Journal of biomedical materials research. Part A最新文献

Despite the attractive combinations of cell/surface interactions, biocompatibility, and good mechanical properties of Ti-6Al-4V, there is still a need to enhance the early stages of cell/surface integration that are associated with the implantation of biomedical devices into the human body. This paper presents a novel, easy and reproducible method of nanoscale and nanostructured hydroxyapatite (HA) coatings on Ti-6Al-4V. The resulting nanoscale coatings/nanostructures are characterized using a combination of Raman spectroscopy, scanning electron microscopy equipped with energy dispersive x-ray spectroscopy. The nanostructured/nanoscale coatings are shown to enhance the early stages of cell spreading and integration of bone cells (hFOB cells) on Ti-6Al-4V surfaces. The improvements include the acceleration of extra-cellular matrix, cell spreading and proliferation by nanoscale HA structures on the coated surfaces. The implications of the results are discussed for the development of HA nanostructures for the improved osseointegration of Ti-6Al-4V in orthopedic and dental applications.

Diabetic foot ulcers are a serious complication of uncontrolled diabetes, emphasizing the need to develop wound healing strategies that are not only effective but also biocompatible, biodegradable, and safe. We aimed to create biomatrices composed of semi-interpenetrated polymer networks of collagen, polyurethane, and dextran, to enhance the wound healing process. The hydrogels were extensively characterized by various analytical techniques, including analysis of their structure, crystallinity, thermal properties, gelation process, reticulation, degradation, cell proliferation, and healing properties, among others. Semi-interpenetrated hydrogels containing dextran at levels of 10%, 20%, and 30% exhibited porous interconnections between collagen fibers and entrapped dextran granules, with a remarkable crosslinking index of up to 94% promoted by hydrogen bonds. These hydrogels showed significant improvements in mechanical properties, swelling, and resistance to proteolytic and hydrolytic degradation. After 24 h, there was a significant increase in the viability of several cell types, including RAW 264.7 cells, human peripheral blood mononuclear cells, and dermal fibroblasts. In addition, these hydrogels demonstrated an increased release of interleukin-10 and transforming growth factor-beta1 while inhibiting the release of monocyte chemotactic protein-1 and tumor necrosis factor-alpha after 72 h. Furthermore, these hydrogels accelerated the wound healing process in diabetic rats after topical application. Notably, the biomaterial with 20% dextran (D20) facilitated wound closure in only 21 days. These results highlight the potential of the D20 hydrogel, which exhibits physicochemical and biological properties that enhance wound healing by inhibiting inflammation and fibrillogenesis while remaining safe for application to the skin.

Critically-sized segmental bone defects represent significant challenges requiring grafts for reconstruction. 3D-printed synthetic bone grafts are viable alternatives to structural allografts if engineered to provide appropriate mechanical performance and osteoblast/osteoclast cell responses. Novel 3D-printable nanocomposites containing acrylated epoxidized soybean oil (AESO) or methacrylated AESO (mAESO), polyethylene glycol diacrylate, and nanohydroxyapatite (nHA) were produced using masked stereolithography. The effects of volume fraction of nHA and methacrylation of AESO on interactions of differentiated MC3T3-E1 osteoblast (dMC3T3-OB) and differentiated RAW264.7 osteoclast cells with 3D-printed nanocomposites were evaluated in vitro and compared with a control biomaterial, hydroxyapatite (HA). Higher nHA content and methacrylation significantly improved the mechanical properties. All nanocomposites supported dMC3T3-OB cells' adhesion and proliferation. Higher amounts of nHA enhanced cell adhesion and proliferation. mAESO in the nanocomposites resulted in greater adhesion, proliferation, and activity at day 7 compared with AESO nanocomposites. Excellent osteoclast-like cells survival, defined actin rings, and large multinucleated cells were only observed on the high nHA fraction (30%) mAESO nanocomposite and the HA control. Thus, mAESO-based nanocomposites containing higher amounts of nHA have better interactions with osteoblast-like and osteoclast-like cells, comparable with HA controls, making them a potential future alternative graft material for bone defect repair.

The 0106-B1-bioactive glass (BG) composition (in wt %: 37.5 SiO₂, 22.6 CaO, 5.9 Na₂O, 4.0 P₂O₅, 12.0 K₂O, 5.5 MgO, and 12.5 B₂O₃) has demonstrated favorable processing properties and promising bone regeneration potential. The present study aimed to evaluate the biological effects of the incorporation of highly pro-angiogenic copper (Cu) in 0106-B1-BG in vitro using human bone marrow-derived mesenchymal stromal cells (BMSCs) as well as its in vivo potential for bone regeneration. CuO was added to 0106-B1-BG in exchange for CaO, resulting in Cu-doped BG compositions containing 1.0, 2.5 and 5.0 wt % CuO (composition in wt %: 37.5 SiO₂, 21.6/ 20.1/17.6 CaO, 5.9 Na₂O, 4.0 P₂O₅, 12.0 K₂O, 5.5 MgO, 12.5 B₂O₃, and 1.0/ 2.5/ 5.0 CuO). In vitro, the BGs' impact on the viability, proliferation, and growth patterns of BMSCs was evaluated. Analyses of protein secretion, matrix formation, and gene expression were used for the assessment of the BGs' influence on BMSCs regarding osteogenic differentiation and angiogenic stimulation. The presence of Cu improved cytocompatibility, osteogenic differentiation, and angiogenic response when compared with unmodified 0106-B1-BG in vitro. In vivo, a critical-size femoral defect in rats was filled with scaffolds made from BGs. Bone regeneration was evaluated by micro-computed tomography. Histological analysis was performed to assess bone maturation and angiogenesis. In vivo effects regarding defect closure, presence of osteoclastic cells or vascular structures in the defect were not significantly changed by the addition of Cu compared with undoped 0106-B1-BG scaffolds. Hence, while the in vitro properties of the 0106-B1-BG were significantly improved by the incorporation of Cu, further evaluation of the BG composition is necessary to transfer these effects to an in vivo setting.

Accordingly, caption of Figure 4 “FIGURE 4. (a,b) TEM images at different magnifications and (c) particle size histogram of our sample of GO nanoparticles of GO.” was incorrect.

This should have read “FIGURE 4. TEM image of GO sample”.

We apologize for these errors.

This study aimed to evaluate the properties of radiation cross-linked collagen scaffold (RCS) and its efficacy for alveolar ridge preservation (ARP). RCS was prepared from collagen dispersion by electron beam irradiation and freeze-drying. The microstructure, swelling ratio, area alteration and mechanical properties of RCS were characterized. Fifty-four New Zealand rabbits performing incisor extraction on maxilla and mandible were randomly assigned into positive, sham operation or treatment groups. Micro-computed tomography (micro-CT) scans, performed after 1, 4, and 12 weeks of surgery, were to assess changes in ridge height at buccal and palatal side, in ridge width and in micromorphological parameters. Histological analysis accessed socket microarchitecture. The results showed that RCS had stable mechanical properties and morphologic features that provided a reliable physical support for ARP. Dimensional changes in treatment group revealed significantly greater vertical height at buccal (5.32 [3.37, 7.26] mm, p < .0001) and palatal (4.37 [2.66, 6.09] mm, p < .0001) side, and horizontal width at the maxilla (0.16 [0.04, 0.28] mm, p < .01) and mandible (0.33 [0.11, 0.54] mm, p < .01) than those in sham operation group after 12 weeks. The treatment group had advantage than positive group in vertical height preservation, quantitatively. The order and density of bone trabeculae were improved in treatment group. These findings indicated that RCS had the potential to serve as an effective scaffold for ARP.

When delivering cells on a scaffold to treat a bone defect, the cell seeding technique determines the number and distribution of cells within a scaffold, however the optimal technique has not been established. This study investigated if human adipose-derived stem cells (ASCs) transduced with a lentiviral vector to overexpress bone morphogenetic protein 2 (BMP-2) and loaded on a scaffold using dynamic orbital shaker could reduce the total cell dose required to heal a critical sized bone defect when compared with static seeding. Human ASCs were loaded onto a collagen/biphasic ceramic scaffold using static loading and dynamic orbital shaker techniques, compared with our labs standard loading technique, and implanted into femoral defects of nude rats. Both a low dose and standard dose of transduced cells were evaluated. Outcomes investigated included BMP-2 production, radiographic healing, micro-computerized tomography, histologic assessment, and biomechanical torsional testing. BMP-2 production was higher in the orbital shaker cohort compared with the static seeding cohort. No statistically significant differences were noted in radiographic, histomorphometric, and biomechanical outcomes between the low-dose static and dynamic seeding groups, however the standard-dose static seeding cohort had superior biomechanical properties. The standard-dose 5 million cell dose standard loading cohort had superior maximum torque and torsional stiffness on biomechanical testing. The use of orbital shaker technique was labor intensive and did not provide equivalent biomechanical results with the use of fewer cells.

The physiological mechanism of bone tissue regeneration is intricately organized and involves several cell types, intracellular, and extracellular molecular signaling networks. To overcome the drawbacks of autografts and allografts, a number of synthetically produced scaffolds have been manufactured by integrating ceramics, polymers, and their hybrid-composites. Considering the fact that natural bone is composed primarily of collagen and hydroxyapatite, ceramic-polymer composite materials seem to be the most viable alternative to bone implants. Here, in this experimental study, copolymer PVDF-TrFE has been amalgamated with HA ceramics to produce composite scaffolds as bone implants. In order to fabricate PVDF-TrFE-HA (polyvinylidene fluoride-trifluoroethylene—hydroxyapatite) composite scaffolds, solvent casting-particulate leaching technique was devised. Two scaffold specimens were produced, with different PVDF-TrFE and HA molar ratios (70:30 and 50:50), and then electrically polarized to observe the subsequent polarization impact on the tissue growth and the suppression of bacterial cell proliferation. Both the specimens underwent characterization to analyze their biocompatibility and bactericidal activities. The bacterial culture of Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) bacteria on the composites was studied to understand the antibacterial characteristics. Moreover, MG63 cells cultured on these as-formed composites provided information about osteogenesis. Improved osteogenesis and antibacterial efficacy were observed on both the composites. However, the composite with 70 wt% PVDF-TrFE and 30 wt% HA showed a higher bactericidal effect as well as osteogenesis. It was found that PVDF-TrFE-HA-based biomaterials have the potential for bone tissue engineering applications.

The use of photopolymerization is expanding across a multitude of biomedical applications, from drug delivery to bioprinting. Many of these current and emerging photopolymerization systems employ visible light, as motivated by safety and energy efficiency considerations. However, the “library” of visible light initiators is limited compared with the wealth of options available for UV polymerization. Furthermore, the synthesis of traditional photoinitiators relies on diminishing raw materials, and several traditional photoinitiators are considered emerging environmental contaminants. As such, there has been recent focus on identifying and characterizing biologically sourced, visible light-based photoinitiator systems that can be effectively used in photopolymerization applications. In this regard, several bio-sourced molecules have been shown to act as photoinitiators, primarily through Type II photoinitiation mechanisms. However, whether bio-sourced molecules can also act as effective synergists in these reactions remains unknown. In this study, we evaluated the effectiveness of bio-sourced synergist candidates, with a focus on amino acids, due to their amine functional groups, in combination with two bio-sourced photoinitiator molecules: riboflavin and curcumin. We tested the effectiveness of these photoinitiator systems under both violet (405 nm) and blue (460–475 nm) light using photo-rheology. We found that several synergist candidates, namely lysine, arginine, and histidine, increased the polymerization effectiveness of riboflavin when used with both violet and blue light. With curcumin, we found that almost all tested synergist candidates slightly decreased the polymerization effectiveness compared with curcumin alone under both light sources. These results show that bio-sourced molecules have the potential to be used as synergists with bio-sourced photoinitiators in visible light photopolymerization. However, more work must be done to fully characterize these reactions and to investigate more synergist candidates. Ultimately, this information is expected to expand the range of available visible light-based photoinitiator systems and increase their sustainability.

Translational research in biomaterials and immunoengineering is leading to the development of novel advanced therapeutics to treat diseases such as cancer, autoimmunity, and viral infections. Dendritic cells (DCs) are at the center of these therapeutics given that they bridge innate and adaptive immunity. The biomaterial system developed herein uses a hydrogel carrier to deliver immunomodulatory DCs for amelioration of autoimmunity. This biomaterial vehicle is comprised of a poly (ethylene glycol)-4 arm maleimide (PEG-4MAL) hydrogels, conjugated with the immunosuppressive cytokine, interleukin-10, IL-10, and cross-linked with a collagenase-degradable peptide sequence for the injectable delivery of immunosuppressive DCs to an anatomical disease-relevant site of the cervical lymph nodes, for intended application to treat multiple sclerosis. The amount of IL-10 incorporated in the hydrogel was optimized to be 500 ng in vitro, based on immunological endpoints. At this concentration, DCs exhibited the best viability, most immunosuppressive phenotype, and protection against proinflammatory insult as compared with hydrogel-incorporated DCs with lower IL-10 loading amounts. Additionally, the effect of the degradability of the PEG-4MAL hydrogel on the release rate of incorporated IL-10 was assessed by varying the ratio of degradable peptides: VPM (degradable) and DTT (nondegradable) and measuring the IL-10 release rates. This IL-10-conjugated hydrogel delivery system for immunosuppressive DCs is set to be assessed for in vivo functionality as the immunosuppressive cytokine provides a tolerogenic environment that keeps DCs in their immature phenotype, which consequently enhances cell viability and optimizes the system's immunomodulatory functionality.