability, processing versatility, and mechanical properties make them unique scaffolding polymer candidates for tissue engineering. The development of innovative biomaterials suitable for advanced Additive Manufacturing (AM) offers new opportunities for the fabrication of customizable tissue engineering scaffolds. In particular, the blending of polymers represents a useful strategy to develop AM scaffolding materials tailored to bone tissue engineering. In this study, scaffolds from polymeric blends consisting of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(D,L-lactide-co-glycolide) (PLGA) were fabricated employing a solution-extrusion AM technique, referred to as Computer-Aided Wet-Spinning (CAWS). The scaffold fibers were constituted by a biphasic system composed of a continuous PHBV matrix and a dispersed PLGA phase which established a microfibrillar morphology. The influence of the blend composition on the scaffold morphological, physicochemical, and biological properties was demonstrated by means of different characterization techniques. In particular, increasing the content of PLGA in the starting solution resulted in an increase in the pore size, the wettability, and the thermal stability of the scaffolds. Overall, in vitro biological experiments indicated the suitability of the scaffolds to support murine preosteoblast cell colonization and differentiation towards an osteoblastic phenotype, highlighting higher proliferation for scaffolds richer in PLGA.

Bioactive Cellulose Acetate Electrospun Mats as Scaffolds for Bone Tissue Regeneration.

In the last decades, cell-based approaches for bone tissue engineering (BTE) have relied on using models that cannot replicate the complexity of the bone microenvironment. There is an ongoing amount of research on scaffold development responding to the need for feasible materials that can mimic the bone extracellular matrix (ECM) and aid bone tissue regeneration (BTR). In this work, a porous cellulose acetate (CA) fiber mat was developed using the electrospinning technique and the mats were chemically modified to bioactivate their surface and promote osteoconduction and osteoinduction. The mats were characterized using FTIR and SEM/EDS to validate the chemical modifications and assess their structural integrity. By coupling adhesive peptides KRSR, RGD, and growth factor BMP-2, the fiber mats were bioactivated, and their induced biological responses were evaluated by employing immunocytochemical (ICC) techniques to study the adhesion, proliferation, and differentiation of premature osteoblast cells (hFOB 1.19). The biological assessment revealed that at short culturing periods of 48 hours and 7 days, the presence of the peptides was significant for proliferation and adhesion, whereas at longer culture times of 14 days, it had no significant effect on differentiation and maturation of the osteogenic progenitor cells. Based on the obtained results, it is thus concluded that the CA porous fiber mats provide a promising surface morphology that is both biocompatible and can be rendered bioactive upon the addition of osteogenic peptides to favor osteoconduction leading to new tissue formation.

Novel 3D Bioglass Scaffolds for Bone Tissue Regeneration.

The design of scaffolds with optimal biomechanical properties for load-bearing applications is an important topic of research. Most studies have addressed this problem by focusing on the material composition and not on the coupled effect between the material composition and the scaffold architecture. Polymer–bioglass scaffolds have been investigated due to the excellent bioactivity properties of bioglass, which release ions that activate osteogenesis. However, material preparation methods usually require the use of organic solvents that induce surface modifications on the bioglass particles, compromising the adhesion with the polymeric material thus compromising mechanical properties. In this paper, we used a simple melt blending approach to produce polycaprolactone/bioglass pellets to construct scaffolds with pore size gradient. The results show that the addition of bioglass particles improved the mechanical properties of the scaffolds and, due to the selected architecture, all scaffolds presented mechanical properties in the cortical bone region. Moreover, the addition of bioglass indicated a positive long-term effect on the biological performance of the scaffolds. The pore size gradient also induced a cell spreading gradient.

Methods of producing three dimensional electrospun scaffolds for bone tissue engineering: A review.

Bone is a dynamic, living tissue that exists and renews itself continuously in a 3D manner. Nevertheless, complex clinical conditions require a bone substitute to replace the defective bone and/or accelerate bone healing. Bone tissue engineering aims to treat bone defects that fail to heal on their own. Electrospinning provides an opportunity to create nano- to micro-fibrous scaffolds that mimic the architecture of the natural extracellular matrix (ECM) with high porosity and large specific surface area. Despite these advantages, traditional electrospun meshes can only provide a 2D architecture for cell attachment and proliferation rather than the 3D attachment in native tissue. Fabrication of 3D electrospun scaffolds for bone tissue regeneration is a challenging task, which has attracted significant attention over the past couple of decades. This review highlights recent strategies used to produce 3D electrospun/co-electrospun scaffolds for bone tissue applications describing the materials and procedures. It also considers combining conventional and coaxial electrospinning with other scaffold manufacturing techniques to produce 3D structures which have the potential to engineer missing bone in the human body.Graphical abstract[Formula: see text].

Engineering biomaterials to 3D-print scaffolds for bone regeneration: practical and theoretical consideration.

There are more than 2 million bone grafting procedures performed annually in the US alone. Despite significant efforts, the repair of large segmental bone defects is a substantial clinical challenge which requires bone substitute materials or a bone graft. The available biomaterials lack the adequate mechanical strength to withstand the static and dynamic loads while maintaining sufficient porosity to facilitate cell in-growth and vascularization during bone tissue regeneration. A wide range of advanced biomaterials are being currently designed to mimic the physical as well as the chemical composition of a bone by forming polymer blends, polymer-ceramic and polymer-degradable metal composites. Transforming these novel biomaterials into porous and load-bearing structures via three-dimensional printing (3DP) has emerged as a popular manufacturing technique to develop engineered bone grafts. 3DP has been adopted as a versatile tool to design and develop bone grafts that satisfy porosity and mechanical requirements while having the ability to form grafts of varied shapes and sizes to meet the physiological requirements. In addition to providing surfaces for cell attachment and eventual bone formation, these bone grafts also have to provide physical support during the repair process. Hence, the mechanical competence of the 3D-printed scaffold plays a key role in the success of the implant. In this review, we present various recent strategies that have been utilized to design and develop robust biomaterials that can be deployed for 3D-printing bone substitutes. The article also reviews some of the practical, theoretical and biological considerations adopted in the 3D-structure design and development for bone tissue engineering.

Hybrid scaffolds with a 3D-printed polymer lattice core and a bioactive hydrogel shell for bone regeneration

Recent research in the field of tissue engineering is focusing on the realization of hybrid scaffolds as multi-material systems which allow to successfully combine the advantages of different biomaterials. In addition, additive manufacturing technologies are currently explored for their production, as means to control and personalize the scaffold structure. In this paper, composite scaffolds with a core–shell structure are studied, the core consisting of a rigid poly-l-lactic acid lattice realized by fused deposition modeling, and the shell consisting of a bioactive hydrogel, grafted upon the core and freeze-dried to develop porous microstructure. Different lattice structures are designed and realized as repetition of unit cells having different size and strut arrangement. Compression tests reveal the suitability of the mechanical properties of the scaffolds for bone tissue regeneration, and the possibility to modulate their stiffness and strength upon the lattice parameters. Moreover, the interconnected porous structure of the shell, assessed by morphological analysis at the microscope, may promote cell colonization and proliferation, while its composition may support osteogenic differentiation.

An investigation into the viscoelastic response of chemically and physically crosslinked minimally invasive hydrogel scaffolds

We report development of injectable hydrogels as scaffolds for bone tissue regeneration. An integrated approach has been used to develop the bone scaffolds using nanocellulose (NC), synthesized from agricultural biomass, and poly(vinyl alcohol) (PVA). PVA based hydrogel was formed using physical crosslinking process involving multiple freeze–thaw cycles, while, NC based hydrogel was developed using chemical crosslinking mechanism in which epichlorohydrin was used as a crosslinker. Investigation of micro-structural surface topology was carried out using scanning electron microscopy which indicated favourable environment for cell adhesion. The viscoelastic response characterized using frequency, amplitude and temperature sweeps, demonstrated that within the experimental range, dynamic storage modulus (G’) was considerably higher than dynamic loss modulus (G’’) for all the hydrogel samples, indicating the formation of well-developed network and in turn structural integrity and dynamic stability of the injectable hydrogel scaffolds. Further, the injectable hydrogels demonstrated excellent injectability and self-standing behavior.

3D Printed SiOC(N) Ceramic Scaffolds for Bone Tissue Regeneration: Improved Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.

Bone tissue engineering has developed significantly in recent years as there has been increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone, these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy, and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

Surface Decoration of Redox-Modulating Nanoceria on 3D-Printed Tissue Scaffolds Promotes Stem Cell Osteogenesis and Attenuates Bacterial Colonization.

Oxidative stress at the bone defect site delays the bone regeneration process. Increased level of reactive oxygen species (ROS) is the primary cause of oxidative stress at the damaged site. Bone tissue scaffolds that scavenge ROS offer a potential and yet unexplored route for faster bone healing. Cerium oxide (ceria) is known for its redox-modulating behavior. Three-dimensional (3D)-printed porous scaffolds fabricated from degradable polymers provide a physical microenvironment but lack the bioactivity for tissue regeneration. In this work, porous poly(lactic acid) (PLA) scaffolds were prepared by 3D printing and modified with poly(ethylene imine) and citric acid to decorate with ceria nanoparticles. Scanning electron micrographs revealed a macroporous architecture decorated with ceria particles. The compressive modulus of 27 MPa makes them suitable for trabecular bone. The scaffolds supported human mesenchymal stem cell growth, confirming cytocompatibility. The ability to scavenge ROS confirmed that surface functionalization with ceria could reduce oxidative stress levels in the cells. Stem cell osteogenesis was enhanced after ceria decoration of the PLA scaffolds. Transcriptional profiling studied by sequencing revealed changes in the expression of genes associated with inflammation and cell-material interactions. The ceria-functionalized scaffolds show enhanced antibacterial activity against both Gram-negative and Gram-positive bacterial strains. These results demonstrate that surface decoration with nanoceria offers a viable route for enhancing the bioactivity of 3D-printed PLA scaffolds for bone tissue regeneration with ROS scavenging and antibacterial capability.

Comparative Study of Crystallization, Mechanical Properties, and In Vitro Cytotoxicity of Nanocomposites at Low Filler Loadings of Hydroxyapatite for Bone-Tissue Engineering Based on Poly(l-lactic acid)/Cyclo Olefin Copolymer.

A poly(l-lactic acid)/nanohydroxyapatite (PLLA/nHA) scaffold works as a bioactive, osteoconductive scaffold for bone-tissue engineering, but its low degradation rate limits embedded HA in PLLA to efficiently interact with body fluids. In this work, nano-hydroxyapatite (nHA) was added in lower filler loadings (1, 5, 10, and 20 wt%) in a poly(l-lactic acid)/cyclo olefin copolymer10 wt% (PLLA/COC10) blend to obtain novel poly(l-lactic acid)/cyclo olefin copolymer/nanohydroxyapatite (PLLA/COC10-nHA) scaffolds for bone-tissue regeneration and repair. Furthermore, the structure-activity relationship of PLLA/COC10-nHA (ternary system) nanocomposites in comparison with PLLA/nHA (binary system) nanocomposites was systematically studied. Nanocomposites were evaluated for structural (morphology, crystallization), thermomechanical properties, antibacterial potential, and cytocompatibility for bone-tissue engineering applications. Scanning electron microscope images revealed that PLLA/COC10-nHA had uniform morphology and dispersion of nanoparticles up to 10% of HA, and the overall nHA dispersion in matrix was better in PLLA/COC10-nHA as compared to PLLA/nHA. Fourier transformation infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC) studies confirmed miscibility and transformation of the α-crystal form of PLLA to the ά-crystal form by the addition of nHA in all nanocomposites. The degree of crystallinity (%) in the case of PLLA/COC10-nHA 10 wt% was 114% higher than pure PLLA/COC10 and 128% higher than pristine PLLA, indicating COC and nHA are acting as nucleating agents in the PLLA/COC10-nHA nanocomposites, causing an increase in the degree of crystallinity (%). Moreover, PLLA/COC10-nHA exhibited 140 to 240% (1–20 wt% HA) enhanced mechanical properties in terms of ductility as compared to PLLA/nHA. Antibacterial activity results showed that 10 wt% HA in PLLA/COC10-nHA showed substantial activity against P. aeruginosa, S. aureus, and L. monocytogenes. In vitro cytocompatibility of PLLA/COC10 and PLLA nanocomposites with nHA osteoprogenitor cells (MC3T3-E1) and bone mesenchymal stem cells (BMSC) was evaluated. Both cell lines showed two- to three-fold enhancement in cell viability and 10- to 30-fold in proliferation upon culture on PLLA/COC10-nHA as compared to PLLA/nHA composites. It was observed that the ternary system PLLA/COC10-nHA had good dispersion and interfacial interaction resulting in improved thermomechanical and enhanced osteoconductive properties as compared to PLLA/nHA.