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At the beginning of 2022, Frontiers in Bioengineering and Biotechnology - Biomaterials Section has published a Research Topic on “Functional Surfaces and Biomaterials.” The aim of this Research Topic is to summarize the current state of research and development in the field of functional surfaces and biomaterials with a particular focus on biotechnological and medical applications.
The guest editorial team would like to thank all colleagues from around the world who submitted their reviews and research articles for the Research Topic. By the end of August 2022, we have successfully collected 20 articles by 138 participating authors following the peer review process. We also tried to select manuscripts from different research areas to cover the most relevant Research Topic of interest, from drug delivery systems to bone tissue engineering to biosensors and general aspects in biomedicine. By the end of December, the 20 articles had been viewed for more than 21000 times with downloads more than 4,000 times, and 11 articles have reached more than 1,000 views.
Cytocompatibility analyses of new implant materials or biomaterials are not only prescribed by the Medical Device Regulation (MDR), as defined in the DIN ISO Norm 10993-5 and -12, but are also increasingly replacing animal testing. In this context, jellyfish collagen has already been established as an alternative to mammalian collagen in different cell culture conditions, but a lack of knowledge exists about its applicability for cytocompatibility analyses of biomaterials. Thus, the present study was conducted to compare well plates coated with collagen type 0 derived from Rhizostoma pulmo with plates coated with bovine and porcine collagen. The coated well plates were analysed in vitro for their cytocompatibility, according to EN ISO 10993-5/−12, using both L929 fibroblasts and MC3T3 pre-osteoblasts. Thereby, the coated well plates were compared, using established materials as positive controls and a cytotoxic material, RM-A, as a negative control. L929 cells exhibited a significantly higher viability (#### p < 0.0001), proliferation (## p < 0.01), and a lower cytotoxicity (## p < 0.01 and # p < 0.05)) in the Jellagen® group compared to the bovine and porcine collagen groups. MC3T3 cells showed similar viability and acceptable proliferation and cytotoxicity in all collagen groups. The results of the present study revealed that the coating of well plates with collagen Type 0 derived from R. pulmo leads to comparable results to the case of well plates coated with mammalian collagens. Therefore, it is fully suitable for the in vitro analyses of the cytocompatibility of biomaterials or medical devices.
The properties of polyelectrolyte multilayers are ruled by the process parameters employed during self-assembly. This is the first study in which a design of experiment approach was used to validate and control the production of ultrathin polyelectrolyte multilayer coatings by identifying the ranges of critical process parameters (polyelectrolyte concentration, ionic strength and pH) within which coatings with reproducible properties (thickness, refractive index and hydrophilicity) are created. Mathematical models describing the combined impact of key process parameters on coatings properties were developed demonstrating that only ionic strength and pH affect the coatings thickness, but not polyelectrolyte concentration. While the electrolyte concentration had a linear effect, the pH contribution was described by a quadratic polynomial. A significant contribution of this study is the development of a new approach to estimate the thickness of polyelectrolyte multilayer nanofilms by quantitative rhodamine B staining, which might be useful in all cases when ellipsometry is not feasible due to the shape complexity or small size of the coated substrate. The novel approach proposed here overcomes the limitations of known methods as it offers a low spatial sampling size and the ability to analyse a wide area without restrictions on the chemical composition and shape of the substrate.
High moisture permeability, excellent mechanical properties in a wet state, high water-holding capability, and high exudate absorption make bacterial nanocellulose (BNC) a favorable candidate for biomedical device production, especially wound dressings. The lack of antibacterial activity and healing-promoting ability are the main drawbacks that limit its wide application. Pullulan (Pul) is a nontoxic polymer that can promote wound healing. Zinc oxide nanoparticles (ZnO-NPs) are well-known as a safe antibacterial agent. In this study, aminoalkylsilane was chemically grafted on a BNC membrane (A-g-BNC) and used as a bridge to combine BNC with Pul-ZnO-NPs hybrid electrospun nanofibers. FTIR results confirmed the successful production of A-g-BNC/Pul-ZnO. The obtained dressing demonstrated blood clotting performance better than that of BNC. The dressing showed an ability to release ZnO, and its antibacterial activity was up to 5 log values higher than that of BNC. The cytotoxicity of the dressing toward L929 fibroblast cells clearly showed safety due to the proliferation of fibroblast cells. The animal test in a rat model indicated faster healing and re-epithelialization, small blood vessel formation, and collagen synthesis in the wounds covered by A-g-BNC/Pul-ZnO. The new functional dressing, fabricated with a cost-effective and easy method, not only showed excellent antibacterial activity but could also accelerate wound healing.
Controlled adhesion of HUVEC on polyelectrolyte multilayers by regulation of coating conditions
(2021)
Adhesion of host cells on the surface of implants is necessary for a healthy ingrowth of the implanted material. One possibility of surface modification is the coating of the implant with a second material with advantageous physical–chemical surface properties for the biological system. The coverage with blood proteins takes place immediately after implantation. It is followed by host–cell interaction on the surface. In this work, the effect of polyelectrolyte multilayer coatings (PEMs) on adhesion and activity of human umbilical vein endothelial cells (HUVECs) was studied. The PEMs were formed from poly(styrenesulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) from solutions with different concentrations of NaCl varying between 0 and 1.0 M. The adhesion of HUVEC and their viability on the PEM is related to the amount of adsorbed proteins from the applied cell growth medium. The amount of adsorbed proteins is controlled not only by the surface charge but also by the internal excess charge of the PEM. The internal excess charge of the PEM was controlled by changing the electrolyte concentration in the deposition solutions.
Background/Aim: The aim of this study was the conception, production, material analysis and cytocompatibility analysis of a new collagen foam for medical applications. Materials and Methods: After the innovative production of various collagen sponges from bovine sources, the foams were analyzed ex vivo in terms of their structure (including pore size) and in vitro in terms of cytocompatibility according to EN ISO 10993-5/-12. In vitro, the collagen foams were compared with the established soft and hard tissue materials cerabone and Jason membrane (both botiss biomaterials GmbH, Zossen, Germany). Results: Collagen foams with different compositions were successfully produced from bovine sources. Ex vivo, the foams showed a stable and long-lasting primary structure quality with a bubble area of 1,000 to 2,000 μm2. In vitro, all foams showed sufficient cytocompatibility. Conclusion: Collagen sponges represent a promising material for hard and soft tissue regeneration. Future studies could focus on integrating and investigating different additives in the foams.
Escherichia coli (E. coli) is considered the most common life-threatening infectious bacteria in our daily life and poses a major challenge to human health. However, antibiotics frequently overused and misused has triggered increased multidrug resistance, hinders therapeutic outcomes, and causes higher mortalities. Herein, we addressed near-infrared (NIR) laser-excited human serum albumin (HSA) mediated graphene oxide loaded palladium nano-dots (HSA-GO-Pd) that can effectively combat Gram-negative E. coli in vitro. NIR laser-excited designed hybrid material highly generates singlet oxygen and hydroxyl radical by electron spin-resonance (ESR) analysis. Transmission electron microscope (TEM) images show small spherical sizes PdNPs on the surface of GO nano-sheets. The zeta (ζ) potential study indicates that in an aqueous medium, the average PdNPs size and surface capped charge comes from human body protein (HSA), HSA-GO-Pd is 5–8 nm, and +25 mV, respectively. The spectroscopic characterization reveals that in the synthesized HSA-GO-Pd nanocomposite, PdNPs successfully well-dispersed decorated on the surface of graphene oxide. The as-synthesized HSA-GO-Pd shows excellent antibacterial activity against gram-negative pathogen by killing 95% bacteria within 5 h. HSA-GO-Pd having very biocompatible and shows significant antibacterial activities. Owing to their intense photothermal conversation potential, low toxicity to normal cells, the as-addressed hybrid (HSA-GO-Pd) combined with NIR-irradiation will catch up valuable insight into the effective ablation of pathogenic bacteria.
Despite its success against cancer, photothermal therapy (PTT) (>50 °C) suffers from several limitations such as triggering inflammation and facilitating immune escape and metastasis and also damage to the surrounding normal cells. Mild-temperature PTT has been proposed to override these shortcomings. We developed a nanosystem using HepG2 cancer cell membrane-cloaked zinc glutamate-modified Prussian blue nanoparticles with triphenylphosphine-conjugated lonidamine (HmPGTL NPs). This innovative approach achieved an efficient mild-temperature PTT effect by downregulating the production of intracellular ATP. This disrupts a section of heat shock proteins that cushion cancer cells against heat. The physicochemical properties, anti-tumor efficacy, and mechanisms of HmPGTL NPs both in vitro and in vivo were investigated. Moreover, the nanoparticles cloaked with the HepG2 cell membrane substantially prolonged the circulation time in vivo. Overall, the designed nanocomposites enhance the efficacy of mild-temperature PTT by disrupting the production of ATP in cancer cells. Thus, we anticipate that the mild-temperature PTT nanosystem will certainly present its enormous potential in various biomedical applications.
Polymeric micelle-like nanoparticles have demonstrated effectiveness for the delivery of some poorly soluble or hydrophobic anticancer drugs. In this study, a hydrophobic moiety, deoxycholic acid (DCA) was first bonded on a polysaccharide, chitosan (CS), for the preparation of amphiphilic chitosan (CS-DCA), which was further modified with a cationic glycidyltrimethylammounium chloride (GTMAC) to form a novel soluble chitosan derivative (HT-CS-DCA). The cationic amphiphilic HT-CS-DCA was easily self-assembled to micelle-like nanoparticles about 200 nm with narrow size distribution (PDI 0.08–0.18). The zeta potential of nanoparticles was in the range of 14 to 24 mV, indicating higher positive charges. Then, doxorubicin (DOX), an anticancer drug with poor solubility, was entrapped into HT-CS-DCA nanoparticles. The DOX release test was performed in PBS (pH 7.4) at 37 °C, and the results showed that there was no significant burst release in the first two hours, and the cumulative release increased steadily and slowly in the following hours. HT-CS-DCA nanoparticles loaded with DOX could easily enter into MCF-7 cells, as observed by a confocal microscope. As a result, DOX-loaded HT-CS-DCA nanoparticles demonstrated a significant inhibition activity on MCF-7 growth without obvious cellular toxicity in comparison with blank nanoparticles. Therefore, the anticancer efficacy of these cationic HT-CS-DCA nanoparticles showed great promise for the delivery of DOX in cancer therapy.
The physicochemical properties of synthetically produced bone substitute materials (BSM) have a major impact on biocompatibility. This affects bony tissue integration, osteoconduction, as well as the degradation pattern and the correlated inflammatory tissue responses including macrophages and multinucleated giant cells (MNGCs). Thus, influencing factors such as size, special surface morphologies, porosity, and interconnectivity have been the subject of extensive research. In the present publication, the influence of the granule size of three identically manufactured bone substitute granules based on the technology of hydroxyapatite (HA)-forming calcium phosphate cements were investigated, which includes the inflammatory response in the surrounding tissue and especially the induction of MNGCs (as a parameter of the material degradation). For the in vivo study, granules of three different size ranges (small = 0.355–0.5 mm; medium = 0.5–1 mm; big = 1–2 mm) were implanted in the subcutaneous connective tissue of 45 male BALB/c mice. At 10, 30, and 60 days post implantationem, the materials were explanted and histologically processed. The defect areas were initially examined histopathologically. Furthermore, pro- and anti-inflammatory macrophages were quantified histomorphometrically after their immunohistochemical detection. The number of MNGCs was quantified as well using a histomorphometrical approach. The results showed a granule size-dependent integration behavior. The surrounding granulation tissue has passivated in the groups of the two bigger granules at 60 days post implantationem including a fibrotic encapsulation, while a granulation tissue was still present in the group of the small granules indicating an ongoing cell-based degradation process. The histomorphometrical analysis showed that the number of proinflammatory macrophages was significantly increased in the small granules at 60 days post implantationem. Similarly, a significant increase of MNGCs was detected in this group at 30 and 60 days post implantationem. Based on these data, it can be concluded that the integration and/or degradation behavior of synthetic bone substitutes can be influenced by granule size.