Journal of biomedical materials research. Part B, Applied biomaterials最新文献

Nonabsorbable polymers used in biomedical applications are assumed to be permanently stable based on short-term testing, but some may be susceptible to oxidative degradation over several years of implantation. Traditional in vitro oxidative degradation screenings employ hydrogen peroxide (H₂O₂) solutions. However, the inherent instability of H₂O₂ can compromise the consistency of oxidative conditions, especially over extended periods and at elevated temperatures used for accelerated testing. In this study, an automated reactive accelerated aging (aRAA) system, which integrates an electrochemical detection method and a feedback loop, was utilized to ensure precise control of H₂O₂ concentrations during polymer oxidative degradation testing. The reproducibility of the aRAA system was evaluated by comparing four identical setups. Its efficacy as an oxidation challenge was demonstrated on (i) medical-grade vitamin E (VE) blended ultra-high molecular weight polyethylene (UHMWPE) and (ii) highly crosslinked (HXL) UHMWPE as model materials. The aRAA-aged VE-UHMWPE and HXL-UHMWPE samples were also compared against samples aged via an existing accelerated aging standard, ASTM F2003-02(2022). Samples were analyzed using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy to calculate their oxidation index per ASTM F2102-17. We observed that the aRAA system was more effective in oxidizing VE-UHMWPE and HXL-UHMWPE than the traditional ASTM F2003-02(2022) method. By providing a standardized and reliable approach to assess polymer oxidative degradation, the aRAA system could enhance the accuracy of long-term stability predictions for nonresorbable polymers in medical devices.

To develop standardized in vitro thrombogenicity test methods for evaluating medical device materials, three platelet activation biomarkers, beta-thromboglobulin (β-TG), platelet factor 4 (PF4), soluble p-selectin (CD62P), and a plasma coagulation marker, thrombin–antithrombin complex (TAT), were investigated. Whole blood, drawn from six healthy human volunteers into Anticoagulant Citrate Dextrose Solution A was recalcified and heparinized over a concentration range of 0.5–1.5 U/mL. The blood was incubated with test materials with different thrombogenic potentials for 60 min at 37°C, using a 6 cm²/mL material surface area to blood volume ratio. After incubation, the blood platelet count was measured before centrifuging the blood to prepare platelet-poor plasma (PPP) and platelet-free plasma (PFP) for enzyme-linked immunosorbent assay analysis of the biomarkers. The results show that all four markers effectively differentiated the materials with different thrombogenic potentials at heparin concentrations from 1.0 to 1.5 U/mL. When a donor-specific heparin concentration (determined by activated clotting time) was used, the markers were able to differentiate materials consistently for blood from all the donors. Additionally, using PFP instead of PPP further improved the test method's ability to differentiate the thrombogenic materials from the negative control for β-TG and TAT. Moreover, the platelet activation markers were able to detect reversible platelet activation induced by adenosine diphosphate (ADP). In summary, all three platelet activation markers (β-TG, PF4, and CD62P) can distinguish thrombogenic potentials of different materials and detect ADP-induced reversible platelet activation. Test consistency and sensitivity can be enhanced by using a donor-specific heparin concentration and PFP. The same test conditions are applicable to the measurement of coagulation marker TAT.

The development of new wound dressings made from biomaterials, which offer a better cost–benefit ratio and accelerate the healing process, is increasing nowadays. Various biopolymers can be electrospun to form functional membranes for wound healing. Therefore, in this study, chitosan and nanochitosan membranes with or without hyaluronic acid were prepared using the electrospinning technique, characterized and evaluated in the healing of skin wounds in rats. Chitosan and nanochitosan solutions, with or without hyaluronic acid, were prepared at concentrations of 1%–4% using PEO (polyethylene oxide) and subjected to the electrospinning process to obtain membranes characterized by scanning electron microscopy (SEM), mechanical tests, and antimicrobial activity. The healing effect of the membranes was evaluated by monitoring the area of the lesions, contraction of the wounds, histologic analysis, and induction of pro-inflammatory cytokine (IL-1 α and TNF-α) production in rats. The nanochitosan and nanochitosan membranes with hyaluronic acid achieved greater fiber diameter and uniformity, resistance, elasticity, and thermal stability, in addition to good adhesion to the wound bed and permeation capacity. Despite not presenting antimicrobial activity in vitro, they contributed to the production of pro-inflammatory interleukins in the animals tested, provided physical protection, reduced the wound area more markedly until the seventh day of the evaluation, with an acceleration of the healing process and especially when functionalized with hyaluronic acid. These results indicate that the membranes may be promising for accelerating the healing process of chronic wounds in humans.

The efficacy and osseointegration rate of an implant depend on its biocompatibility. Modern implantology seeks fast and reliable osseointegration, which is essential for clinical success. The objective of this research was to assess the osseointegration and biocompatibility of a titanium–titanium diboride composite (Ti-TiB₂) in rabbits in contrast to those of pure titanium (Ti). A total of 64 cylindrical implant specimens were fabricated, consisting of two sets: pure Ti (32 implants) and Ti-TiB₂ composite (32 implants). In this study, two implants were implanted per tibia (left and right tibias) in 16 white male New Zealand rabbits, for a total of four implants per rabbit (4 × 16 = 64 implants). A pushout test was used to assess implant specimen-bone bonding after 2 and 6 weeks of healing. The experiment utilized five rabbits per healing phase, which means that 20 implants per time point were used for the pushout tests. (10 for pure Ti and 10 for the composite). Histology was used to examine the tissue response to biocompatibility, and histomorphometry was used to measure new bone growth at the two time points. With three rabbits per time point, 12 implants were employed for the histological analyses. After implantation, the pushout shear strength results revealed that the mean shear strength of the Ti-TiB₂ implant specimens (5.4 ± 0.029 MPa for 2 weeks, 7.9 ± 0.029 MPa for 6 weeks) was statistically greater (p < 0.0001) than that of the pure Ti implant specimens (5.1 ± 0.015 MPa for 2 weeks, 6.6 ± 0.047 MPa for 6 weeks). After 2 weeks, woven bone tissues were observed around the pure titanium implants, and active osteoid tissue around the composite implants exhibited significant differences in new bone formation areas (NBFAs) (0.54 ± 0.004 mm² for Ti and 0.65 ± 0.003 mm² for the composite). After 6 weeks, there was new bone formation with osteocytes around the pure titanium implants (NBFA of 2.44 mm²) and osteoid maturation with the observation of reversal lines around the composite implants (NBFA of 2.89 mm²). The developed Ti-TiB₂ material was biocompatible and demonstrated superior bone growth compared to that of the pure Ti materials after 2 and 6 weeks.

Hydrogels have emerged as potential materials for bone grafting, thanks to their biocompatibility, biodegradation, and flexibility in filling irregular bone defects. In this study, we fabricated a novel NAH hydrogel system, composed of N,O-carboxymethyl chitosan (NOCC), aldehyde hyaluronic acid (AHA), and hydroxyapatite (HAp). To improve the mechanical strength of the fabricated hydrogel, a porous polycaprolactone (PCL) matrix was synthesized and used as a three-dimensional (3D) support template for NAH hydrogel loading, forming a novel PCL/NAH hybrid scaffold. A mixture of monosodium glutamate (M) and sucrose (S) at varied weight ratios (5M:5S, 7M:3S, and 9M:1S) was used for the fabrication of 3D PCL matrices. The morphology, interconnectivity, and water resistance of the porous PCL scaffolds were investigated for optimal hydrogel loading efficiency. The results demonstrated that PCL scaffolds with porogen ratios of 7M:3S and 9M:1S possessed better interconnectivity than 5M:5S ratio. The compressive strength of the PCL/NAH hybrid scaffolds with 9M:1S (561.6 ± 6.1 kPa) and 7M:3S (623.8 ± 6.8 kPa) ratios are similar to cancellous bone and all hybrid scaffolds were biocompatible. Rabbit models with tibial defects were implanted with the PCL/NAH scaffolds to assess the wound healing capability. The results suggest that the PCL/NAH hybrid scaffolds, specifically those with porogen ratio of 7M:3S, exhibit promising bone healing effects.

The stromal vascular fraction (SVF) is a derivate of fat tissue comprising both adipose-derived mesenchymal stem cells and endothelial cells and serves as a promising cell source for engineering vascularized bone tissues. Its combination with osteoconductive biphasic calcium phosphate (BCP) ceramic may represent a point-of-care agent for bone reconstruction. Here we assessed the proliferation and osteogenic differentiation capacities of SVF on 3D printed BCP implants, in comparison with isolated adipose-derived mesenchymal stem cells (AD-MSCs). AD-MSCs and SVF isolated from human donors were seeded on plastic or 3D printed BCP ceramics with sinusoidal or gyroid macrotopography and cultured in the presence or absence of osteogenic factors. Vascular, hematopoietic and MSC surface markers were assessed by flow cytometry whereas osteogenic activity was investigated through alizarin red staining and alkaline phosphatase activity. Osteogenic factors were necessary to trigger osteogenic activity when cells were cultured on plastic, without significant difference observed between the two cell populations. Interestingly, osteogenic activity was observed on BCP implants in the absence of differentiation factors, without significant difference in level activity between the two cell populations and macrotopography. This study offers supportive data for the use of combined BCP scaffolds with SVF in a perspective of a one-step surgical procedure for bone regeneration.