Unmodified Scaffolds Research Articles

3D printed TC4 titanium alloy bone scaffolds with TNTs-VA-PLGA composite coating on the surface:improved infection resistance and biocompatibility

Titanium-based bone scaffolds are prone to aseptic infection and loosening after implantation,which seriously limits their clinical applications. Preparation of titanium dioxide nanotubes (TNTs) on the surface of the scaffolds and loading of anti-infective drugs is an effective method to solve this problem, but the current TNTs prepared on the surface of titanium-based scaffolds have a high internal and external variability in morphology and low drug loading capacity. In this study, we prepared TNTs on the surface of three kinds of TC4 titanium alloy scaffolds with TPMS structure with controllable morphology, tube diameter of 90-125 nm and tube length of 14-35 μm,and the difference between inner and outer diameters of the tubes was less than 2 μm,and the drug released from the composite scaffolds was maintained at a concentration of more than 1.5 μg/ml within 11 days after loading anti-infective drug Vancomycin-polylactic acid-hydroxyacetic acid copolymer(VA-PLGA) on the surface of the TNTs. Based on the simulation of drug release, the TNTs-VA-PLGA drug delivery system conforms to the Korsmeyer-Peppas model. Cell experiments confirmed that the composite scaffolds significantly increased cell proliferation by 65.33% compared with the unmodified scaffolds. The results indicated that the TNTs coating containing vancomycin and polylactic acid-hydroxyacetic acid copolymer had a promising application in orthopedic implants.

An immunomodulatory and osteogenic bacterial cellulose scaffold for bone regeneration via regulating the immune microenvironment

Creating a bone homeostasis microenvironment that balances osteogenesis and immunity is a substantial challenge for bone regeneration. Here, we prepared an immunomodulatory and osteogenic bacterial cellulose scaffold (FOBS) via a facile one-pot approach. The aldehyde groups were generated via selective oxidation of the hydroxyl groups of bacterial cellulose, offering the bonding sites for dopamine through a Schiff base reaction. At the same time, the deposition of Ca2+ and PO43− was promoted on the aldehyde cellulose scaffold because of the high affinity of the catechol moiety for Ca2+. Compared with that of the unmodified scaffold, the hydroxyapatite content of FOBS increased by 47.1 % according to the ICP results. Interestingly, FOBS regulated the immune microenvironment to accelerate the conversion of M1 to M2 macrophages. The expressions of ARG-1 and Dectin-1 (M2) in the FOBS group increased by >100 %. The expression of osteogenic differentiation of BMSCs was also upregulated. In a rat cranial defect model, the BV/TV of FOBS was significantly increased. Further immunohistochemical analysis revealed that an improved immune microenvironment promoted the osteogenic differentiation of stem cells in vivo. This work provides an effective and easy-to-operate strategy for the development of the bone tissue engineering scaffolds.

Nanomechanical mapping of PLA hydroxyapatite composite scaffolds links surface homogeneity to stem cell differentiation

Polymer composite scaffolds hold promise in bone tissue engineering due to their biocompatibility, mechanical properties, and reproducibility. Among these materials, polylactic acid (PLA), a biodegradable plastics has gained attention for its processability characteristics. However, a deeper understanding of how PLA scaffold surface properties influence cell behavior is enssential for advancing its applications. In this study, 3D-printed PLA scaffolds containing hydroxyapatite (HA) were analyzed using atomic force microscopy and nanomechanical mapping. The addition of HA significantly increased key surface properties compared to unmodified PLA scaffols. Notably, the HA-modified scaffold demonstrated Gaussian distribution of stiffness and adhesive forces, in contrast to the bimodal properties observed in the unmodified PLA scaffolds. Human adipose-derived mesenchymal stem cell (hADMSC) seeded on the 3D-printed PLA scaffolds blended with 10% HA (P10) exhibited strong attachment. After four weeks, osteogenic differentiation of hADMSCs was detected, with calcium deposition reaching 6.76% ± 0.12. These results suggest that specific ranges of stiffness and adhesive forces of the composite scaffold can support cell attachement, and mineralization. The study highlights that tailoring suface properties of composite scaffolds is crucial for modulating cellular interactions, thus advancing the development of effective bone replacement materials.

Bovine serum albumin-modified 3D printed alginate dialdehyde-gelatin scaffolds incorporating polydopamine/SiO2-CaO nanoparticles for bone regeneration

Three-dimensional (3D) printing allows precise manufacturing of bone scaffolds for patient-specific applications and is one of the most recently developed and implemented technologies. In this study, bilayer and multimaterial alginate dialdehyde-gelatin (ADA-GEL) scaffolds incorporating polydopamine (PDA)/SiO2-CaO nanoparticle complexes were 3D printed using a pneumatic extrusion-based 3D printing technology and further modified on the surface with bovine serum albumin (BSA) for application in bone regeneration. The morphology, chemistry, and in vitro bioactivity of PDA/SiO2-CaO nanoparticle complexes were characterized (n = 3) and compared with those of mesoporous SiO2-CaO nanoparticles. Successful deposition of the PDA layer on the surface of the SiO2-CaO nanoparticles allowed better dispersion in a liquid medium and showed enhanced bioactivity. Rheological studies (n = 3) of ADA-GEL inks consisting of PDA/SiO2-CaO nanoparticle complexes showed results that may indicate better injectability and printability behavior compared to ADA-GEL inks incorporating unmodified nanoparticles. Microscopic observations of 3D printed scaffolds revealed that PDA/SiO2-CaO nanoparticle complexes introduced additional topography onto the surface of 3D printed scaffolds. Additionally, the modified scaffolds were mechanically stable and elastic, closely mimicking the properties of natural bone. Furthermore, protein-coated bilayer scaffolds displayed controllable absorption and biodegradation, enhanced bioactivity, MC3T3-E1 cell adhesion, proliferation, and higher alkaline phosphatase (ALP) activity (n = 3) compared to unmodified scaffolds. Consequently, the present results confirm that ADA-GEL scaffolds incorporating PDA/SiO2-CaO nanoparticle complexes modified with BSA offer a promising approach for bone regeneration applications.

Polyelectrolyte Multilayer Coating on 3D Printed PEGDA/TCP Scaffold with Improved Cell Proliferation

Bioactive coating of ceramic scaffolds is an effective way to ameliorate osseointegration and attenuate implant-induced inflammatory responses, which should be biocompatible and possess suitable mechanical properties to regulate cell adhesion and migration. In this study, a poly (ethylene glycol) diacrylate/tricalcium phosphate (PEGDA/TCP) ceramic scaffold was prepared using SLA-3D printing, and its compressive strength was 8.9 ± 1.0 MPa. Chitosan (Chi) and chondroitin sulfate (CS) were assembled on the surface of the PEGDA/TCP scaffolds and crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) -carbodiimide/ N-hydroxysuccinimide (EDC/NHS). Scanning electron microscope (SEM), Fourier transform infrared (FTIR), and laser scanning microscope were used to evaluate the surface modification of the PEGDA/TCP scaffolds. Cellular tests showed that polyelectrolyte multilayers (PEMs) promoted cell adhesion and proliferation of osteoblasts relative to unmodified scaffolds. Furthermore, it can be demonstrated that the SLA-3D printed TCP scaffolds could meet the compressive requirements of trabecular bones, and the bioactivity of the bone scaffolds could be effectively improved by combining them with Chi/CS PEM.

Fabrication and Characterization of a Polydopamine-Modified Bacterial Cellulose and Sugarcane Filter Cake-Derived Hydroxyapatite Composite Scaffold.

The search for environmentally friendly and sustainable sources of raw materials has been ongoing for quite a while, and currently, the utilization and applications of agro-industrial biomass residues in biomedicine are being researched. In this study, a polydopamine (PDA)-modified bacterial cellulose (BC) and hydroxyapatite (HA) composite scaffold was fabricated using the freeze-drying method. The as-prepared hydroxyapatite was synthesized via the chemical precipitation method using sugarcane filter cake as a calcium source, as reported in a previous study. X-ray diffraction analysis revealed a carbonated phase of the prepared hydroxyapatite, similar to that of the natural bone mineral. Wide-angle X-ray scattering analysis revealed the successful fabrication of BC/HA composite scaffolds, while X-ray photoelectron spectroscopy suggested that PDA was deposited on the surface of the BC/HA composite scaffolds. In vitro cell viability assays indicated that BC/HA and PDA-modified composite scaffolds did not induce cytotoxicity and were biocompatible with MC3T3-E1 preosteoblasts. PDA-modified composite scaffolds showed enhanced protein adsorption capacity in vitro compared to the unmodified scaffolds. On a concluding note, these results demonstrate that agro-industrial biomass residues have the potential to be used in biomedical applications and that PDA-modified BC/HA composite scaffolds are a promising biomaterial for bone tissue engineering.

Aminosilane Functionalized Aligned Fiber PCL Scaffolds for Peripheral Nerve Repair.

Silane modification is a simple and cost-effective tool to modify existing biomaterials for tissue engineering applications. Aminosilane layer deposition has previously been shown to control NG108-15 neuronal cell and primary Schwann cell adhesion and differentiation by controlling deposition of ─NH2 groups at the submicron scale across the entirety of a surface by varying silane chain length. This is the first study toreport depositing 11-aminoundecyltriethoxysilane (CL11) onto aligned Polycaprolactone (PCL) scaffolds for peripheral nerve regeneration. Fibers are manufactured via electrospinning and characterized using water contact angle measurements, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). Confirmed modified fibers are investigated using in vitro cell culture of NG108-15 neuronal cells and primary Schwann cells to determine cell viability, cell differentiation, and phenotype. CL11-modified fibers significantly support NG108-15 neuronal cell and Schwann cell viability. NG108-15 neuronal cell differentiation maintains Schwann cell phenotype compared to unmodified PCL fiber scaffolds. 3D ex vivo culture of Dorsal root ganglion explants (DRGs) confirms further Schwann cell migration and longer neurite outgrowth from DRG explants cultured on CL11 fiber scaffolds compared to unmodified scaffolds. Thus, a reproducible and cost-effective tool is reported to modify biomaterials with functional amine groups that can significantly improve nerve guidance devices and enhance nerve regeneration.

Bioinspired nanotopography on 3D printed tissue scaffold to impart mechanobactericidal and osteogenic activities

The great demand for bone grafts has motivated the development of tissue scaffolds with osteogenic activity, whereas the risk of implant-associated infection, especially given the rise of antimicrobial resistance, has compelled the development of scaffolds with innovative antimicrobial strategies. Bioinspired mechanobactericidal nanostructures are highly appealing as an alternative to traditional chemical approaches. This study presents an innovative spin-coating setup for the generation of nanotopography on the surfaces of a three-dimensional (3D)-printed porous polylactide (PLA) scaffold based on the principle of polymer demixing. The nanostructured PLA surface exhibited excellent bactericidal activity by contact killing of P. aeruginosa (86.60 % dead cells in 24 h) and S. aureus (92.36 %). The nanoscale topography supported the attachment and proliferation of pre-osteoblasts and better supported osteogenic differentiation than the unmodified scaffold. These findings demonstrate a single-step spin coating to yield nanotopography on 3D-printed polymer scaffolds that concurrently impart mechanobactericidal and osteogenic activities. Taken together, this work has important implications for engineering the next-generation 3D printed bioactive tissue scaffolds.

Enhanced Cell Penetration and Pluripotency Maintenance of hiPSCs in 3D Natural Chitosan Scaffolds.

Human induced pluripotent stem cells (hiPSCs) cultured in three-dimensional (3D) matrices hold great promise in disease modeling, drug discovery and tissue regeneration. Uniform cell distribution in a 3D structure is critical to the growth and function of hiPSCs, yet cell seeding in 3D matrices often remains superficial, leading to limited cell proliferation and compromised pluripotency. Here, we report an approach to improve cell penetration depth of hiPSCs in 3D scaffolds modified with hiPSCs conditioned medium (CM). We showed that extra-cellular matrix (ECM) components were successfully deposited onto the scaffold wall surface after CM treatment and promoted homogeneous cell adhesion during initial seeding. Compared to plain, unmodified scaffolds, the CM treated scaffold improved spatial cell distribution uniformity and upregulated pluripotency markers. Notably, the expression of 29 genes associated with 11 signaling pathways participated in the pluripotency maintenance of hiPSCs exhibited > 2-fold change in hiPSCs grown in the CM treated scaffolds than 2D counterparts, demonstrating that CM treated scaffolds can support a more primitive and undifferentiated phenotype of hiPSCs. This study introduced a simple and effective method to enhance cell penetration and maintain cell pluripotency in 3D matrices. This article is protected by copyright. All rights reserved.

Collagen Functionalization of Polymeric Electrospun Scaffolds to Improve Integration into Full-Thickness Wounds.

Electrospun fibers are widely studied in regenerative medicine for their ability to mimic the extracellular matrix (ECM) and provide mechanical support. In vitro studies indicated that cell adhesion and migration is superior on smooth poly(L-lactic acid) (PLLA) electrospun scaffolds and porous scaffolds once biofunctionalized with collagen. The in vivo performance of PLLA scaffolds with modified topology and collagen biofunctionalization in full-thickness mouse wounds was assessed by cellular infiltration, wound closure and re-epithelialization and ECM deposition. Early indications suggested unmodified, smooth PLLA scaffolds perform poorly, with limited cellular infiltration and matrix deposition around the scaffold, the largest wound area, a significantly larger panniculus gape, and lowest re-epithelialization; however, by day 14, no significant differences were observed. Collagen biofunctionalization may improve healing, as collagen-functionalized smooth scaffolds were smallest overall, and collagen-functionalized porous scaffolds were smaller than non-functionalized porous scaffolds; the highest re-epithelialization was observed in wounds treated with collagen-functionalized scaffolds. Our results suggest that limited incorporation of smooth PLLA scaffolds into the healing wound occurs, and that altering surface topology, particularly by utilizing collagen biofunctionalization, may improve healing. The differing performance of the unmodified scaffolds in the in vitro versus in vivo studies demonstrates the importance of preclinical testing.

The Impact of Polyethylene Glycol-Modified Chitosan Scaffolds on the Proliferation and Differentiation of Osteoblasts.

The objective of this study was to investigate the influence of polyethylene glycol (PEG) incorporated chitosan scaffolds on osteoblasts proliferation and differentiation. The chitosan polymer was initially modified by the predetermined concentration of the photoreactive azido group for UV-crosslinking and with RGD peptides (N-acetyl-GRGDSPGYG-amide). The PEG was mixed at different ratios (0, 10, and 20 wt%) with modified chitosan in 96-well tissue culture polystyrene plates to prepare CHI-100, CHI-90, and CHI-80 scaffolds. PEG-containing scaffolds exhibited bigger pore size and higher water content compared to unmodified chitosan scaffolds. After 10 days of incubation, the cell number of CHI-90 (1.1 × 106 cells/scaffold) surpasses that of CHI-100 (9.2 × 105 cells/scaffold) and the cell number of CHI-80 (7.6 × 105 cells/scaffold) were significantly lower. The ALP activity of CHI-90 was the highest on the fifth day indicating the favored osteoblasts' early-stage differentiation. Moreover, after 14 days of osteogenic culture, calcium deposition in the CHI-90 scaffolds (2.7 μmol Ca/scaffold) was significantly higher than the control (2.2 μmol Ca/scaffold) whereas on CHI-80 was 1.9 μmol/scaffold. The results demonstrate that PEG-incorporated chitosan scaffolds favored osteoblasts proliferation and differentiation; however, mixing relatively excess PEG (≥20% wt.) had a negative impact on osteoblasts proliferation and differentiation.

Effect of carbon spacer length on the antibacterial properties of zwitterionic poly(sulfobetaine) type copolymeric brushes and their application in wound healing.

Creating infection resistant polymer brushes possessing antiadhesive, bactericidal and cell-compatible features can be regarded as a promising approach to prevent biomaterial-associated infections. In this work, polysulfobetaine type zwitterionic homo- and copolymer brushes with varying spacer lengths (charge separation distance between zwitterions, n = 3, 6 or 12) were allowed to grow onto a tartaric acid based aliphatic polyester substrate using surface initiated atom transfer radical polymerization. All of the brush modified surfaces were thoroughly characterized and assessed for their anti-infective performances in vitro. Strikingly, a suitable copolymer composition, i.e., polyZ6-co-Z12 (50/50 copolymer of polysulfobetaine methacrylates with 6 and 12 spacer lengths), was observed to inhibit bacterial growth completely and its activity was sustained for a long time (>3 months). Surprisingly, its antibacterial effect was found to be bactericidal, as is evident from live-dead staining of residual dead bacterial cells that can be easily released by exposing the surface to salt solution, thereby regenerating the surface. However, all of the other copolymer as well as homopolymer brushes exhibited bacteriostatic behavior. An attempt was made to understand the peculiar behavior of this particular brush composition. Nevertheless, the biocidal and also protein repellent brush did not display any cytotoxicity towards human cells, making it an ideal substrate to be used as an infection resistant biomedical implant. Animal studies further confirmed that this particular copolymeric brush modified scaffold can be a promising anti-infective wound dressing material with rapid wound healing effects as compared to the unmodified scaffold.

Mitigation of Cellular and Bacterial Adhesion on Laser Modified Poly (2-Methacryloyloxyethyl Phosphorylcholine)/Polydimethylsiloxane Surface

Nowadays, using polymers with specific characteristics to coat the surface of a device to prevent undesired biological responses can represent an optimal strategy for developing new and more efficient implants for biomedical applications. Among them, zwitterionic phosphorylcholine-based polymers are of interest due to their properties to resist cell and bacterial adhesion. In this work, the Matrix-Assisted Laser Evaporation (MAPLE) technique was investigated as a new approach for functionalising Polydimethylsiloxane (PDMS) surfaces with zwitterionic poly(2-Methacryloyloxyethyl-Phosphorylcholine) (pMPC) polymer. Evaluation of the physical-chemical properties of the new coatings revealed that the technique proposed has the advantage of achieving uniform and homogeneous stable moderate hydrophilic pMPC thin layers onto hydrophobic PDMS without any pre-treatment, therefore avoiding the major disadvantage of hydrophobicity recovery. The capacity of modified PDMS surfaces to reduce bacterial adhesion and biofilm formation was tested for Gram-positive bacteria, Staphylococcus aureus (S. aureus), and Gram-negative bacteria, Escherichia coli (E. coli). Cell adhesion, proliferation and morphology of human THP-1 differentiated macrophages and human normal CCD-1070Sk fibroblasts on the different surfaces were also assessed. Biological in vitro investigation revealed a significantly reduced adherence on PDMS-pMPC of both E. coli (from 29 × 10 6 to 3 × 102 CFU/mL) and S. aureus (from 29 × 106 to 3 × 102 CFU/mL) bacterial strains. Additionally, coated surfaces induced a significant inhibition of biofilm formation, an effect observed mainly for E. coli. Moreover, the pMPC coatings improved the capacity of PDMS to reduce the adhesion and proliferation of human macrophages by 50% and of human fibroblast by 40% compared to unmodified scaffold, circumventing undesired cell responses such as inflammation and fibrosis. All these highlighted the potential for the new PDMS-pMPC interfaces obtained by MAPLE to be used in the biomedical field to design new PDMS-based implants exhibiting long-term hydrophilic profile stability and better mitigating foreign body response and microbial infection.

Lipid Nanoparticles and Liposomes for Bone Diseases Treatment.

Because of their outstanding biocompatibility, sufficient capacity to control drug release, and passive targeting capability, lipid nanoparticles are one of the world's most widely utilized drug delivery systems. However, numerous disadvantages limit the use of lipid nanoparticles in clinical settings, especially in bone regeneration, such as challenges in transporting, storing, and maintaining drug concentration in the local area. Scaffolds are frequently employed as implants to provide mechanical support to the damaged area or as diagnostic and imaging tools. On the other hand, unmodified scaffolds have limited powers in fostering tissue regeneration and curing illnesses. Liposomes offer a solid foundation for the long-term development of various commercial solutions for the effective drug delivery-assisted treatment of medical conditions. As drug delivery vehicles in medicine, adjuvants in vaccination, signal enhancers/carriers in medical diagnostics and analytical biochemistry, solubilizers for various ingredients as well as support matrices for various ingredients, and penetration enhancers in cosmetics are just a few of the industrial applications for liposomes. This review introduces and discusses the use of lipid nanoparticles and liposomes and the application of lipid nanoparticles and liposome systems based on different active substances in bone diseases.

Fluconazole-loaded TEOS-modified nanocellulose 3D scaffolds – Fabrication, characterization and its application as vaginal drug delivery system

The present research utilizes the nanocellulose extracted from rice or wheat straw and modified using tetraethyl orthosilicate (TEOS). The 2-factor 3-level central composite experimental design was employed to prepare lyophilized 3D scaffolds containing fluconazole, as a model drug. The optimal batch of scaffolds contains nanocellulose (10%w/v), fluconazole (1%w/v), and TEOS (6%v/v for rice nanocellulose and 7.7%v/v for wheat nanocellulose). The silicane modification was confirmed by infrared and EDX spectra. The thermal studies, diffraction patterns and electron micrographs revealed the increase in thermal stability, amorphous nature, and porous framework of 3D scaffolds. The TEOS-modified nanocellulose scaffolds exhibited greater swelling, porosity, and tensile strength over unmodified scaffolds. The optimal batch of modified scaffolds released 99% of fluconazole over 24 h, while, the ex-vivo vaginal permeation revealed 1.23-fold greater permeation of fluconazole. The 3D scaffolds show more antifungal activity with no change in cytotoxicity of fluconazole. The scaffolds were found to be histologically safe.

Mussel-Inspired Polydopamine-Based Multilayered Coatings for Enhanced Bone Formation.

Repairing bone defects remains a challenge in clinical practice and the application of artificial scaffolds can enhance local bone formation, but the function of unmodified scaffolds is limited. Considering different application scenarios, the scaffolds should be multifunctionalized to meet specific demands. Inspired by the superior adhesive property of mussels, polydopamine (PDA) has attracted extensive attention due to its universal capacity to assemble on all biomaterials and promote further adsorption of multiple external components to form PDA-based multilayered coatings with multifunctional property, which can induce synergistic enhancement of new bone formation, such as immunomodulation, angiogenesis, antibiosis and antitumor property. This review will summarize mussel-inspired PDA-based multilayered coatings for enhanced bone formation, including formation mechanism and biofunction of PDA coating, as well as different functional components. The synergistic enhancement of multiple functions for better bone formation will also be discussed. This review will inspire the design and fabrication of PDA-based multilayered coatings for different application scenarios and promote deeper understanding of their effect on bone formation, but more efforts should be made to achieve clinical translation. On this basis, we present a critical conclusion, and forecast the prospects of PDA-based multilayered coatings for bone regeneration.

Fibrous 3D printed poly(ɛ)caprolactone tissue engineering scaffold for in vitro cell models

One of the most challenging goals of tissue engineering is the search for efficient but simple production methods of 3D cell culture scaffolds. We fabricated novel microfibrous PCL scaffolds using a commercial 3D printer modified with a melt electrospun process. The microfibrous PCL scaffolds featured fibres with width ranging between 10 and 190 µm in pores between 14 and 570 µm, and overall thickness ranging from 250 to 2000 µm, depending on the selected process parameters. The hydrophilicity of the scaffolds was improved by the surface post-treatment using an alkaline treatment with NaOH, reducing the WCA from 124 ± 4° (unmodified scaffold) to 58 ± 3° (after 8 min of submersion). The scaffold biocompatibility was further increased by coating of fibre surface with collagen I isolated from bovine. The triple-negative breast cancer human breast cancer cell line MDA-MB-231 was chosen as a model cell line for testing cell proliferation by MTT assay. The scaffold successfully supported the cellular growth and viability. The interconnected porosity and an ECM-like Collagen-I covering increased cellular adherence, penetration, and proliferation from the first days after cell seeding. The results demonstrated that such production method of the fibrous PCL scaffold has great potential for scaffold preparation for tissue engineering.

Immune-instructive copolymer scaffolds using plant-derived nanoparticles to promote bone regeneration

BackgroundAge-driven immune signals cause a state of chronic low-grade inflammation and in consequence affect bone healing and cause challenges for clinicians when repairing critical-sized bone defects in elderly patients.MethodsPoly(l-lactide-co-ɛ-caprolactone) (PLCA) scaffolds are functionalized with plant-derived nanoparticles from potato, rhamnogalacturonan-I (RG-I), to investigate their ability to modulate inflammation in vitro in neutrophils and macrophages at gene and protein levels. The scaffolds’ early and late host response at gene, protein and histological levels is tested in vivo in a subcutaneous rat model and their potential to promote bone regeneration in an aged rodent was tested in a critical-sized calvaria bone defect. Significant differences were tested using one-way ANOVA, followed by a multiple-comparison Tukey’s test with a p value ≤ 0.05 considered significant.ResultsGene expressions revealed PLCA scaffold functionalized with plant-derived RG-I with a relatively higher amount of galactose than arabinose (potato dearabinated (PA)) to reduce the inflammatory state stimulated by bacterial LPS in neutrophils and macrophages in vitro. LPS-stimulated neutrophils show a significantly decreased intracellular accumulation of galectin-3 in the presence of PA functionalization compared to Control (unmodified PLCA scaffolds). The in vivo gene and protein expressions revealed comparable results to in vitro. The host response is modulated towards anti-inflammatory/ healing at early and late time points at gene and protein levels. A reduced foreign body reaction and fibrous capsule formation is observed when PLCA scaffolds functionalized with PA were implanted in vivo subcutaneously. PLCA scaffolds functionalized with PA modulated the cytokine and chemokine expressions in vivo during early and late inflammatory phases. PLCA scaffolds functionalized with PA implanted in calvaria defects of aged rats downregulating pro-inflammatory gene markers while promoting osteogenic markers after 2 weeks in vivo.ConclusionWe have shown that PLCA scaffolds functionalized with plant-derived RG-I with a relatively higher amount of galactose play a role in the modulation of inflammatory responses both in vitro and in vivo subcutaneously and promote the initiation of bone formation in a critical-sized bone defect of an aged rodent. Our study addresses the increasing demand in bone tissue engineering for immunomodulatory 3D scaffolds that promote osteogenesis and modulate immune responses.

Bioceramic Scaffolds with Antioxidative Functions for ROS Scavenging and Osteochondral Regeneration.

Osteoarthritis (OA) is a degenerative disease that involves excess reactive oxygen species (ROS) and osteochondral defects. Although multiple approaches have been developed for osteochondral regeneration, how to balance the biochemical and physical microenvironment in OA remains a big challenge. In this study, a bioceramic scaffold by 3D printed akermanite (AKT) integrated with hair‐derived antioxidative nanoparticles (HNPs)/microparticles (HMPs) for ROS scavenging and osteochondral regeneration has been developed. The prepared bioscaffold with multi‐mimetic enzyme effects, which can scavenge a broad spectrum of free radicals in OA, can protect chondrocytes under the ROS microenvironment. Importantly, the bioscaffold can distinctly stimulate the proliferation and maturation of chondrocytes due to the stimulation of the glucose transporter pathway (GLUT) via HNPs/HMPs. Furthermore, it significantly accelerated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo results showed that the bioscaffold can effectively enhance the osteochondral regeneration compared to the unmodified scaffold. The work shows that integration of antioxidant and mechanical properties via the bioscaffold is a promising strategy for osteochondral regeneration in OA treatment.

Antibacterial Honeycomb Scaffolds for Achieving Infection Prevention and Bone Regeneration

Surgical site infection (SSI) is a severe complication associated with orthopedic bone reconstruction. For both infection prevention and bone regeneration, the framework surface of osteoconductive and bioresorbable scaffolds must be locally modified by minimum antibacterial substances, without sacrificing the osteoconductivity of the scaffold framework. In this study, we fabricated antibacterial honeycomb scaffolds by replacing carbonate apatite, which is the main component of the scaffold, with silver phosphate locally on the scaffold surface via dissolution-precipitation reactions. When the silver content was 9.9 × 10-4 wt %, the honeycomb scaffolds showed antibacterial activity without cytotoxicity and allowed cell proliferation, differentiation, and mineralization. Furthermore, the antibacterial honeycomb scaffolds perfectly prevented bacterial infection in vivo in the presence of methicillin-resistant Staphylococcus aureus, formed new bone at 2 weeks after surgery, and were gradually replaced with a new bone. Thus, the antibacterial honeycomb scaffolds achieved both infection prevention and bone regeneration. In contrast, severe infection symptoms, including abscess formation, osteolytic lesions, and inflammation, occurred 2 weeks after surgery when honeycomb scaffolds without silver phosphate modification were implanted. Nevertheless, the unmodified honeycomb scaffolds eliminated bacteria and necrotic bone through their scaffold channels, resulting in symptom improvement and bone formation. These results suggest that the honeycomb structure is inherently effective in hindering bacterial growth. This novel insight may contribute to the development of antibacterial scaffolds. Moreover, our modification method is useful for providing antibacterial activity to various biomaterials.