Journal of Materials Science: Materials in Medicine

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Online ISSN: 1573-4838
Print ISSN: 0957-4530
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The instruments for testing radial force (A), trackability (B), stent dislodgment bench test (C)
Crossing profile analysis result (A) and folding shape (B) of D + Storm® DES (Drug eluting stent) (a), Synergy™ (b), Orsiro® (c), and Xience sierra™ (d)
Mechanical properties of D + Storm® DES (Drug-eluting stent) (a), Synergy™ (b), Orsiro® (c), and Xience sierra™ (d). A Foreshortening, B Recoil, C Radial force analysis
Trackability (A) and dislodgement force test (B) of D + Storm® DES (Drug-eluting stent) (a), Synergy™ (b), Orsiro® (c), and Xience sierra™ (d)
The purpose of this study was to evaluate the performance of biodegradable polymer sirolimus and ascorbic acid eluting stent systems with four commercially available drug-eluting stents (DES). We investigated the characterization of mechanical properties by dimension, foreshortening, recoil, radial force, crossing profile, folding shape, trackability, and dislodgement force. Additionally, we identify the safety and efficacy evaluation through registry experiments. Each foreshortening and recoil of D + Storm® DES is 1.3 and 3.70%, which has better performance than other products. A post-marketing clinical study to evaluate the performance and safety of D + Storm® DES is ongoing in real-world clinical settings. Two hundred one patients were enrolled in this study and have now completed follow-up for up to 1 month. No major adverse cardiovascular event (MACE) occurred in any subjects, confirming the safety of D + Storm® DES in the clinical setting. An additional approximately 100 subjects will be enrolled in the study and the final safety profile will be assessed in 300 patients. In conclusion, this study reported the objective evaluation of DES performance and compared the mechanical responses of four types of DES available in the market. There is little difference between the four cardiovascular stents in terms of mechanical features, and it can help choose the most suitable stent in a specific clinical situation if those features are understood. Graphical abstract
Fractures of the paranasal sinuses often require surgical intervention. Persisting bone defects lead to permanent visible deformities of the facial contours. Bone substitutes for reconstruction of defects with simultaneous induction of new bone formation are not commercially available for the paranasal sinus. New materials are urgently needed and have to be tested in their future area of application. For this purpose critical size defect models for the paranasal sinus have to be developed. A ≥2.4 cm large bilateral circular defect was created in the anterior wall of the maxillary sinus in six sheep via an extraoral approach. The defect was filled with two types of an osteoconductive titanium scaffold (empty scaffold vs. scaffold filled with a calcium phosphate bone cement paste) or covered with a titanium mesh either. Sheep were euthanized after four months. All animals performed well, no postoperative complications occured. Meshes and scaffolds were safely covered with soft tissue at the end of the study. The initial defect size of ≥2.4 cm only shrunk minimally during the investigation period confirming a critical size defect. No ingrowth of bone into any of the scaffolds was observed. The anterior wall of the maxillary sinus is a region with low complication rate for performing critical size defect experiments in sheep. We recommend this region for experiments with future scaffold materials whose intended use is not only limited to the paranasal sinus, as the defect is challenging even for bone graft substitutes with proven osteoconductivity. Graphical abstract
Characterization of TBC, DBM, TBC&BMP-2 and DBM&BMP-2. A The photographs of TBC, DBM, TBC&BMP-2 and DBM&BMP-2; B The maximum compressive, n = 5; C The yield strength, n = 5; D SEM images of TBC, DBM, TBC&BMP-2 and DBM&BMP-2, 100×; E The relative cells growth rate (RGR), n = 5; F The release of BMP-2, n = 3. *P < 0.05
The repair of femoral condyle defect. A HE staining of 4 weeks; B HE staining of 8 weeks; C Micro-CT scanning of 8 weeks, n = 6; D The bone mass/total volume (BV/TV) scores, n = 6; E The bone trabecular thickness (TT), n = 6. *P < 0.05
The repair of radial defect. A HE staining of 4 weeks; B HE staining of 8 weeks; C Calcein staining of 8 weeks, n = 3; D The mineralization and deposition rate, n = 6; E The X-ray films of 8 weeks, n = 6; F The X-ray scoring, n = 6; G The peak load, n = 6; H The maximum deflection, n = 6. *P < 0.05
Xenograft bone scaffolds have certain advantages such as mechanical strength, osteoinductive properties, sufficient source and safety. This study aimed to compare osteogenesis of the two main bovine bone xenografts namely true bone ceramics (TBC) and decalcified bone matrix (DBM), and TBC or DBM combined with bone morphogenetic protein (BMP)-2 (TBC&BMP-2 and DBM&BMP-2). The characteristics of TBC and DBM were investigated by observing the appearance and scanning electron microscopic images, examining mechanical strength, evaluating cytotoxicity and detecting BMP-2 release after being combined with BMP-2 in vitro. The femoral condyle defect and radial defect models were successively established to evaluate the performance of the proposed scaffolds in repairing cortical and cancellous bone defects. General observation, hematoxylin and eosin (HE) staining, mirco-CT scanning, calcein double labeling, X-ray film observation, three-point bending test in vivo were then performed. It indicated that the repair with xenograft bone scaffolds of 8 weeks were needed and the repair results were better than those of 4 weeks whatever the type of defects. To femoral condyle defect, TBC and TBC&BMP-2 were better than DBM and DBM&BMP-2, and TBC&BMP-2 was better than TBC alone; to radial defect, DBM and DBM&BMP-2 were better than TBC and TBC&BMP-2, and DBM&BMP-2 was better than DBM alone. This study has shown that TBC and DBM xenograft scaffolds can be more suitable for the repair of cancellous bone and cortical bone defects for 8 weeks in rats, respectively. We also have exhibited the use of BMP-2 in combination with DBM or TBC provides the possibility to treat bone defects more effectively. We thus believe that we probably need to select the more suitable scaffold according to bone defect types, and both TBC and DBM are promising xenograft materials for bone tissue engineering and regenerative medicine. Graphical abstract
a Schematic illustration showing scaffold preparation processes; b FTIR spectra; c TGA curves; d compressive stress–strain curves of pristine scaffold and Mn-incorporated scaffold; e SEM images of the scaffold; f macroscopic image of the scaffold and EDS images of Mn, C, and O elements
Biological assessment in vitro. a Schematic illustration showing chondrocyte isolation and culture processes; b confocal laser scanning microscopy of chondrocytes; c live/dead assay of chondrocytes on the scaffolds, live cells (green), dead cells (red) and HE stain at different concentration of Mn²⁺ after 3 days (bar = 200 μm); d, e schematic diagram and photographs of chondrocyte proliferation on day 3; f live cells (green) at 0.5 μg/mL Mn²⁺ concentration after 10 days and 4 weeks (bar = 100 μm); g, h expression of Sox9, Col II, and aggrecan genes by real-time PCR on days 1, 3, and 5 after incubation with pristine or Mn-incorporated scaffolds. (*p < 0.05 compared with the control group)
a Immunofluorescence and IHC staining images of integrin in chondrocytes co-cultured with the scaffold for 3 days; b representative immunofluorescence staining of Col II (red): actin cytoskeletons (green) and nuclei (blue) in chondrocytes co-cultured with the scaffold for 3 days; c western blot analysis of Mn ion-induced activation of the AKT/p-AKT and ERK/p-ERK pathways in chondrocytes
a Schematic diagram of osteochondral repair and histological analysis procedure in vivo; b The Operation of osteochondral defect in rats; c Histological analysis was performed by HE, Toluidine blue, and Col II staining
Schematic of the scaffold preparation and loading of cells onto a previously fabricated scaffold for treating rat articular defects
Cartilage is an alymphatic, avascular and non-innervated tissue. Lack of potential regenerative capacity to reconstruct chondral defect has accelerated investigation and development of new strategy for cartilage repair. We prepared a manganese ion-incorporated natupolymer-based scaffold with chitosan-gelatin by freeze-drying procedure. The scaffold was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, energy dispersive spectroscopy, compressive testing, and analysis of porosity and flexibility. Live/dead assay confirmed the good cytocompatibility of prepared scaffold on rat articular chondrocytes after 10 days and 4 weeks of culture. The manganese-loaded composite scaffold upregulated the expression of chondrogenic-related markers (Sox9, integrin, and Col II) in chondrocytes. Western blot analysis of proteins extracted from chondrocytes grown on scaffolds indicated the signaling pathways of p-Akt and p-ERK1/2 played a key role. Histological analysis following implantation of current composite scaffold loaded with chondrocytes into a rat articular cartilage defect model showed that the scaffolds promoted the formation of collagen II and cartilage repair. These findings suggested the potential of manganese-loaded scaffold to promote new cartilage formation and a promising strategy for articular cartilage engineering application.
Although titanium (Ti) and Ti-based alloy have been widely used as dental and orthopedic implant materials, its bioinertness hindered the rapid osseointegration. Therefore, it is recommended to acquire ideal topographic and chemical characteristics through surface modification methods. 3D printing is a delicate manufacture technique which possesses superior controllability and reproducibility. While aspirin serve as a well-established non-steroidal anti-inflammatory agent. Recently, the importance of immune system in regulating bone dynamics has attracted increasing attention. We herein superimposed the aspirin/poly (lactic–co–glycolic acid) (ASP/PLGA) coating on the 3D-printed Ti-6Al-4V surface with uniform micro-structure to establish the Ti64-M-ASP/PLGA substrate. Scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and contact angle test confirmed the successful fabrication of the Ti64-M-ASP/PLGA substrate, with increased wettability and sustained release pattern of ASP. Compared with the Ti64 base material, the Ti64-M-ASP/PLGA substrate showed enhanced M2 and depressed M1 genes and proteins expressions in macrophages. The novel Ti64-M-ASP/PLGA substrate also displayed enhanced osteoblast proliferation, adhesion, extracellular mineralization ability and osteogenic gene expressions when cultured with macrophage conditioned medium in vitro. Furthermore, rat femora implantation model was used for in vivo evaluation. After 4 weeks of implantation, push out test, micro-computed tomography (micro-CT) and histological analyses all confirmed the superior osseointegration capabilities of the Ti64-M-ASP/PLGA implant than the other groups. Our study revealed the synergistic role played by 3D-printed micro topography and immunoregulatory drug aspirin in promoting osteogenesis in vitro and accelerating osseointegration in vivo, thus providing a promising method for better modifying the implant surface. Graphical abstract
Hepatocellular carcinoma is a common type of cancer associated with a high mortality rate. Among several bioactive compounds, Murrayafoline A (MuA) has been proved as a bio substance that exhibits great potentials in treating liver cancer. In order to overcome the high cytotoxicity and low solubility of MuA, a delivery system based on nanocarriers is necessary to deliver MuA towards the desired target. In the present study, 18β-glycyrrhetinic acid (GA), which is known as a ligand for liver targeting, was used to construct the cholesterol-poly (ethylene glycol)-glycyrrhetinic acid (GA-PEG-Chol) conjugate and liposome for MuA administration. The compound was then examined for therapeutic efficacy and safety in HUVEC and HepG2 cells in 2D and 3D cell cultures. Results have shown that MuA-loaded liposomes had IC 50 value of 2 µM in HepG2 and had the cytosolic absorption of 8.83 ± 0.97 ng/10 ⁵ cells, while The IC50 value of MuA-loaded liposomes in HUVEC cell lines was 15 µM and the the cytosolic absorption was recorded as 3.62 ± 0.61 cells. The drug test on the 3D cancer sphere platform of the HepG2 cancer sphere showed that MuA-loaded GA liposomes had the highest efficacy at a concentration of 100 µg/mL. In short, these results suggest that MuA-loaded GA liposomes have the potential for maintenance drug delivery and liver targeting.
Bone defects still pose various challenges in osteology. As one treatment method for bone defects, tissue engineering requires biomaterials with good biocompatibility and stem cells with good differentiation. This study aimed to fabricate a 3D-printed polylactic acid and hydroxyapatite (PLA/HA) composite scaffold with urine-derived stem cells (USCs) to study its therapeutic effect in a rat model of skull defects. USCs were isolated and extracted from the urine of healthy adult males and inoculated onto PLA/HA and PLA scaffolds fabricated by 3D printing technology. A total of 36 skull defect models in eighteen Sprague–Dawley rats were randomly divided into a control group (no treatment of the defects), PLA group (treated with PLA scaffolds with USCs), and PLA/HA group (treated with PLA/HA scaffolds with USCs). The therapeutic efficacy was evaluated by real-time PCR, microcomputed tomography (micro-CT), and immunohistochemistry at 4, 8, and 12 weeks. We found that the PLA/HA scaffold loaded with USCs effectively promoted new bone regeneration in the defect area. CT images showed that in the PLA/HA group, the defect area was almost entirely covered by newly formed bone (coverage of 96.7 ± 1.6%), and the coverage was greater than that in the PLA group (coverage of 74.6 ± 1.9%) at 12 weeks. Histology and immunohistochemical staining showed the highest new bone formation on the PLA/HA scaffolds containing USCs in the defect site at 12 weeks. These findings demonstrate the broad application prospects of PLA/HA scaffolds with USCs in bone tissue engineering. Graphical abstract
Repeat firing produces uncertainty about stabilizing lithium disilicate glass-ceramic (LDGC) material properties, even though prolonged holding time can enhance the mechanical property of LDGC during a single firing cycle. However, the effect of prolonged holding time and repeat firing on the mechanical property and microstructure of LDGC is not fully understood. In the present study, three groups of LDGC material were created: (i) extension of holding time (7 vs. 14 vs. 28 min) at 780–800 °C; (ii) holding time extension (7 vs. 14 min) and dual sintering at 800–820 °C, respectively; (iii) dual sintering with prolonged holding time (7 vs. 14 min) at 820–840 °C. The nano-indenter test revealed that prolonged holding time (14 and 28 min) promoted the enhancement of LDGC hardness and Young’s modulus. X-ray photoelectron spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy confirmed that prolonged holding time increased and stabilized LD phase in LDGC, as well as induced residual compressive stress. Scanning electron microscopy showed that prolonged holding time increased LD crystal grains homogeneously and facilitated LDGC to form dense interlocking structure without enlarging crystal size grains significantly. In contrast, LDGC that dual sintered alone at 820–840 °C possessed inferior mechanical properties, coupled with heterogeneous crystal phases, residual tensile stress, and melted crystals grains in the porous microstructure. Interestingly, these deteriorated properties of LDGC caused by dual sintering alone could be counteracted by prolonging the holding time. Nevertheless, the LDGC materials displayed an excellent biocompatibility throughout the study. This study identified that prolonged holding time during repeated firing cycles stabilized LD phase and crystal grain size of LDGC, thus enhanced the mechanical properties, which provided a new insight to extend the repeat fired restoration longevity of LDGC. Graphical abstract
Two heat treatments were carried out at below (Ti6Al4V800) and above (Ti6Al4V1050) the beta-phase transformation temperature (TTRANSUS = 980 °C), to study the effect of microstructural changes on osseointegration. The alloys were implanted in the femurs of hind legs of Wistar rats for 15, 30, and 60 days. Histology of the femur sections obtained for the first 15 days showed inflammatory tissue surrounding the implants and tissue contraction, which prevented osseointegration in early stages. After 30 days, trabecular bone, reduction of inflammatory tissue around the implants, and osseointegration were observed in Ti6Al4V as received and Ti6Al4V1050 alloys, while osseointegration was detected for the three alloys after 60 days. These results were supported through morphometric studies based on the analysis of Bone Implant Contact (BIC), where there was a larger bone contact after 60 days for the Ti6Al4V1050 alloy; indicating that microstructural features of the Ti6Al4V alloys influence their osseointegration, with the lamellar microstructure (Ti6Al4V1050), being the most responsive. Graphical abstract
There are no suitable methods to develop the small-calibre tissue-engineered blood vessels (TEBVs) that can be widely used in the clinic. In this study, we developed a new method that combines electrospinning and in-body tissue architecture(iBTA) to develop small-calibre TEBVs. Electrospinning imparted mechanical properties to the TEBVs, and the iBTA imparted biological properties to the TEBVs. The hybrid fibres of PLCL (poly(L-lactic-co-ε-caprolactone) and PU (Polyurethane) were obtained by electrospinning, and the fibre scaffolds were then implanted subcutaneously in the abdominal area of the rabbit (as an in vivo bioreactor). The biotubes were harvested after four weeks. The mechanical properties of the biotubes were most similar to those of the native rabbit aorta. Biotubes and the PLCL/PU vascular scaffolds were implanted into the rabbit carotid artery. The biotube exhibited a better patency rate and certain remodelling ability in the rabbit model, which indicated the potential use of this hybridization method to develop small-calibre TEBVs. Sketch map of developing the biotube. The vascular scaffolds were prepared by electrospinning (A). Silicone tube was used as the core, and the vascular scaffold was used as the shell (B). The vascular scaffold and silicone tube were implanted subcutaneously in the abdominal area of the rabbit (C). The biotube was extruded from the silicone tube after 4 weeks ofembedding (D). The biotube was implanted for the rabbit carotid artery (E).
Percutaneous implants are frequently affected by bacterial growth at the skin-implant interface. Integration between implant and surrounding skin is important to prevent bacteria from spreading to the underlying tissue. The standard method to evaluate skin-implant integration is by histomorphometry on samples which have been placed in tissue grown in vivo or ex vivo. In this study, a biomechanical method was developed and evaluated. The integration of implants into porcine skin was studied in an ex vivo model, where pig skin samples were cultivated in a nutrient solution. Cylindrical shaped implants, consisting of polyether ether ketone (PEEK) and titanium (Ti) with different surface treatments, were implanted in the skin tissue and the skin was grown in nutrient solution for 2 weeks. The implants were then extracted from the implantation site and the mechanical force during extraction was measured as a quantitative assessment of skin-implant integration. Implants from each group were also processed for histomorphometry and the degree of epidermal downgrowth (ED) and tissue to implant contact (TIC) was measured. A higher mean pullout force was observed for the PEEK implants compared to the Ti implants. Applying nanosized hydroxyapatite (HA) on Ti and PEEK increased the pullout force compared to uncoated controls, 24% for machined and 70% for blasted Ti, and 51% for machined PEEK. Treatment of Ti and PEEK with nanosized zirconium phosphate (ZrP) did not increase the pullout force. The histomorphometry analysis showed correlation between ED and pullout force, where the pullout force was inversely proportional to ED. For TIC, no significant differences were observed between the groups of same material (i.e. Ti, Ti+HA, Ti+ZrP, and PEEK, PEEK + HA, PEEK + ZrP), but it was significantly higher for PEEK compared to Ti. Scanning electron microscopy analysis was done on samples before and after the pullout tests, showing that the ZrP coating was unaffected by the 2 week ex vivo implantation and pullout procedure, no dissolution or detachment of the coating was observed. For the HA coating, a loss of coating was seen on approximately 5% of the total surface area of the implant. Graphical abstract
Polydimethylsiloxane (PDMS) is a commonly used insulation/packaging material for implantable neural electrodes. Nevertheless, the PDMS-initiated tissue response would lead to the deterioration of the electrode performances post-implantation, owing to its intrinsic hydrophobic and cell-repellent surface. The conventional physical coatings by hydrophilic hydrogels or bioactive molecules are unable to maintain during the long-term implantation due to their low stability by physical adhesion. In this work, we first anchor both hydrophilic polyethylene glycol (PEG) and bioactive molecule poly-L-lysine (PLL) on the PDMS surface by chemical coupling to change the PDMS surface from hydrophobic and cell-repellent to hydrophilic and cell-adhesive. XPS tests indicate the chemically coupled modification layers are stable on the PDMS surface after experiencing a harsh rinse process. Contact angle measurements show that the use of PEG 600 with the moderate molecular weight results in the highest hydrophilicity for the resulting PDMS-PEG-PLL. PC12 cell evaluation results exhibit that the PDMS-PEG-PLL with PEG 600 leads to significantly larger cell adhesion area, more neurite number, and longer neurite length than the PDMS. The PDMS-PEG-PLL with PEG 600 featuring stable modification layers, high hydrophilicity, and superior cell affinity has great potential in stabilizing the neural electrode-tissue interface for the long-term implantation. Graphical abstract
Chitosan coatings have shown good bioactive properties such as antibacterial and antiplatelet properties, especially on blood-contacted biomedical materials. However, as blood-contacted biomedical device, the intravascular metal stent has a burden with adverse effects on the structural integrity, such as mechanical load during implantation and substrate degradation if a biodegradable metal is used as the substrate. It is unquestionably true that the structural integrity of the coated stent is essential. The adhesion strength between the coating and the substrate positively affects it. Silane and polydopamine (PDA) interstitial layers have been investigated to improve the corrosion resistance, biosafety and adhesion strength. This work addressed this challenge by using PDA as an intermediate and glutaraldehyde as a linking agent to establish a strong link between the polymer coating and the intermediate coating. Compared with PDA-only and glutaraldehyde-linked silane layer, the novel coating displayed a notable increase in adhesion. When compared with the bare Ni-free stainless steel, the performance of the novel coating was not significantly different. This novel chitosan film on the glutaraldehyde linked-PDA interface can be applied to various metallic substrates where synergic bioactive and anticorrosive effects of PDA interstitial coating and chitosan are needed. Graphical abstract
The design process of 3D porous scaffold. A CT scan images of the femoral shaft with PMMA spacer; B 3D reconstruction was performed based upon CT scan; C the suitable scaffold model design and its fixation by intramedullary nail was realized by means of medical-industrial interactive platform; D the distal side of the scaffold was fixed by locking screws and lateral wing structure
The therapeutic process of the first typical case. A, B The initial X-ray displayed the patient suffered the distal femoral displaced fracture; C–E The patient underwent the surgical treatment, and at 13 months after the initial surgery, X-ray and CT scan showed fracture nonunion and ends sclerosis, meanwhile, the plate had broken; F we cleared the sequestrums and filled a PMMA spacer into the femoral defect with 9.5 cm length, and stabilized the femur by external fixator; G–J after a 10-week interval, the bone defect was repaired by a customized 3D printed scaffold, and the postoperative regular X-rays showed the scaffold kept stable and new bone grew gradually on the surface of scaffold from both ends of the defect (as displayed in the red boxes)
The therapeutic process of the second typical case. A, B The initial X-ray displayed the patient suffered the tibial comminuted fracture; C–E the patient underwent the surgical treatment, and at 10 months after the initial surgery, X-ray and CT scan showed fracture nonunion and sequestrums; F we cleared the sequestrums and filled a PMMA spacer into the femoral defect with 6.3 cm length, and stabilized the femur by external fixator; G–L after an 8-week interval, the bone defect was repaired by a customized 3D printed scaffold, and the postoperative regular X-rays also showed the scaffold kept stable and new bone grew gradually on the surface of scaffold from both ends of the defect (as displayed in the red boxes)
The lower limb function of the second typical case at the last follow-up. As displayed, his loading and motion function of both legs were satisfactory. A Stand, B Crouch, C Bend leg, and D Straight leg
The repair of critical diaphyseal defects of lower weight-bearing limbs is an intractable problem in clinical practice. From December 2017, we prospectively applied 3D printed porous Ti6Al4V scaffolds to reconstruct this kind of bone defect. All patients experienced a two-stage surgical process, including thorough debridement and scaffold implantation. With an average follow-up of 23.0 months, ten patients with 11 parts of bone defects were enrolled in this study. The case series included three females and seven males, their defect reasons included seven parts of osteomyelitis and four parts of aseptic nonunion. The bone defects located at femur (five parts) and tibia (six parts), with an average defect distance of 12.2 cm. Serial postoperative radiologic follow-ups displayed a continuous process of new bone growing and remodeling around the scaffold. One patient suffered tibial varus deformity, and he underwent a revision surgery. The other nine patients achieved scaffold stability. No scaffold breakage occurred. In conclusion, the implantation of 3D printed Ti6Al4V scaffold was feasible and effective to reconstruct critical bone defects of lower limbs without additional bone grafting. Graphical abstract
Current evidence has suggested that diabetes increases the risk of implanting failure, and therefore, appropriate surface modification of dental implants in patients with diabetes is crucial. TiO2 nanotube (TNT) has an osteogenic nanotopography, and its osteogenic properties can be further improved by loading appropriate drugs. Cinnamaldehyde (CIN) has been proven to have osteogenic, anti-inflammatory, and anti-bacterial effects. We fabricated a pH-responsive cinnamaldehyde-TiO2 nanotube coating (TNT-CIN) and hypothesized that this coating will exert osteogenic, anti-inflammatory, and anti-bacterial functions in a simulated diabetes condition. TNT-CIN was constructed by anodic oxidation, hydroxylation, silylation, and Schiff base reaction to bind CIN, and its surface characteristics were determined. Conditions of diabetes and diabetes with a concurrent infection were simulated using 22-mM glucose without and with 1-μg/mL lipopolysaccharide, respectively. The viability and osteogenic differentiation of bone marrow mesenchymal stem cells, polarization and secretion of macrophages, and resistance to Porphyromonas gingivalis and Streptococcus mutans were evaluated. CIN was bound to the TNT surface successfully and released better in low pH condition. TNT-CIN showed better osteogenic and anti-inflammatory effects and superior bacterial resistance than TNT in a simulated diabetes condition. These findings indicated that TNT-CIN is a promising, multifunctional surface coating for patients with diabetes needing dental implants. Graphical abstract
The purpose of this study is to investigate the role of Silibinin (SIL)-modified Hydroxyapatite coating on osseointegration in diabetes in vivo and in vitro and explore the mechanism of osteogenic differentiation of MC3T3-E1. RT-qPCR, Immunofluorescence, and Western blot were used to measure the expression level of oxidative Stress Indicators and osteogenic markers proteins. Moreover, CCK-8 assay was conducted to detect cell viability in hyperglycemia. Alizarin red staining and alkaline phosphatase staining were used to examine osteogenic function and calcium deposits. The diabetic rat model receive titanium rod implantation was set up successfully and Von-Gieson staining was used to examine femoral bone tissue around titanium rod. Our results showed that intracellular oxidative stress in hyperglycemia was overexpressed, while FoxO1, SIRT1, GPX1, and SOD2 were downregulated. SIL suppressed oxidative stress to promote osteogenic differentiation. Additionally, it was confirmed that SIL promoted osteogenic differentiation of MC3T3-E1 and obviously restored the osseointegration ability of diabetic rats. Further study indicated that SIL exerted its beneficial function through activation SIRT1/SOD2 signaling pathway to restore osteoblast function, and improved the osseointegration and stability of titanium rods in vivo. Our research suggested that the SIL-modulated oxidative Stress inhibition is responsible for the activation of the process of osteogenic differentiation through activation SIRT1/SOD2 signaling pathway in hyperglycemia, providing a novel insight into improving prosthetic osseointegration in diabetic patients.
Bone graft materials are applied in patients to augment bone defects and enable the insertion of an implant in its ideal position. However, the currently available augmentation materials do not meet the requirements of being completely resorbed and replaced by new bone within 3 to 6 months. A novel electrospun cotton-wool like material (Bonewool®, Zurich Biomaterials LLC, Zurich, Switzerland) consisting of biodegradable poly(lactic-co-glycolic) acid (PLGA) fibers with incorporated amorphous ß-tricalcium phosphate (ß-TCP) nanoparticles has been compared to a frequently used bovine derived hydroxyapatite (Bio-Oss®, Geistlich Pharma, Wolhusen, Switzerland) in vitro. The material composition was determined and the degradation behavior (calcium release and pH in different solutions) as well as bioactivity has been measured. Degradation behavior of PLGA/ß-TCP was generally more progressive than for Bio-Oss®, indicating that this material is potentially completely resorbable. Graphical abstract
Background Diabetic wound is a severe complication of diabetes. Stem cell is considered as a promising therapy for diabetic skin wounds. Hydrogel can supply niche for cells adhesion and survival to improve the efficacy of stem cell therapy, but the development of hydrogel with suitable properties remains a great challenge. Thus, our study was conducted to combine an optimized hydrogel with stem cell to improve complex diabetic wound treatment. Methods This study constructed a hydrogel with low toxicity and adjustable mechanical properties from gelatin methacrylate (GelMA) and chitosan-catechol (Chi-C), and encapsulated human umbilical cord-mesenchymal stem cells (hUMSCs) to repair full-thickness diabetic wound. Results We explored the relationship between mechanical stiffness and cell proliferation and differentiation potency, and found 10% GelMA hydrogel with an optimal stiffness improved hUMSCs adhesion, proliferation, and differentiation potency maintenance in vitro. Assistant with optimized hydrogel encapsulating hUMSCs, diabetic wound healing process was greatly accelerated, including accelerated wound closure, inhibited secretion of inflammatory factors TNF-α and IL-1β, promoted vascular regeneration and collagen deposition after treatment of hUMSCs. Conclusions The optimized hydrogel encapsulating hUMSCs improved diabetic wound healing, and has a broad implication for the treatment of diabetic complication.
We mainly proceed from the view of biological effect to study the acellular bovine bone matrix (ABBM) by the low concentration of hydrogen oxidation. After cleaning the bovine bone routinely, it was cleaned with different concentrations of NaOH and stained with hematoxylin-eosin (HE) to observe the effect of decellulization. The effect of bovine bone matrix treated with NaOH were observed by optical microscopy and scanning electron microscopy (SEM), and compared by DNA residue detection. Cell toxicity was also evaluated in MC3T3-E1 cells by CCK-8. For the in vitro osteogenesis detection, alkaline phosphatase (ALP) staining and alizarin red (AR) staining were performed in MC3T3-E1 cells. And the in vivo experiment, Micro CT, HE and Masson staining were used to observe whether the osteogenic effect of the materials treated with 1% NaOH solution was affected at 6 and 12 weeks. After the bovine bone was decellularized with different concentrations of NaOH solution, HE staining showed that ultrasonic cleaning with 1% NaOH solution for 30 min had the best effect of decellularization. The SEM showed that ABBM treated with 1% NaOH solution had few residual cells on the surface of the three-dimensional porous compared to ABBM treated with conventional chemical reagents. DNA residues and cytotoxicity of ABBM treated with 1% NaOH were both reduced. The results of ALP staining and AR staining showed that ABBM treated with 1% NaOH solution had no effect on the osteogenesis effect. The results of micro-CT, HE staining and Masson staining in animal experiments also showed that ABBM treated with 1% NaOH solution had no effect on the osteogenesis ability. The decellularization treatment of ABBM with the low concentration of NaOH can be more cost-effective, effectively remove the residual cellular components, without affecting the osteogenic ability. Our work may provide a novelty thought and a modified method to applicate the acellular bovine bone matrix clinically better.
Hyperbaric oxygen therapy (HBOT) has beneficial effects for patients complaining of poor bone healing such as related to diabetes mellitus. However, it is known that changing pressure conditions might cause dental barotrauma in the oral cavity. The aim of this study was to evaluate implant mechanical stability under HBOT pressure. Thirty-five implants were placed in bone blocks divided into five groups as control, 1, 3, 5, 7 HBOT cycles. In one cycle, 2.4 bar 100% oxygen pressure was performed. Implants’ stabilities were measured with resonance frequency analysis (RFA) and removal torque (RT) meter device. Data were analyzed using Shapiro Wilk, ANOVA, and Tukey HSD tests for RFA and RT values considering p < 0.05 as the statistical significance level. RFA and RT values were compared by Pearson correlation coefficiency. RFA values of 5 and 7 HBOT cycles were significantly lower than 1, 3 HBOT and control group (p < 0.001). There was no statistical difference between 5 and 7 HBOT cycles RFA values. HBOT pressure simulation slightly but statistically decreased the stability for the implants exposed to 5 and 7 HBOT cycles. Graphical abstract
SEM images with the magnifications of (I) ×10,000 and (II) ×80,000 for the samples of (a) PT, (b) SLA, (c) SLA-Ag-I, (d) SLA-Ag-II, and (e) SLA-Ag-III. Pictures with a low magnification (×10,000) show the overall microscale topography, while those with a high magnification (×80,000) demonstrate the existence of nanoparticles
XPS results of four experimental groups (SLA, SLA-Ag-I, SLA-Ag-II, and SLA-Ag-III). a Wide scan XPS spectra. b XPS depth-profile of four groups. Detailed spectra of (c) Ag 3d and (d) Ti 2p detected on (i) SLA, (ii) SLA-Ag-I, (iii) SLA-Ag-II, and (iv) SLA-Ag-III surfaces
a Photographs of re-cultivated E. coli and S. aureus collected from the samples. Antibacterial ratio against E. coli (b) and S. aureus (c)
Viabilities of E. coli (a) and S. aureus (b) cultured on the samples. Fluorescence images of the live/dead-stained E. coli (c) and S. aureus (d) cultured on the samples
SEM images showing the E. coli (a) and S. aureus (b) cultures on various samples
Antibacterial activity is one of the most vital characteristics for Titanium (Ti) dental implants. Coating antibacterial material onto Ti surfaces is an effective approach to enhance their intrinsic antibacterial ability. However, a cost-effective but efficient coating strategy for realizing this objective still remains challenging. In this study, we proposed a novel implant surface modification strategy for coating silver nanoparticles onto the porous Ti surface via a facile electron beam evaporation (EBE) approach. Porous Ti surfaces were firstly prepared by sand-blasting large grit acid-etching (SLA) process. Then, the silver nanoparticles coating thickness on the porous Ti surface was adjusted and optimized by altering the duration of EBE process. Consequently, composite porous Ti surfaces with different silver thicknesses were synthesized. Polished Ti (PT) surface without SLA or EBE process was also prepared as the controlled blank group. The surface characterizations were analyzed by SEM, AFM, and XPS. After that, the antibacterial properties of all groups were tested with bacteria counting method, bacterial viability test, live/dead bacterial staining, and SEM examination. Results show that silver nanoparticles were uniformly distributed on the porous Ti surfaces after the SLA and EBE processes. After being incorporated with silver nanoparticles, the composite surfaces successfully inhibited the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The antibacterial ratio (AR) values of SLA-Ag groups increased with the increasing silver thickness and are significantly higher than those of PT and SLA groups. Therefore, by the SLA and EBE processes, the composite porous Ti surfaces modified with silver nanoparticles coatings demonstrate superior antibacterial property compared with pure Ti surfaces, which is highly promising for enhancing the antibacterial functions of dental implants. Graphical abstract
The aim of this study was to evaluate the effects of butt margin, occlusal thickness and pulp chamber extension depth on stress distributions on mandibular molar endodontically treated teeth (ETT) with EMAX endocrown restoration using 3-dimensional finite element analysis (FEA). The FEA models of endocrown with flat surface or curve surface of butt margin were firstly evaluated stress distributions, and then 9 FEA models of endocrown with 1-, 2- or 3-mm pulp chamber extension depth and 1-, 2- or 3-mm occlusal thickness were generated using curve surface of butt margin. In all of FEA models, a 200 N of vertical load or horizontal load was applied, and the von Mises stress (VMS) were evaluated. The results showed that curve surface of butt margin offered more adhesive area of enamel, though VMS on the prepared teeth was similar in flat surface and curve surface models. In 9 endocrown models, 2-mm occlusal thickness showed the lowest VMS on restorations, teeth tissue and root furcations, and 2-mm extension depth displayed the lowest VMS on root furcations under vertical load. Also, 2-mm extension depth exhibited the lowest VMS on restorations and teeth tissue under horizontal load. Within the limitations of this FEA study, the results of this study could be used as an aid for dentists to better devise endocrown restorations. Graphical abstract
Stem cells exist as normal cells in embryonic and adult tissues. In recent years, scientists have spared efforts to determine the role of stem cells in treating many diseases. Stem cells can self-regenerate and transform into some somatic cells. They would also have a special position in the future in various clinical fields, drug discovery, and other scientific research. Accordingly, the detection of safe and low-cost methods to obtain such cells is one of the main objectives of research. Jaw, face, and mouth tissues are the rich sources of stem cells, which more accessible than other stem cells, so stem cell and tissue engineering treatments in dentistry have received much clinical attention in recent years. This review study examines three essential elements of tissue engineering in dentistry and clinical practice, including stem cells derived from the intra- and extra-oral sources, growth factors, and scaffolds.
Radiographs taken before index revision surgery, i.e., bone marrow sample extraction (donors 1–6, low-centered ap pelvis; donors 7 & 8, lateral knee view). Blue asterisks indicate the respective index joint. Donor 1–2, modular short stem total hip arthroplasty; donor 3–6, hip resurfacing implant; donor 7–8, total knee arthroplasty
Representative workflow for data processing of the nano-XRF map of periprosthetic bone marrow from a patient with hip resurfacing implant. a, b Linear scale and log scale maps of the spatial Co signals. c Linear scale map of the spatial Co signal following top-hat transformation. d Map indicating all signals equal and greater than the derived Co signal threshold. e Connected component labeling indicating all particles included for the subsequent analyses of (f) particle size, number and elemental composition
Exposure to CoCrMo particles in periprosthetic bone marrow samples from three patients undergoing revision surgery of a total knee arthroplasty implant (TKA), a modular hip arthroplasty implant with modular femoral component (mTHA) and a hip resurfacing arthroplasty implant (HR). a Histopathological evaluations of hematoxylin and eosin stained sections (consecutive sections of the sections analyzed by XRF) revealed presence of micron sized particles (blue arrow) in an area of necrotic macrophages and submicron-particles and particle aggregates in areas with clusters of particle-laden macrophages (yellow arrows) (TKA), micron sized particles in a large area of cell necrosis adjacent to an area of dystrophic calcification (orange arrow) (mTHA) and infiltration of particle-laden macrophages in an area with presence of non-interconnected bone trabeculae (HR). b RGB imaging of the spatially resolved metal specific XRF signals at a step size of 60 nm indicates abundance of CoCrMo containing particles. c XRF-spectra of micron sized particles (dashed lines, see b) clearly demonstrate that these particles consist of Co, Cr and Mo.
Size frequency evaluation of particles from three different implant types revealed distribution pattern towards more frequent occurrence of particles in the nano- and submicron-scale. a–c Particle size distribution in periprosthetic bone marrow samples proximate to total knee arthroplasty implants (TKA), modular total hip arthroplasty implants (mTHA) and hip resurfacing implants (HR). d Particle size distribution of all analyzed particles follows the lognormal model. e Separation of frequencies of particle sizes into different size ranges indicates the lowest proportion of microparticles in the HR group
Analysis of the elemental ratios of the CoCrMo particles located in the bone marrow revealed distinct differences of particle compositions with respect to particle sizes. a Particles released from total knee arthroplasty implants (TKA) and hip resurfacing implants (HR) indicate a distinct particle size-dependent decrease of Co to Cr ratios. Gray bar indicates the Co to Cr ratio in commonly used CoCrMo alloy (2.0–2.5). b Size-dependent Co to Mo ratio in particles released from all analyzed implant types. Gray bar indicates the Co to Mo ratio in commonly used CoCrMo alloy (8.6–14.7). c The Cr to Mo ratio is not influenced by particle size in particles released from TKA and HR implants while particles from mTHA implants are characterized by a size-dependent decrease of the Cr to Mo ratio. Gray bar indicates the Cr to Mo ratio in commonly used CoCrMo alloy (3.7–6.7). d Comparison of the XRF-spectra of submicron sized particles (left) and micron sized particles (right) released from a TKA implant clearly demonstrate that smaller particles are characterized by a lower Co content in relation to Cr and Mo
Particles released from cobalt-chromium-molybdenum (CoCrMo) alloys are considered common elicitors of chronic inflammatory adverse effects. There is a lack of data demonstrating particle numbers, size distribution and elemental composition of bone marrow resident particles which would allow for implementation of clinically relevant test strategies in bone marrow models at different degrees of exposure. The aim of this study was to investigate metal particle exposure in human periprosthetic bone marrow of three types of arthroplasty implants. Periprosthetic bone marrow sections from eight patients exposed to CoCrMo particles were analyzed via spatially resolved and synchrotron-based nanoscopic X-ray fluorescence imaging. These analyses revealed lognormal particle size distribution patterns predominantly towards the nanoscale. Analyses of particle numbers and normalization to bone marrow volume and bone marrow cell number indicated particle concentrations of up to 1 × 10¹¹ particles/ml bone marrow or 2 × 10⁴ particles/bone marrow cell, respectively. Analyses of elemental ratios of CoCrMo particles showed that particularly the particles’ Co content depends on particle size. The obtained data point towards Co release from arthroprosthetic particles in the course of dealloying and degradation processes of larger particles within periprosthetic bone marrow. This is the first study providing data based on metal particle analyses to be used for future in vitro and in vivo studies of possible toxic effects in human bone marrow following exposure to arthroprosthetic CoCrMo particles of different concentration, size, and elemental composition. Graphical abstract
In vivo porcine liver injury and intervention application
This shows the representative images of the porcine liver injury in vivo surgery: a the part of the liver is marked for avulsion; b the injured section of the liver is shown from which the liver tissue was avulsed; c the sprinkled Ta-MBG powder; d the bleeding site with Ta-MBG at 5 min time point; e sprinkled AristaTM powder; f the bleeding site with AristaTM at 5 min time point; g the bleeding site with Ta-MBG at 10 min time point; folding of the liver is evident here (arrows); h blood clot (arrows) at the injured site with Ta-MBG
This shows the representative site from where liver tissue was taken for histopathology
Blood clot evaluation. It shows SEM images of the blood clots: aclot without a sample: a physiological blood clot shows RBCs entrapped in the fibrin meshwork; bclot with AristaTM: the AristaTM particles are fused to form a flat sheet below which a blood clot (RBCs entangled in the fibrin meshwork) is seen, cclot with Ta-MBG: a blood clot is seen around Ta-MBG particles and glass particles are seen to agglomerate with the RBCs and fibrin meshwork; and dhigh-resolution image of blood clot with Ta-MBG: the arrows represent the area where fibrin network is seen to connect with the glass particles; the area marked by a dotted circle shows a glass particle from which multiple fibrin fibers seem to originate
Histopathological evaluation. Histology images of the liver tissue: a and b show the presence and absence of adherent clots at 10×; c and d show hemorrhage extent at 50×; e and f show the necrosis extent at 100×. a Liver tissue displays no adherent clot (−) before the intervention; no dark reddish stains representing adherent clots are seen. b Liver tissue shows extensive adherent clot (+++) following hemostatic interventions; abundant dark reddish stained tissue (arrows) means adherent clot. c Liver tissue does not show any bleeding at the start of the procedure; d Liver parenchyma shows 60% hemorrhage with an extent of 1.76 mm; redness in the interstitial parenchyma (arrows) is representative of the bleeding. e Liver tissue does not show any necrosis at the start of the procedure; f represents a maximum necrosis extent of the liver tissue seen in the study; light pink stained tissue (arrows) represents the necrotic areas while red-stained area shows hemorrhage associated with the necrosis
This study evaluates compositions of tantalum-containing mesoporous bioactive glass (Ta-MBG) powders using a porcine fatal liver injury model. The powders based on (80-x)SiO2-15CaO-5P2O5-xTa2O5 compositions with x = 0 (0Ta/Ta-free), 1 (1Ta), and 5 (5Ta) mol% were made using a sol–gel process. A class IV hemorrhage condition was simulated on the animals; hemodynamic data and biochemical analysis confirmed the life-threatening condition. Ta-MBGs were able to stop the bleeding within 10 min of their application while the bleeds in the absence of any intervention or in the presence of a commercial agent, AristaTM (Bard Davol Inc., Rhode Island, USA) continued for up to 45 min. Scanning electron microscopy (SEM) imaging of the blood clots showed that the presence of Ta-MBGs did not affect clot morphology. Rather, the connections seen between fibrin fibers of the blood clot and Ta-MBG powders point towards the powders’ surfaces embracing fibrin. Histopathological analysis of the liver tissue showed 5Ta as the only composition reducing parenchymal hemorrhage and necrosis extent of the tissue after their application. Additionally, 5Ta was also able to form an adherent clot in worst-case scenario bleeding where no adherent clot was seen before the powder was applied. In vivo results from the present study agree with in vitro results of the previous study that 5Ta was the best Ta-MBG composition for hemostatic purposes. Graphical abstract
Under whole body vibration, how the cement augmentation affects the vibration characteristic of the osteoporotic fusion lumbar spine, complications, and fusion outcomes is unclear. A L1-L5 lumbar spine finite element model was developed to simulate a transforaminal lumbar interbody fusion (TLIF) model with bilateral pedicle screws at L4-L5 level, a polymethylmethacrylate (PMMA) cement-augmented TLIF model (TLIF-PMMA) and an osteoporotic TLIF model. A 40 N sinusoidal vertical load at 5 Hz and a 400 N preload were utilized to simulate a vertical vibration of the human body and the physiological compression caused by muscle contraction and the weight of human body. The results showed that PMMA cement augmentation may produce a stiffer pedicle screw/rod construct and decrease the risk of adjacent segment disease, subsidence, and rod failure under whole-body vibration(WBV). Cement augmentation might restore the disc height and segmental lordosis and decrease the risk of poor outcomes, but it might also increase the risk of cage failure and prolong the period of lumbar fusion under WBV. The findings may provide new insights for performing lumbar interbody fusion in patients affected by osteoporosis of the lumbar spine. Graphical abstract
Multichannel structures in the design of nerve conduits offer potential advantages for regeneration of damaged nerves. However, lack of biochemical cues and electrical stimulation could hamper satisfactory nerve regeneration. The aim of this study was to simultaneously evaluate the effects of topographical, biological, and electrical cues on sciatic nerve regeneration. Accordingly, a series of multichannel nerve conduit was made using longitudinally-aligned laminin-coated poly (lactic-co-glycolic acid) (PLGA)/carbon nanotubes (CNT) nanofibers (NF, mean diameter: 455 ± 362 nm) in the lumen and randomly-oriented polycaprolactone (PCL) NF (mean diameter: 340 ± 200 nm) on the outer surface. In vitro studies revealed that the materials were nontoxic and able to promote cell attachment and proliferation on nanofibers and on fibrin gel. To determine the influence of laminin as biological and CNT as electrical cues on nerve regeneration, either of hollow PCL conduits, PLGA NF-embedded, PLGA/CNT NF-embedded or laminin-coated PLGA/CNT NF-embedded PCL conduits were implanted in rats. A new surgery method was utilized and results were compared with an autograft. The results of motor and sensory tests in addition to histopathological examination of the regenerated nerves demonstrated the formation of nerve fibers in laminin-coated PLGA/CNT NF-embedded PCL conduits. Results suggested that these conduits have the potential to improve sciatic nerve regeneration. Graphical abstract
Here, we introduce Ag substituted octacalcium phosphate (OCP-Ag) blocks with interconnected porous structure and sufficient mechanical strength as bone substitute (i.e., foam). We employed a two-step process for fabrication, which includes a setting reaction for acidic calcium phosphate granules using an acidic phosphate solution and a phase conversion process via dissolution-precipitation method in cocktail ((NH4)2HPO4-NH4NO3-NaNO3-AgNO3) solutions. The Ag contents in the fabricated OCP-Ag foams were 0.08–0.15 at%, which were sufficient in exhibiting contact antibacterial ability. The mechanical strength and porosity of the OCP-Ag foams were about 0.5 MPa and 70%, respectively. These values were sufficient for the application of the OCP-Ag foams as bone substitute. Graphical abstract
Biofilm accumulation on the polymethyl methacrylate (PMMA) restorations negatively affect the prognosis of the provisional restorations or the following treatment. This study developed a novel antibacterial PMMA resin containing low concentration of dimethylaminohexadecyl methacrylate (DMAHDM). Four resins were tested: (1) PMMA resin (Control), (2) 1.25% DMAHDM, (3) 2.5% DMAHDM, (4) 5% DMAHDM. Adding 1.25% DMAHDM into the PMMA resin did not influence the mechanical properties, degree of conversion, monomer releasing, and color stability of the specimens (p > 0.05). The incorporation of DMAHDM into PMMA resin could greatly prevent saliva-derived biofilms adhesion compared with the control group (p < 0.05). The metabolism level of saliva-derived biofilms on the 1.25%, 2.5%, and 5% DMAHDM resins were reduced by 20%, 54%, and 62%, respectively. And the mechanism of DMAHDM disturbing the integrity of bacterial cell walls was confirmed by flow cytometric analysis. Adding 1.25% and 2.5% DMAHDM did not compromise cytocompatibility of the modified resin (p > 0.05). Therefore, novel PMMA resin containing low concentration DMAHDM is promising as a future antimicrobial provisional restoration material for preventing microbial-induced complications in clinical settings. Graphical abstract
Hand tendon injuries represent a major clinical problem and might dramatically diminish a patient’s life quality. In this study, a targeted solution for flexor tendon repair was developed by combining a mechanical and biological approach. To this end, a novel acrylate-endcapped urethane-based polymer (AUP) was synthesized and its physico-chemical properties were characterized. Next, tubular repair constructs were developed using electrospinning of the AUP material with incorporated naproxen and hyaluronic acid (i.e. anti-inflammatory and anti-adhesion compounds, respectively), and with a tubular braid as mechanical reinforcement. Tensile testing of the repair constructs using ex vivo sheep tendons showed that the developed repair constructs fulfilled the required mechanical properties for tendon repair (i.e. minimal ultimate stress of 4 MPa), with an ultimate stress of 6.4 ± 0.6 MPa. Moreover, in vitro biological assays showed that the developed repair tubes and the incorporated bioactive components were non-cytotoxic. In addition, when equine tenocytes and mesenchymal stem cells were co-cultured with the repair tubes, an increased production of collagen and non-collagenous proteins was observed. In conclusion, this novel construct in which a mechanical approach (fulfilling the required mechanical properties) was combined with a biological approach (incorporation of bioactive compounds), shows potential as flexor tendon repair application. Graphical abstract
Ti-Zr alloys have gained increasing attention as a new metallic biomaterial, being used as implants for both orthopedics and dentistry. More recently, our group found promising results for the Ti-45Zr alloy, which presented a low elastic modulus, a pronounced and excellent mechanic character, and excellent cell compatibility in vitro. However, its biocompatibility and potential to promote osteogenesis in vivo remained unclear. In the present study, the biocompatibility, osteointegration ability, and immune response effects of the Ti-45Zr alloy were evaluated in animal experiments. The results showed that the alloy had good blood compatibility and no body side effects. After implantation in vivo, the inflammation turned out well and was beneficial to the polarization of macrophages. Additionally, the Ti-45Zr alloy presented a good osteointegration ability. Overall, these results confirmed that the Ti-45Zr alloy can be used as a dental implant material.
Methicillin resistance Staphylococcus aureus bacteria (MRSA) are serious hazards of bone implants. The present study was aimed to use the potential synergistic effects of Melittin and tetracycline to prevent MRSA associated bone implant infection. Chitosan/bioactive glass nanoparticles/tetracycline composite coatings were deposited on hydrothermally etched titanium substrate. Melittin was then coated on composite coatings by drop casting method. The surfaces were analyzed by FTIR, XRD, and SEM instruments. Tetracycline in coatings revealed multifunctional behaviors include bone regeneration and antibacterial activity. Releasing ALP enzyme from MC3T3 cells increased by tetracycline, so it is suitable candidate as osteoinductive and antibacterial agent in orthopedic implants coatings. Melittin increased the proliferation of MC3T3 cells. Composite coatings with combination of tetracycline and Melittin eradicate all MRSA bacteria, while coatings with one of them could no t eradicate all of the bacteria. In conclusion, chitosan/bioactive glass/tetracycline/Melittin coating can be suggested as a multifunctional bone implant coating because of its osteogenic and promising antibacterial activity. Graphical abstract
The surface of Tecoflex SG-80A Polyurethane (PU) films was modified by grafting polyethylene glycol (PEG) chains at three different molar amounts (0.05, 0.10, and 0.15 mmol). The resulting substrata were characterized by FTIR-ATR, TGA, AFM, SEM and contact angle to assess the surface modifications occurred during the grafting reactions. Osteoblasts and fibroblasts were cultured with PU extracts for 24 h, and their cell viability and morphology were evaluated by CellTiterBlue assay, Crystal Violet staining and Live/Dead assay. FTIR and TGA results indicated that PEG chains were successfully grafted onto PU surfaces, specifically in the hard segment of PU forming allophanate groups as the PEG grafting density increased. SEM and AFM images suggest that PU substrata were partially covered by PEG, increasing the dispersive and basic components of the PU surface energy. It was found that extracts from PEG-grafted polyurethanes increased the osteoblast viability, although fibroblasts viability remained constant regardless PEG grafting density; in spite of this both cells presented a more spread morphology at the lower PEG grafting density. Our results showed that surface energy of PU substrata can be tuned by PEG grafting density; also, the PEG leached tends to increase the pH of culture medium which leads to a higher viability of osteoblasts; nevertheless, PEG grafting density should be optimized to promote a healthy cell morphology as alterations in its morphology were detected at higher concentrations. Graphical abstract
This study investigated the corrosion susceptibility of pure titanium under uric acid exposure for 7 days based on surface analysis. The prepared pure titanium specimens, exposed to different concentrations of uric acid, were examined for surface microstructure, surface element composition and surface wettability using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and static contact angle measurement, respectively. The corrosion behaviors of titanium specimens were measured by open-circuit potential (OCP), electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization. The titanium ion release from the prepared specimens, which were immersed in Hank’s balanced salt solution (HBSS) containing different amount of uric acid, was measured by inductively coupled plasma atomic emission spectrometry (ICP-AES). More irregular pitting holes were observed on titanium surfaces exposed to a high concentration of uric acid, and XPS analyses revealed that the amount of titanium dioxide (TiO2) decreased. Titanium surfaces pre-treated with high uric acid became more hydrophobic. Furthermore, the results of OCP and potentiodynamic polarization tests showed increased corrosion susceptibility of titanium samples, while EIS data indicated more active corrosion behavior of titanium materials. The high concentration of uric acid also induced titanium ion release. High concentration of uric acid negatively influenced the surface characteristics and corrosion properties of titanium materials, which destroyed the titanium oxide film barrier. High uric acid exposure increased corrosion susceptibility of pure titanium specimens and accelerated titanium ion release. Graphical abstract
The medical application of chitosan (Cs) has been for about half a century, but the molecular mechanism has not been elucidated yet. This study is to explore the antibacterial mechanism of chitosan nanoparticles (Csnp) in dentin at the atomic resolution level. Extracted tooth specimen was prepared in three groups: A. control group; B. Csnp treatment under ultrasonic agitation (UA); C. Csnp treatment without UA. A scanning electron microscope (SEM) was used to observe the Csnp distribution on the dentin surface. The incubations of Enterococcus faecalis (E. faecalis) were performed. Further, we explored the protection mechanism of chitosan polymers to collagen type I, using molecular docking technique and crystal structure superimposition analysis. We revealed that Csnp under UA was evenly distributed on the dental surface and the Csnp-pretreated dentin had great antibacterial activity for E. faecalis. Our work demonstrated that Csnp occupied the grooves of the triple-helical collagen surface, strengthened by crosslinking, and interfered with the bond of collagen adhesin through steric hindrance effect and interrupting hydrophobic interaction. Csnp protects dentin against E. faecalis by interacting and crosslinking with collagen type I and prevents bacterial collagen adhesin binding through steric hindrance effect and interrupting hydrophobic interaction. Graphical abstract
This study aims to evaluate the feasibility and cardio-protective effects of biocompatible silicon-built restraint device (ASD) in the rat’s heart failure (HF) model. The performance and compliance characteristics of the ASD device were assessed in vitro by adopting a pneumatic drive and ball burst test. Sprague-Dawley (SD) rats were divided into four groups (n = 6); control, HF, HF + CSD, and HF + ASD groups, respectively. Heart failure was developed by left anterior descending (LAD) coronary artery ligation in all groups except the control group. The ASD and CSD devices were implanted in the heart of HF + ASD and HF + CSD groups, respectively. The ASD’s functional and expansion ability was found to be safe and suitable for attenuating ventricular remodeling. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. At the same time, hemodynamic parameters of the HF + ASD group improved systolic and diastolic functions, reducing ventricular wall stress, which indicated reverse remodeling. The BNP values were reduced in the HF + ASD group, which confirmed ASD feasibility and reversed remodeling at a molecular level. Furthermore, the HF + ASD group with no fibrosis suggests that ASD has significant curative effects on the heart muscles. In conclusion, ASD was found to be a promising restraint therapy than the previously standard restraint therapies. Stepwise ASD fabrication process (a) 3D computer model of ASD was generated by using Rhinoceros 5.0 software (b) 3D blue wax model of ASD (c) Silicon was prepared by mixing the solutions (as per manufacturer instruction) (d) Blue wax model of ASD was immersed into liquid Silicon (e) ASD model was put into the oven for 3 hours at 50 °C. (f) Blue wax started melting from the ASD model (g) ASD model was built from pure silicon (h) Two access lines were linked to the ASD device, which was connected with an implantable catheter (Port-a-cath), scale bar 100 µm. (Nikon Ldx 2.0).
Detergent treatment is the most commonly used method for the decellularization of ligaments and tendon grafts. However, it is well recognized that detergent treatment can also adversely affect the extracellular matrix. This study found that discission into the aponeurosis layer of the patellar tendon (PT) before decellularization is conducive to extracting cells from the PT using a low quantity of detergent in a short time period. The acellular aponeurosis discission ligament (AADL) retains its native collagen fibril structure and mechanical properties. Moreover, the PT retained cell and tissue compatibility in vitro and in vivo. After implantation into a defective allogeneic PT, we found that the AADL healed well in the host, and its collagen structure exhibited gradual improvement 12 months after implantation with satisfactory reconstruction. Impact The aponeurosis of tendons/ligaments is the main barrier to achieving complete decellularization, and it thus prevents complete recellularization for applications in tissue engineering. Aponeurosis can obstruct the removal of cell components. We found that excising the aponeurosis before decellularization allows for the removal of cellular components with a reduced amount of detergent, thus improving the biological properties of the acellular ligament. To the best of our knowledge, no similar studies have been performed. Graphical abstract
Until now, a few studies have been conducted on the destructive effects of TiO2 NPs in living organisms, and studies on the toxicity of TiO2 NPs are still in the beginning phases. Because of the widespread use of TiO2 NPs in all areas of human life, it is essential to study their profound and fundamental toxic effects on each organ and body cell. Herein, we evaluate the effect of exposure to TiO2 NPs on in vitro models derived from the rat bone marrow and adipose tissues. Exposure to TiO2 NPs at 100 and 200 μg/ml exhibited cytotoxicity for the rat bone marrow mesenchymal stem cells (rBMSCs) and rat adipose mesenchymal stem cells (rATSC), respectively. Additionally, reduced rBMSCs and rATSCs frequencies in the S phase of the cell cycle. Moreover, TiO2 NPs enhanced the activity of cellular senescence-associated β-galactosidase in both model cells. Significantly higher relative expression of aging-related genes P53 and NF-kB (p < 0.05) and lower expression levels of anti-aging-related genes Nanog and SIRT1 were found in the treated cells (p < 0.05). Colony-forming and DAPI staining showed the reduction of cell growth and DNA damage in both rBMSCs and rATSCs. Our findings along with other similar findings showed that TiO2 NPs probably have negative effects on the cell growth, prompt the cells for entry into proliferation stop, DNA damage, and trigger the aging process. Graphical abstract
The identified parameters for the bovine Achilles tendon
Inspired by Meyers et al. (Science, 2013), a piecewise model is established so as to individually predict both the heel region and the linear region of stress–strain curve. When the piecewise model satisfactorily predicts the experimental data, the constitutive parameters are precisely identified with definite physical significances. Along with this piecewise guideline, a complete constitutive model can be established for the whole stress–strain curve of collagen fiber tissues with the failure region as well. Graphical abstract
Bioengineered pancreatic β-islets have been widely advocated for the research and treatment of diabetes by offering both suitable cell culture models for the study of the pathology and the testing of new drugs and a therapy in those patients no longer responding to insulin administration and as an alternative to the shortage of donors for organ and islet transplantation. Unlike most of the studies published so far where pancreatic islets of pancreatic β-cells are encapsulated in hydrogels, this study demonstrate the formation of bioengineered pancreatic islets through cell anchoring to a gelatine-based biomaterial, PhenoDrive-Y, able to mimic the basement membrane of tissues. Through simple culture conditions, PhenoDrive-Y led human pancreatic β-cell lines and human umbilical endothelial cell lines to form organized structures closely resembling the natural vascularized pancreatic islets. When compared to gelatine, the cultures in presence of PhenoDrive-Y show higher degree of organization in tissue-like structures, a more pronounced endothelial sprouting and higher expression of typical cell markers. Noticeably, when challenged by hyperglycaemic conditions, the cells embedded in the PhenoDrive-Y assembled spheroids responded with higher levels of insulin production. In conclusion, the present work demonstrates the potential of PhenoDrive-Y as substrate for the development of bioengineered vascularized pancreatic islets and to be particularly suitable as a model for in vitro studies and testing of new therapeutics. Graphical abstract
Mean Vickers surface hardness of various concentrations of zeolite in Ag-reinforced GIC before and after 1 week of storage in water (n = 10). Note: Means with letters a/b did not have a statistically significant difference (p > 0.05) when compared to their respective controls. All means 24 h after fabrication did not have a statistically significant difference (p > 0.05) compared to means 1 week after water sorption. This is shown by letters c–g across the concentration groups
Mean water sorption and water solubility of various concentrations of zeolite in Ag-reinforced GIC (n = 12). Note: The letter a represents the absence of a statistically significant difference between the mean of the sample group as compared to the water sorption control (p > 0.05). The letter b indicates that there is no statistically significant difference between the mean of the sample groups as compared to the water solubility control (p > 0.05)
Mean flexural strength (Fs in MPa) of various concentrations of zeolite in Ag-reinforced GIC (n = 10). Note: Means with the letter a did not have a statistically significant difference when compared to the control
Zeolite can impart antibacterial properties to dental materials in the long-term when incorporated with inorganic cations. However, due to its porosity, it may jeopardize the mechanical integrity of the dental material. The aim of this project was to determine the effect on physical properties when zeolite is added to commercially available Ag-reinforced Glass Ionomer Cement (GIC). Sample groups were prepared according to the percentage of zeolite-clinoptilolite (0% - control, 0.5%, 1%, 2%, and 4% wt) added to Ag-GIC. Water sorption, solubility, Vickers hardness, and flexural strength were determined. Specifically, 10 × 2 mm circular disks were fabricated for the Vickers hardness, water sorption, and water solubility tests and 25 × 5 × 2 mm bars were created for the flexural strength test. The results from the surface hardness, water sorption, and flexural strength tests suggested that adding 0.5–4% wt of zeolite to Ag-reinforced GIC did not diminish its physical properties. However, the water solubility results showed that higher concentrations (2–4% wt) of zeolite had a statistically significant increase in water solubility compared to the control. Up to 4% wt zeolite can be incorporated into Ag-reinforced GIC without compromising mechanical properties. Incorporation of 0.5–1% wt zeolite to Ag-reinforced GIC will maintain an adequate surface hardness, water sorption, and flexural strength without compromising water solubility. Further research is needed to determine the effects of higher water solubility on clinical efficacy of zeolite modified Ag-GIC. Graphical abstract
The healing physiology of bone repair and remodeling that occurs after normal fracture is well orchestrated. However, it fails in complex clinical conditions and hence requires augmentation by grafts. In this study, composite nanohydroxyapatite (nHA), poly(hydroxybutyrate) (PHB) and poly(ɛ-caprolactone) (PCL) constituted microspheres sintered three-dimensional scaffold were evaluated in rabbit ulnar segmental defect. A composite scaffold using PHB-PCL-nHA microspheres was developed with protein interface by solvent/non-solvent sintering to provide multiple cues such as biocomposition, cancellous bone equivalent meso-micro multi-scale porosity, and compressive strength. In vitro DNA quantification and alkaline phosphatase (ALP) assays revealed that the protein interfaced composite scaffolds supported osteoblast proliferation and mineralization significantly higher than scaffolds without protein and TCPS (p < 0.05). Scanning electron micrographs of osteoblasts cultured scaffolds demonstrated cell-matrix interaction, cell spreading, colonization and filopodial extension across the porous voids. Cylindrical scaffolds (5 × 10 mm) were implanted following segmental defect (10 mm) in rabbit ulnar bone and compared with untreated control. Radiography (4, 8 and 12 weeks) and µ-computed tomography (12 weeks) analysis showed directional bone tissue formation by bridging defective site in both scaffolds with and without protein interface. Whereas, undesired sclerotic-like tissue formation was observed in control groups from 8 weeks. Histology by hot Stevenel’s blue and van Gieson’s picrofuchsin staining has confirmed enhanced bone maturation in scaffold groups while presence of osteoids was observed in control after 12 weeks. Thus, the developed composite matrices exhibits osteoinductive, osteoconductive properties and demonstrates its bone regenerative potential owing to its compositional, micro & macro structural and mechanical properties. Graphical abstract
Calcium phosphates are key biomaterials in dental treatment and bone regeneration. Biomaterials must exhibit antibacterial properties to prevent microbial infection in implantation frameworks. Previously, we developed various types of calcium phosphate powders (amorphous calcium phosphate, octacalcium phosphate (OCP), dicalcium phosphate anhydrate, and hydroxyapatite) with adsorbed protamine (which is a protein with antibacterial property) and confirmed their antibacterial property. In this study, as foundational research for the development of novel oral care materials, we synthesized calcium phosphate composite powders from three starting materials: i) OCP, which intercalates organic compounds, ii) protamine, which has antibacterial properties, and iii) F– ion, which promotes the formation of apatite crystals. Through investigating the preparation concentration of the F– ions and their loading into OCP, it was found that more F– ion could be loaded at higher concentrations regardless of the loading method. It was also observed that the higher the preparation concentration, the more the OCP converted to fluorapatite. The synthesized calcium phosphate composite powders were evaluated for biocompatibility through proliferation of MG-63 cells, with none of the powders exhibiting any growth inhibition. Antimicrobial tests showed that the calcium phosphate composite powders synthesized with protamine and F– ion by precipitation had enhanced antimicrobial properties than those synthesized by protamine adsorption. Thus, the calcium phosphate composite powder prepared from OCP, protamine, and F– ion forms the basis for promising antimicrobial biomaterials. Graphical abstract
Hydroxyapatite-carbon nanotubes (HA-CNTs) nanocomposite coating was applied by electrophoretic method on anodized Ti alloy to investigate its stability in simulated body fluid (SBF). The biocoating was characterized by using scanning electron microscope (SEM) for microstructure, X-ray diffraction (XRD) for crystallography. The effect of CNTs concentration on the coating properties was also investigated and found out that CNTs up to 5% has various improving effect on the system. It increased corrosion resistance and adhesion of the coating to the substrate and decreased the number of cracks on the coating. The results of the in vitro test showed that the cell viability increased with increasing the concentration of CNTs to 3 wt.% CNTs. Graphical abstract
Histology and immunohistochemistry of porcine coronary arteries implanted with PLLA-BVS follow-up to 90 d. The images were shown by HE staining (from left to right, first and second columns) and immunohistochemistry staining (third and fourth columns) of the coronary arteries after implantation for 0 d (a–d), 14 d (e–h), 28 d (i–l), 90 d (m–p), respectively. White squares in all pictures indicate components of PLLA stent, macrophages were indicated by black arrows at 28 and 90th day (j, n) in HE stain image, and positive immunohistochemistry staining of NF-κb/TNF-α were indicated by black arrows at 14 d, 28 d and 90 d (g, h, k, l, p).
Results of the positive staining of Oil Red O in foam cells treated with 25, 50, 100, 150 ug/ml Ox-LDL. Compared with blank control, the lipid drops in foam cells co-incubated with 25 ug/ml Ox-LDL were clear enough
ODs of macrophages in different concentration of GW9662. Note ODs of 20 μm GW9662 was highest in all the groups
Measurement results of inflammatory cytokines and PPARγ pathway signal by ELISA and RT-qPCR. a The release level of IL-6, TNF-α, IL-10 and LP-PLA2 detected by ELISA. The level of IL-6 and TNF-α in PLLA group significantly increased while comparing to the Con group, and decreased while comparing to the PLLA + Cur group. Compared with the PLLA + Con group, the levels of Lp-PLA2 were decreased in PLLA group. Compared with PLLA group, Lp-PLA2 increased in PLLA + Cur group. And compared with PLLA + Cur group, Lp-PLA2 increased in PLLA + Cur+GW9662 group. There were no significantly differences among each group of release levels of IL-10. b The mRNA level of IL-6, TNF-α, IL-10 and PPARγ detected by RT-qPCR. Compare to Con group, the levels of IL-6 and TNF-α mRNA significantly increased in PLLA group and decreased in PLLA + Cur group; the level of IL-10 and PPAR-γ mRNA significantly decreased in PLLA group and increased in PLLA + Cur group. In contrast, the level of PPAR-γ mRNA decreased in PLLA + Cur+GW9662 group while compare to PLLA + Cur group. (Compared with Con group, **p < 0.01, *p = < 0.05, respectively. Compared with PLLA group, ##p < 0.01, #p = < 0.05, respectively. Compared with PLLA + Cur group, &&p < 0.01, &p = < 0.05, respectively. Compared with Cur group, $$p < 0.01, $p = < 0.05, respectively)
Poly-L-lactic acid (PLLA) is considered to be a promising candidate material for biodegradable vascular scaffolds (BVS) in percutaneous coronary intervention (PCI). But, PLLA-BVS also faces the challenge of thrombosis (ST) and in-stent restenosis (ISR) caused by in-stent neo-atherosclerosis (ISNA) associated with inflammatory reactions in macrophage-derived foam cells. Our previous studies have confirmed that curcumin alleviates PLLA-induced injury and inflammation in vascular endothelial cells, but it remains unclear whether curcumin can alleviate the effect of inflammatory reactions in macrophage-derived foam cells while treated with degraded product of PLLA. In this study, PLLA-BVS was implanted in the porcine coronary artery to examine increased macrophages and inflammatory cytokines such as NF-κb and TNF-α by histology and immunohistochemistry. In vitro, macrophage-derived foam cells were induced by Ox-LDL and observed by Oil Red Staining. Foam cells were treated with pre-degraded PLLA powder, curcumin and PPARγ inhibitor GW9662, and the expression of IL-6, IL-10, TNF-α, NF-κb, PLA2 and PPARγ were investigated by ELISA or RT-qPCR. This study demonstrated that the macrophages and inflammatory factors increased after PLLA-BVS implantation in vivo, and foam cells derived from macrophages promoted inflammation by products of PLLA degradation in vitro. This present study was found that the inflammation of foam cells at the microenvironment of PLLA degraded products were significantly increased, and curcumin can attenuate the inflammation caused by the PLLA degradation via PPARγ signal pathway. In addition, curcumin should be further studied experimentally in vivo experiments on animal models as a potential therapeutic to reduce ISNA of PLLA-BVS. Graphical abstract
Water uptake behavior of different groups of artificial teeth with standard deviations error bars
Brands and respective groups of selected PMMA artificial teeth
Acrylic resins-based artificial teeth are frequently used for the fabrication of dentures has and contribute a very strong share in the global market. However, the scientific literature reporting the comparative analysis data of various artificial teeth is scarce. Focusing on that, the present study investigated various types of commercially available artificial teeth, composed of polymethyl methacrylate (PMMA). Artificial teeth are characterized for chemical analysis, morphological features, thermal analysis, and mechanical properties (surface hardness, compressive strength). Different types of artificial teeth showed distinct mechanical (compression strength, Vickers hardness) and thermal properties (thermal gravimetric analysis) which may be attributed to the difference in the content of PMMA and type and quantity of different fillers in their composition. Thermogravimetric analysis (TGA) results exhibited that vinyl end groups of PMMA degraded above 200°C, whereas 340-400°C maximum degradation temperature was measured by differential thermal analysis (DTA) for all samples. Crisma brand showed the highest compressive strength and young modulus (88.6 MPa and 1654 MPa) while the lowest value of Vickers hardness was demonstrated by Pigeon and Vital brands. Scanning electron microscope (SEM) photographs showed that Crisma, Pigeon, and Vital exhibited characteristics of a brittle fracture; however, Artis and Well bite brands contained elongated voids on their surfaces. According to the mechanical analysis and SEM data, Well bite teeth showed a significantly higher mechanical strength compared to other groups. However, no considerable difference was observed in Vickers hardness of all groups.
Vascular graft infections (VGI) are severe complications in prosthetic vascular surgery with an incidence ranging from 1 to 6%. In these cases, synthetic grafts are commonly used in combination with antimicrobial agents. Expanded polytetrafluoroethylene (ePTFE) is in clinical use as a synthetic graft material and shows promising results by influencing bacterial adhesion. However, the literature on antibiotic-bound ePTFE grafts is scarce. Gentamicin is a frequently used antibiotic for local treatment of surgical site infections, but has not been evaluated as antimicrobial agent on ePTFE grafts. In this study, we examine the antimicrobial efficacy and biocompatibility of novel types of gentamicin-coated ePTFE grafts in vitro. ePTFE grafts coated with gentamicin salt formulations with covalently-bound palmitate were evaluated in two drug concentrations (GP1.75% and GP3.5%). To investigate effects from types of formulations, also suspensions of gentamicin in palmitate as well as polylactide were used at comparable levels (GS + PA and GS + R203). Antibacterial efficacies were estimated by employing a zone of inhibition, growth inhibition and bacterial adhesion assay against Staphylococcus aureus (SA). Cytotoxicity was determined with murine fibroblasts according to the ISO standard 10993-5. Gentamicin-coated ePTFE grafts show low bacterial adherence and strong antibacterial properties in vitro against SA. Bactericidal inhibition lasted until day 11. Highest biocompatibility was achieved using gentamicin palmitate GP1.75% coated ePTFE grafts. ePTFE grafts with gentamicin-coating are effective in vitro against SA growth and adherence. Most promising results regarding antimicrobial properties and biocompatibility were shown with chemically bounded gentamicin palmitate GP1.75% coatings. Graphical abstract
Controlled pore size and desirable internal architecture of bone scaffolds play a significant role in bone regeneration efficiency. In addition to choosing appropriate materials, the manufacturing method is another significant factor in fabricating the ideal scaffold. In this study, scaffolds were designed and fabricated by the fused filament fabrication (FFF) technique. Polycaprolactone (PCL) and composites films with various percentages of hydroxyapatite (HA) (up to 20%wt) were used to fabricate filaments. The influence of (HA) addition on the mechanical properties of filaments and scaffolds was investigated. in vitro biological evaluation was examined as well as the apatite formation in simulated body fluid (SBF). The addition of HA particles increased the compressive strength and Young’s modulus of filaments and consequently the scaffolds. Compared to PCL, Young’s modulus of PCL/HA20% filament and three-dimensional (3D) printed scaffold has increased by 30% and 50%, respectively. Also, Young’s modulus for all scaffolds was in the range of 30–70 MPa, which is appropriate to use in spongy bone. Besides, the MTT assay was utilized to evaluate cell viability on the scaffolds. All the samples had qualified cytocompatibility, and it would be anticipated that addition of HA particles raise the biocompatibility in vivo. Alkaline phosphatase (ALP) evaluation shows that the addition of HA caused higher ALP activity in the PCL/HA scaffolds than PCL. Furthermore, calcium deposition in the PCL/HA specimens is higher than control. In conclusion, the addition of HA particles into the PCL matrix, as well as utilizing an inexpensive commercial FFF device, lead to the fabrication of scaffolds with proper mechanical and biological properties for bone tissue engineering applications. Graphical abstract
Amniotic membrane (AM) is a biological tissue that surrounds the fetus in the mother’s womb. It has pluripotent cells, immune modulators, collagen, cytokines with anti-fibrotic and anti-inflammatory effect, matrix proteins, and growth factors. In spite of the biological characteristics, some results have been released in preventing the adhesion on traumatized surfaces. Application of the AM as a scaffold is limited due to its low biomechanical resistance and rapid biodegradation. Therefore, for using the AM during surgery, its modification by different methods such as cross-linking of the membrane collagen is necessary, because the cross-linking is an effective way to reduce the rate of biodegradation of the biological materials. In addition, their cross-linking is likely an efficient way to increase the tensile properties of the material, so that they can be easily handled or sutured. In this regard, various methods related to cross-linking of the AM subsuming the composite materials, physical cross-linking, and chemical cross-linking with the glutraldehyde, carbodiimide, genipin, aluminum sulfate, etc. are reviewed along with its advantages and disadvantages in the current work.
Amniotic membrane (AM) is often applied as a substitute material during ocular surface reconstruction. However, since AM has several disadvantages, alternative materials must be considered for this application. Keratin films made from human hair (KFs) have previously been presented as a promising option; they exhibited suitable characteristics and satisfactory biocompatibility in an in vivo rabbit model. Nevertheless, dexamethasone (DEX) eye drops are necessary after surgery to suppress inflammation. Since eye drops must be administered frequently, this might result in poor patient compliance, and the release of DEX at the transplant site would be clinically beneficial. Therefore, we aimed to incorporate DEX into KFs without hindering the positive film characteristics. Drug-loaded KFs were generated either by suspension technique or by the addition of solubilizing agents. The resulting specimens were analyzed regarding appearance, loading capacity, transparency, mechanical characteristics, swelling behavior and in vitro release. Furthermore, biocompatibility was assessed in vitro by determining the cell viability, seeding efficiency and growth behavior of corneal epithelial cells. The amount of incorporated DEX influenced the transparency and biomechanical properties of the films, but even highly loaded films showed properties similar to those of AM. The suspension technique was identified as the best incorporation approach regarding chemical stability and prolonged DEX release. Moreover, suspended DEX in the films did not negatively impact cell seeding efficiencies, and the cell-growth behaviors on the specimens with moderate DEX loads were satisfactory. This suggest that these films could comprise a suitable alternative material with additional anti-inflammatory activity for ocular surface reconstruction. Graphical abstract
Top-cited authors
Aldo R. Boccaccini
  • Friedrich-Alexander-University of Erlangen-Nürnberg
Manzoor Koyakutty
  • Amrita Institute of Medical Sciences and Research Centre
Giuseppe Milano
  • Catholic University
Marta Barba
  • Catholic University of the Sacred Heart
Claudia Cicione
  • Università Campus Bio-Medico di Roma