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Ferroptosis is a lipid peroxidation-driven cell death route and has attracted enormous interest for cancer therapy. Distinct from other forms of regulated cell death, its process is involved with multiple metabolic pathways including lipids, bioenergetics, iron, and so on, which influence cancer cell ferroptosis sensitivity and communication with the immune cells in the tumor microenvironment. Development of novel technologies for harnessing the ferroptosis-associated metabolic regulatory network would profoundly improve our understanding of the immune responses and enhance the efficacy of ferroptosis-dependent immunotherapy. Interestingly, the recent advances in bio-derived material-based therapeutic platforms offer novel opportunities to therapeutically modulate tumor metabolism through the in situ delivery of molecular or material cues, which not only allows the tumor-specific elicitation of ferroptosis but also holds promise to maximize their immunostimulatory impact. In this review, we will first dissect the crosstalk between tumor metabolism and ferroptosis and its impact on the immune regulation in the tumor microenvironment, followed by the comprehensive analysis on the recent progress in biomaterial-based metabolic regulatory strategies for evoking ferroptosis-mediated antitumor immunity. A perspective section is also provided to discuss the challenges in metabolism-regulating biomaterials for ferroptosis-immunotherapy. We envision that this review may provide new insights for improving tumor immunotherapeutic efficacy in the clinic., (© 2024 Wiley Periodicals LLC.)

The objective of the present study was to evaluate the carbon fiber obtained from textile PAN fiber, in its different forms, as a potential scaffolds synthetic bone. Thirty-four adult rats were used (Rattus norvegicus, albinus variation), two critical sized bone defects were made that were 5 mm in diameter. Twenty-four animals were randomly divided into four groups: control (C)-bone defect + blood clot, non-activated carbon fiber felt (NACFF)-bone defect + NACFF, activated carbon fiber felt (ACFF)-bone defect + ACFF, and silver activated carbon fiber felt (Ag-ACFF)-bone defect + Ag-ACFF, and was observed by 15 and 60 days for histomorphometric, three-dimensional computerized microtomography (microCT) and mineral apposition analysis. On histomorphometric and microCT analyses, NACFF were associated with higher proportion of neoformed bone and maintenance of bone structure. On fluorochrome bone label, there was no differences between the groups. NACFF has shown to be a promising synthetic material as a scaffold for bone regeneration., (© 2024 Wiley Periodicals LLC.)

Recent advances in both cardiac tissue engineering and hearts-on-a-chip are grounded in new biomaterial development as well as the employment of innovative fabrication techniques that enable precise control of the mechanical, electrical, and structural properties of the cardiac tissues being modelled. The elongated structure of cardiomyocytes requires tuning of substrate properties and application of biophysical stimuli to drive its mature phenotype. Landmark advances have already been achieved with induced pluripotent stem cell-derived cardiac patches that advanced to human testing. Heart-on-a-chip platforms are now commonly used by a number of pharmaceutical and biotechnology companies. Here, we provide an overview of cardiac physiology in order to better define the requirements for functional tissue recapitulation. We then discuss the biomaterials most commonly used in both cardiac tissue engineering and heart-on-a-chip, followed by the discussion of recent representative studies in both fields. We outline significant challenges common to both fields, specifically: scalable tissue fabrication and platform standardization, improving cellular fidelity through effective tissue vascularization, achieving adult tissue maturation, and ultimately developing cryopreservation protocols so that the tissues are available off the shelf., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

N/C-terminal protected amyloidogenic peptides are valuable biomaterials. Optimization of the protective structures at both termini is, however, synthetically laborious because a linear sequence of solid-phase peptide synthesis protocol (on-resin peptide assembly/peptide removal from resin/high-performance liquid chromatography purification) is required for the peptides each time the protective group is modified. In this study, we demonstrate a modular synthetic strategy for the purpose of rapidly deriving the N/C-terminal structures of amyloidogenic peptides. The precursor sequences that can be easily synthesized due to a non-amyloidogenic property were stocked as the synthetic intermediates. Condensation of the intermediates with N/C-terminal units in a liquid phase followed by high-performance liquid chromatography purification gave the desired peptides P1-P8. The amyloidogenic peptides that have various N/C-terminal protective structures were therefore synthesized in a labor-effective manner. This method is suggested to be useful for synthesizing amyloidogenic peptides possessing divergent protective structures at the N/C-terminus., (© 2023 European Peptide Society and John Wiley & Sons, Ltd.)

Eliminating endotoxins is a common problem in the development of biotechnologically produced pharmaceuticals or biomaterials. Residual endotoxins in the final sample may hamper the properties of the product or induce severe adverse effects. Developing an effective downstream purification protocol that ensures a lack of minimal endotoxin content in the final product can be a challenging task. In our previous studies, we developed nanospheres produced from bioengineered silks. Despite their good overall biocompatibility, in vivo characterization of spheres showed mild activation of the immune system (mainly in terms of anti-silk antibody production). Herein, we examined, if the endotoxins delivered with the silk spheres might have contributed to activating the adaptive immune response. We investigated various commercially available methods for endotoxin removal that can be applied as an extra step in downstream endotoxin removal from MS1-type silk proteins. We selected a method that allowed for a 10-fold reduction of endotoxin content in soluble silk and 2-fold in the final product (silk spheres). The reduced level of endotoxins improved the biocompatibility of the silk spheres as these particles induced negligible titers of anti-silk antibodies in an in vivo immune study. Since endotoxins can enhance life-threatening immune responses, it is crucial to optimize the method of their removal before clinical use not only of silk-based products but also of other biomolecules produced biotechnologically., (© 2023 Wiley Periodicals LLC.)

Focal chondral defects (FCDs) significantly impede quality of life for patients and impose severe economic costs on society. One of the most promising treatment options-autologous matrix-induced chondrogenesis (AMIC)-could benefit from a scaffold that contains both of the primary cartilage matrix components-sulfated glycosaminoglycans (sGAGs) and collagen type II. Here, 17 different protocols were evaluated to determine the most optimum strategy for decellularizing (decelling) the bovine nucleus pulposus (bNP) to yield a natural biomaterial with a cartilaginous constituency. The resulting scaffold was then characterized with respect to its biochemistry, biomechanics and cytocompatibility. Results indicated that the optimal decell protocol involved pre-crosslinking the tissue prior to undergoing decell with trypsin and Triton X-100. The residual DNA content of the scaffold was found to be 32.64 ± 9.26 ng/mg dry wt. of tissue with sGAG and hydroxyproline (HYP) contents of 72.53 ± 16.43. and 78.38 ± 8.46 μg/mg dry wt. respectively. The dynamic viscoelastic properties were found to be preserved (complex modulus: 17.92-16.62 kPa across a range of frequencies) while the equilibrium properties were found to have significantly decreased (aggregate modulus: 11.51 ± 9.19 kPa) compared to the non-decelled fresh bNP tissue. Furthermore, the construct was also found to be cytocompatible with bone marrow stem cells (BMSCs). While it was not permissive of cellular infiltration, the BMSCs were still found to have lined the laser drilled channels in the scaffold. Taken together, the biomaterial developed herein could be a valuable addition to the AMIC family of scaffolds or serve as an off-the-shelf standalone option for cartilage repair., (© 2023 Wiley Periodicals LLC.)

Meniscus-related injuries are a common orthopedic challenge with an increasing incidence in the population. While the preservation of viable meniscal tissue is the preferred approach in repair strategies, complex or total traumatic lesions may require alternative therapeutic approaches such as meniscal reconstruction using allografts or engineered equivalents. Although clinical studies suggest promising outcomes with the use of acellular implants, further development is needed to improve their biological and mechanical requirements. Decellularized extracellular matrix (dECM) derived from menisci is a promising biomaterial for meniscus tissue engineering due to its recapitulation of the native tissue environment and the maintenance of tissue-specific cues. However, the associated mechanical limitations of dECM-derived scaffolds frequently impedes their adoption, requiring additional reinforcement or combining with stiffer biomaterials to increase their load-bearing properties. In this study, decellularized extracellular matrix was extracted and its fibrillation was controlled by adjusting both pH and salt concentrations to fabricate mechanically functional meniscal tissue equivalents. The effect of collagen fibrillation on the mechanical properties of the dECM constructs was assessed, and porcine-derived fibrochondrocytes were used to evaluate in vitro biocompatibility. It was also possible to fabricate meniscus-shaped implants by casting of the dECM and to render the implants suitable for off-the-shelf use by adopting a freeze-drying preservation method. Suture pull-out tests were also performed to assess the feasibility of using existing surgical methods to fix such implants within a damaged meniscus. This study highlights the potential of utilizing ECM-derived materials for meniscal tissue substitutes that closely mimic the mechanical and biological properties of native tissue., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Millions of people have been reported with tendon injuries each year. Unfortunately, Tendon injuries are increasing rapidly due to heavy exercise and a highly aging population. In addition, the introduction of 3D-printing technology in the area of tendon repair and replacement has resolved numerous issues and significantly improved the quality of artificial tendons. This advancement has also enabled us to explore and identify the most effective combinations of biomaterials that can be utilized in this field. This review discusses the recent development of the 3D-printed artificial tendon; where recently, some research investigated the most suitable pore sizes, diameter, and strength for scaffolds to have high tendon cells ingrowth and proliferation, giving a better understanding of the effects of densities and structure patterns on tendon's mechanical properties. In addition, it presents the divergence between 3D-printed tendons and other tissue and how the different 3D-printing techniques and models participated in this development., (© 2024 Wiley Periodicals LLC.)

Bone defects treatment may require the use of biomaterials that behave as a support and promote bone regeneration. Limitations associated with the use of autografts and allografts make it necessary to design new synthetic bone substitutes. Some of the most promising biomaterials currently under investigation are based on nanocarbonate hydroxyapatite (nCHA). In this study, we studied the bone-inducing capacity of nCHA-based scaffolds alone (SAG) and enriched with osteostatin (SAGO) or with bone marrow aspirate(SAGB) after implantation for 12 weeks in a 15-mm long critical defect performed in the radius of New Zealand rabbits. Bone formation obtained was compared with a group with the unfilled defect (CE), as control group, and other with the defect filed with iliac crest autograft (GS), as gold standard. X-ray follow-up was performed at 2, 4, 6 and 12 weeks and μCT and histological studies at 12 weeks. The radiological results showed a greater increment in bone formation in the GS group (75%-100%), followed by the SAG and SAGB groups (50%-75%). μCT results showed an increase of bone volume/tissue volume values in GS group followed by SAG and SAGB groups (0.53, 0.40, and 0.31 respectively) compared with CE group (0.26). Histological results showed limited resorption of the nCHA scaffolds and partial osseointegration in the SAG and SAGB groups. However, in the SAGO group, the presence of connective tissue encapsulating the scaffold was detected. In SAG, SAGB, and increase of bone formation were observed compared with CE group, but less than the GS group. Thus, the investigated materials represent a significant advance in the design of synthetic materials for bone grafting, but further studies are needed to bring their in vivo behavior closer to autograft, the gold standard., (© 2024 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

In pursuit of a suitable scaffold material for cardiac valve tissue engineering applications, an acellular, electrospun, biodegradable polyester carbonate urethane urea (PECUU) scaffold was evaluated as a pulmonary valve leaflet replacement in vivo. In sheep (n = 8), a single pulmonary valve leaflet was replaced with a PECUU leaflet and followed for 1, 6, and 12 weeks. Implanted leaflet function was assessed in vivo by echocardiography. Explanted samples were studied for gross pathology, microscopic changes in the extracellular matrix, host cellular re-population, and immune responses, and for biomechanical properties. PECUU leaflets showed normal leaflet motion at implant, but decreased leaflet motion and dimensions at 6 weeks. The leaflets accumulated α-SMA and CD45 positive cells, with surfaces covered with endothelial cells (CD31+). New collagen formation occurred (Picrosirius Red). Accumulated tissue thickness correlated with the decrease in leaflet motion. The PECUU scaffolds had histologic evidence of scaffold degradation and an accumulation of pro-inflammatory/M1 and anti-inflammatory/M2 macrophages over time in vivo. The extent of inflammatory cell accumulation correlated with tissue formation and polymer degradation but was also associated with leaflet thickening and decreased leaflet motion. Future studies should explore pre-implant seeding of polymer scaffolds, more advanced polymer fabrication methods able to more closely approximate native tissue structure and function, and other techniques to control and balance the degradation of biomaterials and new tissue formation by modulation of the host immune response., (© 2023 Wiley Periodicals LLC.)

Porous NiTi (pNiTi) is a promising biomaterial for functional long-term implantation that has been produced using various manufacturing techniques and tested for biocompatibility. pNiTi produced using a more recent technology of Metal Injection Molding (MIM) has shown better physical and mechanical properties than those produced by earlier manufacturing methods, but its biocompatibility has yet to be determined. Hence, extracts from pNiTi dental implants produced by MIM were tested for cytotoxicity and genotoxicity in this work. Its toxicity was evaluated at the cellular and in vitro levels using elution and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Short-term testing revealed that pNiTi extract was cytocompatible with L-929 fibroblast and V79-4 lung cells, with no cell lysis or reactivity observed, respectively (USP grade 0). Following exposure to varied extract concentrations, good cell viability was observed where the lowest concentration showed the highest optical density (OD) and cell viability (2.968 ± 0.117 and 94%, respectively), and the highest concentration had the least OD and cell viability (2.251 ± 0.054 and 71%, respectively). pNiTi extracts demonstrated genocompatibility in two independent assays: mutagenic potential using a bacterial reverse mutation test and a clastogenic effect on chromosomes using the micronucleus test. Similar to the negative control reactions, there was no significant increase in revertant colonies following exposure to 100% pNiTi extract with and without metabolic activation (p = .00). No DNA clastogenic activity was caused by pNiTi at varied extract concentrations as compared to the negative control when tested with and without metabolic activation (p = .00). As a result, both cytotoxic and genotoxic investigations have confirmed that pNiTi dental implants utilizing the MIM process are cytocompatible and genocompatible in the short term, according to the International Standard, ISO 10993 - Parts 3, 5, and 33., (© 2023 Wiley Periodicals LLC.)

We engineered an in vitro model of bioartificial 3D bone organoid consistent with an anatomical and vascular microenvironment common to mammalian flat and short bones. To achieve this, we chose the decellularized-decalcified matrix of the adult male rat scapula, implemented with the reconstruction of its intrinsic vessels, obtained through an original intravascular perfusion with polylevolactic (PLLA), followed by coating of the PLLA-fabricated vascularization with rat tail collagen. As a result, the 3D bone and vascular geometry of the native bone cortical and cancellous compartments was reproduced, and the rat tail collagen-PLLA biomaterial could in vitro act as a surrogate of the perivascular extracellular matrix (ECM) around the wall of the biomaterial-reconstituted cancellous vessels. As a proof-of-concept of cell compatibility and site-dependent osteoinductive properties of this bioartificial 3D construct, we show that it in vitro leads to a time-dependent microtopographic positioning of rat mesenchymal stromal cells (MSCs), initiating an osteogenic fate in relation to the bone compartment. In addition, coating of PLLA-reconstructed vessels with rat tail collagen favored perivascular attachment and survival of MSC-like cells (mouse embryonic fibroblasts), confirming its potentiality as a perivascular stroma for triggering competence of seeded MSCs. Finally, in vivo radiographic topography of bone lesions in the human jaw and foot tarsus of subjects with primary osteoporosis revealed selective bone cortical versus cancellous involvement, suggesting usefulness of a human 3D bone organoid engineered with the same principles of our rat organoid, to in vitro investigate compartment-dependent activities of human MSC in flat and short bones under experimental osteoporotic challenge. We conclude that our 3D bioartificial construct offers a reliable replica of flat and short bones microanatomy, and promises to help in building a compartment-dependent mechanistic perspective of bone remodeling, including the microtopographic dysregulation of osteoporosis., (© 2023 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

Guided bone regeneration (GBR) is a treatment strategy used to recover bone volume. Barrier membranes are a key component of GBR protocols, and their properties can impact treatment outcomes. This study investigated the efficacy of an experimental, slow-degrading, bilayer barrier membrane for application in GBR using in vivo animal models. A synthetic copolymer of poly(lactic acid/caprolactone) (PLCL) was used to prepare a slow-degrading bilayer membrane. The biodegradability of PLCL was evaluated by subcutaneous implantation in a rat model. The barrier function of the PLCL membrane was investigated in a rat calvaria defect model and compared with commercially available membranes composed of type I collagen (Col) and poly(lactic-co-glycolic acid) (PLGA). An alveolar bone defect model in beagle dogs was used to simulate GBR protocols to evaluate the bone regeneration ability of the experimental PLCL membrane. The PLCL membrane showed slow biodegradation, resulting in an efficient and prolonged barrier function compared with commercial materials. In turn, this barrier function enabled the space-making ability of PLCL membrane and facilitated bone regeneration. In the alveolar bone defect model, significantly greater regeneration was achieved by treatment with PLCL membrane compared with Col and PLGA membranes. Additionally, a continuous alveolar ridge contour was observed in PLCL-treated bone defects. In conclusion, the PLCL bilayer membrane is a promising biomaterial for use in GBR given its slow degradation and prolonged barrier function., (© 2023 Wiley Periodicals LLC.)

Protein isolation is an essential tool in cell biology to characterize protein abundance under various experimental conditions. Several protocols exist, tailored to cell culture or tissue sections, and have been adapted to particular downstream analyses (e.g., western blotting or mass spectrometry). An increasing trend in bioengineering and cell biology is to use three-dimensional (3D) hydrogel-based scaffolds for cell culture. In principle, the same protocols can be used to extract protein from hydrogel-based cell and tissue constructs. However, in practice the yield and quality of the recovered protein pellet is often substantially lower when using standard protocols and requires tuning of multiple steps, including the selected lysis buffer and the scaffold homogenization strategy, as well as the methods for protein purification and reconstitution. We present here specific protocols tailored to common 3D hydrogels to help researchers using hydrogel-based 3D cell culture improve the quantity and quality of their extracted protein. We focus on three materials: protease-degradable PEG-based hydrogels, collagen hydrogels, and alginate hydrogels. We discuss how the protein extraction procedure can be adapted to the scaffold of interest (degradable or non-degradable gels), proteins of interests (soluble, matrix-bound, or phosphoproteins), and downstream biochemical assays (western blotting or mass spectrometry). With the growing interest in 3D cell culture, the protocols presented should be useful to many researchers in cell biology, protein science, biomaterials, and bioengineering communities. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolating proteins from PEG-based hydrogels Basic Protocol 2: Isolating proteins from collagen hydrogels Basic Protocol 3: Isolating proteins from alginate hydrogels Alternate Protocol: Isolating protein from alginate gels using EDTA to dissolve the gel Support Protocol: Isolating protein and RNA simultaneously from the same samples., (© 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Centrifugal spinning is a technology used to generate small diameter fibers and has been extensively studied for its vast applications in biomedical engineering. Centrifugal spinning is known for its rapid production rate and has inspired the creation of other technologies which leverage the high-speed rotation, namely Pressurized Gyration. Pressurized gyration incorporates a unique applied gas pressure which serves to provide additional control over the fiber production process. The resulting fibers are uniquely suitable for a range of healthcare-related applications that are thoroughly discussed in this work, which involve scaffolds for tissue engineering, solid dispersions for drug delivery, antimicrobial meshes for filtration and bandage-like fibrous coverings for wound healing. In this review, the notable recent developments in centrifugal spinning and pressurized gyration are presented and how these technologies are being used to further the range of uses of biomaterials engineering, for example the development of core-sheath fabrication techniques for multi-layered fibers and the combination with electrospinning to produce advanced fiber mats. The enormous potential of these technologies and their future advancements highlights how important they are in the biomedical discipline. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures., (© 2023 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

In the last decades, near-infrared (NIR) light has attracted considerable attention due to its unique properties and numerous potential applications in bioimaging and disease treatment. Bone tissue engineering for bone regeneration with the help of biomaterials is currently an effective means of treating bone defects. As a controlled light source with deeper tissue penetration, NIR light can provide real-time feedback of key information on bone regeneration in vivo utilizing fluorescence imaging and be used for bone disease treatment. This review provides a comprehensive overview of NIR light-facilitated bone tissue engineering, from the introduction of NIR probes as well as NIR light-responsive materials, and the visualization of bone regeneration to the treatment of bone-related diseases. Furthermore, the existing challenges and future development directions of NIR light-based bone tissue engineering are also discussed. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement., (© 2023 Wiley Periodicals LLC.)

Titanium and its alloys are used to make dental implants because of its low density, high strength, and corrosion resistance. This paper describes the development of a potential biomaterial Ti-10Nb by powder metallurgy utilizing four different compaction pressures and analyses its microstructural, physical, mechanical, electrochemical, biological, and tribological behavior under various situations. The alloys were fabricated using four different compaction pressures, that is, 600, 650, 700, and 750 MPa, and sintered in a vacuum atmosphere at 1000°C for 1.5 h. The density of the samples was measured using Archimedes principle. X-ray diffraction and scanning electron microscopy equipped with energy dispersive spectroscopy were used to investigate the phase composition and microstructure, and a profilometer was used to examine the surface roughness of various samples. Vickers hardness tester was used to evaluate hardness, and a universal testing machine was used for compression testing. Corrosion and wear behavior were examined using a potentiostat and a Bio-Tribometer, respectively. This Ti-10Nb alloys consist of α + β phase, and have 16% highest porosity in sample compacted at 600 MPa. The samples compacted at 750 MPa achieved highest hardness, yield strength, compressive strength, and elastic modulus of 450 ± 29.72 HV, 718.22 ± 16.37 MPa, 1543.59 ± 24.37 MPa, and 41.27 ± 3.29 GPa, respectively. In addition, it also possesses highest corrosion and wear resistance with lowest i corr of 0.3954 ± 0.008 μA/cm 2 and wear volume of (31.25 ± 0.206) × 10 -3  mm 3 . These results indicate that the developed alloys have a variety of desirable properties, including high hardness, adequate compressive strength, good corrosion and wear resistance, apatite-forming capability, and a low elastic modulus, which is advantageous for avoiding stress shielding. Therefore, it may be recommended to use it as a dental implant material., (© 2023 Wiley Periodicals LLC.)

Biomaterials for nucleus pulposus (NP) replacement and regeneration have great potential to restore normal biomechanics in degenerated intervertebral discs following nucleotomy. Mechanical characterizations are essential for assessing the efficacy of biomaterial implants for clinical applications. While traditional compression tests are crucial to quantify various modulus values, relaxation behaviors and fatigue resistance, rheological measurements should also be conducted to investigate the viscoelastic properties, injectability, and overall stability upon deformation. To recapitulate the physiological in vivo environment, the use of spinal models is necessary to evaluate the risk of implant extrusion and the restoration of biomechanics under different loading conditions. When designing devices for NP replacement, injectable materials are ideal to fully fill the nucleus cavity and prevent implant migration. In addition to achieving biocompatibility and desirable mechanical characteristics, biomaterial implants should be optimized to avoid implant extrusion or re-herniation post-operatively. This review discusses the most commonly used testing protocols for assessing mechanical properties of biomaterial implants and serves as reference material for enabling researchers to characterize NP implants through a unified approach whereby newly developed biomaterials may be compared and contrasted to existing devices., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

At present, peripheral nerve injuries (PNIs) are one of the leading causes of substantial impairment around the globe. Complete recovery of nerve function after an injury is challenging. Currently, autologous nerve grafts are being used as a treatment; however, this has several downsides, for example, donor site morbidity, shortage of donor sites, loss of sensation, inflammation, and neuroma development. The most promising alternative is the development of a nerve guide conduit (NGC) to direct the restoration and renewal of neuronal axons from the proximal to the distal end to facilitate nerve regeneration and maximize sensory and functional recovery. Alternatively, the response of nerve cells to electrical stimulation (ES) has a substantial regenerative effect. The incorporation of electrically conductive biomaterials in the fabrication of smart NGCs facilitates the function of ES throughout the active proliferation state. This article overviews the potency of the various categories of electroactive smart biomaterials, including conductive and piezoelectric nanomaterials, piezoelectric polymers, and organic conductive polymers that researchers have employed latterly to fabricate smart NGCs and their potentiality in future clinical application. It also summarizes a comprehensive analysis of the recent research and advancements in the application of ES in the field of NGC., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

This study aimed to evaluate the Carbon Fiber obtained from PAN textile and cotton fiber in their different forms of presentation: non-activated carbon fiber felt (NACFF), activated carbon fiber felt (ACFF), silver activated carbon fiber felt (Ag-ACFF), and activated carbon fiber tissue (ACFT), to obtain scaffolds as a potential material with properties related to the synthetic bone graft. Characterization tests performed: surface wettability, traction, swelling, and in vivo tests: evaluation of the inflammatory response by implanting the materials in the subcutaneous tissue of 14 Wistar rats, evaluation of collagen fibers by picrosirius red staining and assessment of toxicity in the following organs: heart, spleen, liver, and kidney. In the wettability test, NACFF and ACFT were hydrophobic (θ124° and 114°), ACFF and Ag-ACFF were hydrophilic. For maximum stress, ACFF was more resistant (2.983 ± 1.059) p < .05. In the swelling test, the Ag-ACFF and ACFF groups showed the highest absorption percentage for the PBS solution and distilled water (p < .001). The organs showed no signs of acute systemic toxicity. The implant regions showed mild to moderate inflammatory infiltrate at 7 and 21 days. Only the ACFT group did not show the maturation of type I collagen fibers in 21 days. Through the conducted analyses, the ACFT shows little potential to be indicated as a possible scaffold. Therefore NACFF, ACFF, and Ag-ACFF have the potential to be considered scaffolds due to the following characteristics presented: good absorption rate, hydrophilicity, and non-toxic., (© 2023 Wiley Periodicals LLC.)

Cardiovascular diseases, such as myocardial infarction, are considered a significant global burden and the leading cause of death. Given the inability of damaged cardiac tissue to self-repair, cell-based tissue engineering and regeneration may be the only viable option for restoring normal heart function. To maintain the normal excitation-contraction coupling function of cardiac tissue, uniform electronic and ionic conductance properties are required. To transport cells to damaged cardiac tissues, several techniques, including the incorporation of cells into conductive polymers (CPs) and biomaterials, have been utilized. Due to the complexity of cardiac tissues, the success of tissue engineering for the damaged heart is highly dependent on several variables, such as the cell source, growth factors, and scaffolds. In this review, we sought to provide a comprehensive overview of the electro CPs and biomaterials used in the engineering and regeneration of heart tissue., (© 2023 Wiley Periodicals LLC.)

In this work, composite electrospun fibers containing innovative bioactive glass nanoparticles were produced and characterized. Poly(ε-caprolactone), benign solvents, and sol-gel B- and Cu-doped bioactive glass powders were used to fabricate fibrous scaffolds. The retention of bioactive glass nanoparticles in the polymer matrix, the electrospinnability of this novel solution and the obtained electrospun composites were extensively characterized. As a result, composite electrospun fibers characterized by biocompatibility, bioactivity, and exhibiting overall properties adequate for both hard and soft tissue engineering applications, have been produced. The addition of these bioactive glass nanoparticles was, indeed, able to impart bioactive properties to the fibers. Cell culture studies show promising results, demonstrating proliferation and growth of cells on the composite fibers. Wettability, degradation rate, and mechanical performance were also tested and are in line with previous results., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

The field of biomaterials science is highly active, with a steadily increasing number of publications and new journals being founded. This article brings together contributions from the editors of six leading journals in the area of biomaterials science and engineering. Each contributor highlights specific advances, topics, and trends that have emerged through the publications in their respective journal in the calendar year 2022. It presents a global perspective on a wide range of material types, functionalities, and applications. The highlighted topics include a diversity of biomaterials; from proteins, polysaccharides, and lipids to ceramics, metals, advanced composites, and a variety of new forms of these materials. Important advances in dynamically functional materials are presented, including a range of fabrication techniques such as bioassembly, 3D bioprinting and microgel formation. Similarly, several applications are highlighted in drug and gene delivery, biological sensing, cell guidance, immunoengineering, electroconductivity, wound healing, infection resistance, tissue engineering, and treatment of cancer. The goal of this paper is to provide the reader with both a broad view of recent biomaterials research, as well as expert commentary on some of the key advances that will shape the future of biomaterials science and engineering., (© 2023 Wiley Periodicals LLC.)

Image analysis platforms have gained increasing popularity in the last decade for the ability to automate and conduct high-throughput, multiplex, and quantitative analyses of a broad range of pathological tissues. However, imaging tissues with unique morphology or tissues containing implanted biomaterial scaffolds remain a challenge. Using HALO®, an image analysis platform specialized in quantitative tissue analysis, we have developed a novel method to determine multiple cell phenotypes in porous precision-templated scaffolds (PTS). PTS with uniform spherical pores between 30 and 40 μm in diameter have previously exhibited a specific immunomodulation of macrophages toward a pro-healing phenotype and an overall diminished foreign body response (FBR) compared to PTS with larger or smaller pore sizes. However, signaling pathways orchestrating this pro-healing in 40 μm PTS remain unclear. Here, we use HALO® to phenotype PTS resident cells and found a decrease in pro-inflammatory CD86 and an increase in pro-healing CD206 expression in 40 μm PTS compared to 100 μm PTS. To understand the mechanisms that drive these outcomes, we investigated the role of myeloid-differentiation-primary-response gene 88 (MyD88) in regulating the pro-healing phenomenon observed only in 40 μm PTS. When subcutaneously implanted in MyD88KO mice, 40 μm PTS reduced the expression of CD206, and the scaffold resident cells displayed an average larger nuclear size compared to 40 μm PTS implanted in mice expressing MyD88. Overall, this study demonstrates a novel image analysis method for phenotyping cells within PTS and identifies MyD88 as a critical mediator in the pore-size-dependent regenerative healing and host immune response to PTS., (© 2023 Wiley Periodicals LLC.)

Poly-γ-glutamic acid (PGA) is a naturally degradable hydrophilic linear microbial polymer with moisturizing, immunogenic, cross-linking, and hydrogel water absorption properties similar to hyaluronic acid, a biomaterial that is commonly used as a dermal filler. To explore the development feasibility of cross-linked PGA as a novel dermal filler, we studied the local skin response to PGA fillers and the effect of various cross-linking preparations on the average longevity of dermal injection. Injection site inflammation and the formation of collagen and elastin were also determined. PGA hydrogel particles prepared using 28% PGA and 10% 1,4-butanediol diglycidyl ether showed optimal filler properties, resistance to moist heat sterilization, and an average filling longevity of 94.7 ± 61.6 days in the dermis of rabbit ears. Local redness and swelling due to filler injection recovered within 14.2 ± 3.6 days. Local tissue necrosis or systemic allergic reactions were not observed, and local collagen formation was promoted. Preliminary results suggested that dermal injection of cross-linked PGA particles appeared safe and effective, suggesting that cross-linked PGA particles could be developed as a new hydrogel dermal filler., (© 2023 Wiley Periodicals LLC.)

Strategies to promote rapid formation of functional endothelium are required to maintain blood fluidity and regulate smooth muscle cell proliferation in synthetic vascular conduits. In this work, we explored the biofunctionalization of silk biomaterials with recombinantly expressed domain V of human perlecan (rDV) to promote endothelial cell interactions and the formation of functional endothelium. Perlecan is essential in vascular development and homeostasis and rDV has been shown to uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions, both key contributors of vascular graft failure. rDV was covalently immobilized on silk using plasma immersion ion implantation (PIII), a simple one-step surface treatment process which enables strong immobilization in the absence of chemical cross-linkers. rDV immobilization on surface-modified silk was assessed for amount, orientation, and bio-functionality in terms of endothelial cell interactions and functional endothelial layer formation. rDV immobilized on PIII-treated silk (rDV-PIII-silk) supported rapid endothelial cell adhesion, spreading, and proliferation to form functional endothelium, as evidenced by the expression of vinculin and VE-cadherin markers. Taken together, the results provide evidence for the potential of rDV-PIII-silk as a biomimetic vascular graft material., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Tissue clearing of whole intact organs has enhanced imaging by enabling the exploration of tissue structure at a subcellular level in three-dimensional space. Although clearing and imaging of the whole organ have been used to study tissue biology, the microenvironment in which cells evolve to adapt to biomaterial implants or allografts in the body is poorly understood. Obtaining high-resolution information from complex cell-biomaterial interactions with volumetric landscapes represents a key challenge in the fields of biomaterials and regenerative medicine. To provide a new approach to examine how tissue responds to biomaterial implants, we apply cleared tissue light-sheet microscopy and three-dimensional reconstruction to utilize the wealth of autofluorescence information for visualizing and contrasting anatomical structures. This study demonstrates the adaptability of the clearing and imaging technique to provide sub-cellular resolution (0.6 μm isotropic) 3D maps of various tissue types, using samples from fully intact peritoneal organs to volumetric muscle loss injury specimens. Specifically, in the volumetric muscle loss injury model, we provide 3D visualization of the implanted extracellular matrix biomaterial in the wound bed of the quadricep muscle groups and further apply computational-driven image classification to analyze the autofluorescence spectrum at multiple emission wavelengths to categorize tissue types at the injured site interacting with the biomaterial scaffolds., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

To evaluate the osteoconductive potential of inorganic biomaterials of bovine origin submitted to different temperatures in the bone repair of critical defects in rat calvaria. Forty-eight rats were divided into four groups according to the material used to fill the defect: control group (GC), the defect was filled only with blood clot (n = 12); GBO, defect filled with Bio-Oss®, deproteinzed at 300°C (n = 12); GOX, defect filled with Inorganic GenOx®, deproteinzed from 850 to 1200°C (n = 12) and G700, defect filled with Inorganic GenOx 700, deproteinzed at 700°C (n = 12). In each animal's calvaria, a trephine bur with 5 mm internal diameter was used to produce a 6 mm-diameter central defect. Gen Derm® resorbable bovine membrane was superimposed over all defects. Subsequently, animals were euthanized at 30 and 60 days after surgery. The pieces were sent for histological and histometric analysis to evaluate the following variables: bone neoformation, presence of biomaterial, mononuclear and polymorphonuclear leukocytes, presence of other tissues (granulation and medullary) and maturation of collagen fibers. The most representative group for bone neoformation was GC. At 30 days, there was a higher mean of mature bone tissue (75.8). At 60 days, there was no statistical difference between the GC (64.9), GBO (32.9), GOX (45.3), and G700 (26.6) groups. GBO presented the highest amount of biomaterial after 30 days (115.9) and 60 days (118.5). All bovine biomaterials were biocompatible and osteoconductive. GOX promoted the best bone repair of the studied materials., (© 2022 Wiley Periodicals LLC.)

A major challenge in chronic wound treatment is maintaining an appropriate wound moisture balance throughout the healing process. Wound dehydration hinders wound healing due to impeded molecule transport and cell migration with associated tissue necrosis. In contrast, wounds that produce excess fluid contain high levels of reactive oxygen species and matrix metalloproteases that impede cell recruitment, extracellular matrix reconstruction, and angiogenesis. Dressings are currently selected based on the relative amount of wound exudate with no universal dressing available that can maintain appropriate wound moisture balance to enhance healing. This work aimed to develop a high porosity poly(ethylene glycol) diacrylate hydrogel foam that can both rapidly remove exudate and provide self-tuning moisture control to prevent wound dehydration. A custom foaming device was used to vary hydrogel foam porosity from 25% to 75% by adjusting the initial air-to-solution volume ratio. Hydrogel foams demonstrated substantial improvements in water uptake volume and rate as compared to bulk hydrogels while maintaining similar hydration benefits with slow dehydration rates. The hydrogel foam with the highest porosity (~75%) demonstrated the greatest water uptake and rate, which outperformed commercial dressing products, Curafoam® and Silvercel®, in water absorption, moisture retention, and exudate management. Investigation of the water vapor transmission rates of each dressing at varied hydration levels was characterized and demonstrated the dynamic moisture-controlling capability of the hydrogel foam dressing. Overall, the self-tuning moisture control of this hydrogel foam dressing holds great promise to improve healing outcomes for both dry and exudative chronic wounds., (© 2023 Wiley Periodicals LLC.)

Graphene oxide (GO) nanosheets are a promising class of carbon-based materials suitable for application in the construction of medical devices. These materials have inherent antimicrobial properties based on sheet size, but these effects must be carefully traded off to maintain biocompatibility. Chemical modification of functional groups to the lattice structure of GO nanosheets enables unique opportunities to introduce new surface properties to bolster biological effects. Herein, we have developed nitric oxide (NO)-releasing GO nanosheets via immobilization of S-nitrosothiol (RSNO) moieties to GO nanosheets (GO-[NH] x -SNO). These novel RSNO-based GO nanosheets were characterized for chemical functionality via Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, and colorimetric assays for functional group quantification. Stoichiometric control of the available RSNO groups functionalized onto the nanosheets was studied using chemiluminescence-based NO detection methods, showing highly tunable NO release kinetics. Studies of electrical stimulation and subsequent electrochemical reduction of the nanosheets demonstrated further tunability of the NO release based on stimuli. Finally, nanosheets were evaluated for cytotoxicity and antibacterial effects, showing strong cytocompatibility with human fibroblasts in parallel to broad antibacterial and anti-biofilm effects against both Gram-positive and Gram-negative strains. In summary, derivatized GO-(NH) x -SNO nanosheets were shown to have tunable NO release properties, enabling application-specific tailoring for diverse biomedical applications such as antimicrobial coatings and composite fillers for stents, sensors, and other medical devices., (© 2023 Wiley Periodicals LLC.)

A particular challenge to the field of neuroscience involves translating findings from 2D in vitro systems to 3D in vivo environments. Standardized cell culture environments that adequately reflect the properties of the central nervous system (CNS) such as the stiffness, protein composition, and microarchitecture in which to study 3D cell-cell and cell-matrix interactions are generally lacking for in vitro culture systems. In particular, there remains an unmet need for reproducible, low-cost, high-throughput, and physiologically relevant environments comprised of tissue-native matrix proteins for the study of CNS microenvironments in 3D. Advances in the field of biofabrication over the past number of years have facilitated the production and characterization of biomaterial-based scaffolds. Typically developed for tissue engineering applications, they also provide sophisticated environments in which to study cell-cell and cell-matrix interactions and have been used for 3D modeling for a range of tissues. Here, we describe a simple and scalable protocol for the production of biomimetic, highly porous freeze-dried hyaluronic acid scaffolds with tunable microarchitecture, stiffness, and protein composition. Furthermore, we describe several different approaches that can be used to characterize a range of physicochemical properties and how to employ the scaffolds for the 3D culture of sensitive CNS cells in vitro. Finally, we detail several approaches for the study of key cell responses within the 3D scaffold environments. Overall, this protocol describes the manufacture and testing of a biomimetic and tunable macroporous scaffold system for neuronal cell culture applications. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Scaffold manufacture Basic Protocol 2: Scaffold characterization Basic Protocol 3: Cell culture and analysis of neurons in scaffolds., (© 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.)

The treatment of bone regeneration failures has been constantly improved with the study of new biomaterials. Techgraft® is a collagen membrane derived from bovine pericardium, which has been shown to have biocompatibility and effectiveness in tissue repair. However, its use in orthopedics has not yet been evaluated. Therefore, the purpose of this study was to characterize a bovine pericardium collagen membrane and evaluate the effects of its use in the regeneration of a bone defect in rat tibia. Scanning electron microscopy, atomic force microscopy, weight lost and water uptake tests, and mechanical test were performed. Afterwards, the membrane was tested in an experimental study, using 12 male Sprague Dawley rats. A bone defect was surgically made in tibiae of animals, which were assigned to two groups (n = 6): bone defect treated with collagen membrane (TG) and bone defect without treatment (CONT). Then, tibiae were submitted to micro-CT. The membranes preserved their natural collagen characteristics, presenting great strength, high water absorption, hydrophilicity, and almost complete dissolution in 30 days. In the experimental study, the membrane enhanced the growth of bone tissue in contact with its surface. A higher bone volume and trabeculae number and less trabecular space was observed in bone defects of the membrane group compared to the control group at 21 days. In conclusion, the Techgraft membrane seems to have favorable characteristics for treatment of long bone repair., (© 2022 Wiley Periodicals LLC.)

The objective was to synthesize and characterize fine polycaprolactone (PCL) fibers associated with a new 58S bioglass obtained by the precipitated sol-gel route, produced by the electrospinning process in order to incorporate therapeutic ions (Mg and Li). In PCL/acetone solutions were added 7% pure bioglass, bioglass doped with Mg(NO 3 ) 2 and Li 2 CO 3 and were subjected to electrospinning process. The fibers obtained were characterized morphologically, chemically and biologically. The results showed the presence of fine fibers at the nanometric scale and with diameters ranging from 0.67 to 1.92 μm among groups. Groups containing bioglass showed particles both inside and on the surface of the fibers. The components of the polymer, bioglass and therapeutic ions were present in the fibers produced. The produced fibers showed cell viability and induced the formation of mineralization nodules. It was observed the applicability of that methodology in making an improved biomaterial, which adds the osteoinductive properties of the bioglass to PCL and to those of therapeutic ions, applicable to guided bone regeneration., (© 2022 Wiley Periodicals LLC.)

A novel low volume blood loop model (Ension Triad System [ETS]) incorporating pulsatile flow and a proprietary low-activation blood-contacting surface (Ension bioactive surface [EBS]) enabling high signal-to-noise performance is described. The ETS system incorporates a test chamber that allows direct comparison of material samples or finished medical devices such as catheters with varying compositions and/or surface treatments. ETS performance is presented from two independent organizations (Medtronic and MLM Labs) and includes results for hemolysis (pfHgb), platelet count, platelet activation (βTG), coagulation (TAT), inflammation (PMN Elastase, PMN CD112b, and monocyte CD112b) and immune response (SC5b-9) were made on: (1) the EBS-treated system itself without a test material (No Material, NM); (2) the EBS-treated system with an idealized untreated catheter (UC); and (3) the EBS-treated system with the prototype catheter treated with the EBS surface treatment (CC). The untreated catheter (UC) was associated with significant elevation of all activation marker levels (pfHgb excluded). The EBS-treated catheter, in direct comparison to the UC and NM catheters, appeared invisible with respect to the activation markers (all markers statistically different than the UC and equivalent to the NM control). Based on these data, we conclude that using a relatively small surface area test sample and a small volume of fresh human blood, the high signal-to-noise performance of the ETS system demonstrates comprehensive and statistically significant material differences in the major ISO 10993-4 categories of blood interaction. These data underscore the important benefit of minimal confounding of test/device responses with non-test-material/model-related responses. ETS offers a practical alternative to the common one-test-category-at-a-time approach when assessing blood/medical device interactions., (© 2022 Wiley Periodicals LLC.)

This study aims to evaluate the potential of a novel biomaterial synthesized from amorphous calcium phosphate (ACP), octacalcium phosphate (OCP), and hydroxyapatite (HA) to repair critical-sized defects (CSD) in rabbit calvaria. In vitro analyses of cell viability, cell proliferation, formation of mineral nodules, and cell differentiation using qPCR were performed for comparing experimental calcium phosphate (ECP), deproteinized bovine bone (DBB), and beta-tricalcium phosphate (β-TCP). Bilateral CSDs were created in 45 rabbit calvaria. Six groups were evaluated: ECP, ECP + fibrin sealant (ECP + S), coagulum, autogenous bone, DBB, and β-TCP. Euthanasia was performed at 2, 4, and 8 weeks, followed by micro-computed tomography and histological and immunohistochemical analyses. Results from in vitro analyses revealed similar biocompatibility for all tested materials and a tendency for higher gene expression of some bone markers in the ECP group than in β-TCP and DBB groups at 7 days. In contrast to that in DBB and β-TCP groups, ECP displayed growing bone volume over total volume percentage (BV/TV%) with time in vivo. Histological analysis revealed a greater number of giant cells and reduced size of grafted particles in ECP during all periods of analysis. RUNX-2 expression was statistically lower in ECP than DBB at 2 and 4 weeks. Despite no statistical significance, ECP presented the highest absolute values for ALP-expression at 2, 4, and 8 weeks compared with other groups. Together, our findings indicate that a combination of the ACP, OCP, and HA phases into ECP is beneficial and promising for bone regeneration., (© 2022 Wiley Periodicals LLC.)

Stress urinary incontinence (SUI) impacts ~1/3 of women over age 50. Negative publicity around PP meshes used in pelvic prolapse repair drives the need for identifying alternative biomaterials for SUI repair. Our study evaluated in vivo response to collagen sling implanted in an ovine model. Electrocompacted collagen threads were filament wound as slings and crosslinked in genipin. Collagen slings were implanted suburethrally mimicking the transvaginal tape technique. Main study groups were: Collagen sling (n = 3, 6 months) and PP sling (n = 3, 6 months). Collagen sling was also tested at 3-weeks (n = 1) to observe early-stage tissue response and 1-year (n = 2) to assess biomaterial longevity in a preliminary capacity. Collagen slings healed to a fibrous ligament texture at 6 months and maintained such texture to 1 year. Histological scoring indicated biocompatible responses to collagen slings with no adverse events. All study groups exhibited complete tissue ingrowth and interstitial de novo collagen deposition at all time points. Collagen threads induced orderly de novo collagen deposition that was aligned along long axes of threads. Tissue infiltrated collagen slings that were explanted at 6 and 12 months presented similar structural strength with native tissues such as vagina and fascia, and PP (Lynx) slings (p > .05). With the limitation of low number of animals per time point in hindsight, this preliminary study justifies evaluation of collagen slings in a larger sample size of animals, particularly to assess persistence of ligamentous tissue response over longer durations than 1-year., (© 2022 Wiley Periodicals LLC.)

Important processes related to the interaction of the oral microbiome with the tooth surface happen directly at the interface. For example, the chemical microenvironment that exists at the interface of microbial biofilms and the native tooth structure is directly involved in caries development. Consequentially, a critical understanding of this interface and its chemical microenvironment would provide novel avenues in caries prevention, including secondary caries that often occurs at the interface of the dental biofilm, tooth structure, and dental material. Electrochemical sensors are a unique quantitative tool and have the inherent advantages of miniaturization, stability, and selectivity. That makes the electrochemical sensors ideal tools for studying these critical biofilm microenvironments with high precision. This review highlights the development and applications of several novel electrochemical sensors such as pH, Ca 2+ , and hydrogen peroxide sensors as scanning electrochemical microscope probes in addition to flexible pH wire sensors for real-time bacterial biofilm-dental surface and dental materials interface studies., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Nitinol (NiTi), a nickel-titanium alloy, has been used for various cardiovascular, orthopedic, fracture fixation, and orthodontic devices. As with most other metallic biomaterials, the corrosion resistance and biocompatibility of NiTi are primarily determined by the properties of the surface oxide layer such as thickness, chemical composition, structure, uniformity, and stability. Currently, a number of finishing methods are used to improve the properties of surface oxide of NiTi with an ultimate goal to produce a defect-free, impurity-free, thin homogeneous oxide layer that is stable and composed of only titanium dioxide (TiO 2 ) with negligible amount of Ni species. This review discusses the effects of various surface finishing methods such as mechanical polishing, electropolishing, magnetoelectropolishing, heat treatments at different temperatures, passivation, chemical etching, boiling in water, hydrogen peroxide treatment, and sterilization techniques (steam autoclave, ethylene oxide, dry heat, peracetic acid, and plasma-based treatments) on the properties of a surface oxide layer and how it impacts the corrosion resistance of NiTi. Considering the findings of the literature review, a checklist has been provided to assist with choosing finishing/sterilization methods and relevant rationale and recommendations to consider when selecting a surface finishing process for NiTi used in implantable medical devices., (© 2022 Wiley Periodicals LLC.)

Hydroxyapatite (HAp) constitutes a significant inorganic compound which due to its osteoinductivity, osteoconductivity as well as the ability to promote bone growth and regeneration is widely applied in development of biomaterials designed for bone tissue engineering. In this work, various synthesis methodologies of HAp based on the wet precipitation technique were applied, and the impact of pH of the reaction mixture, the concentration of individual reagents as well as the type of stirring applied (mechanical/magnetic) on the properties of final powders was discussed. Spectroscopic methods (Fourier transform infrared, Raman) and X-ray diffraction allowed to verify the synthesis parameters leading to obtaining calcium phosphate with 96% HAp in phase which indicated higher homogeneity of obtained powder (93.4%) than commercial HAp. Powders' morphology was evaluated using microscopic techniques while specific surface area was determined via Brunauer-Emmett-Teller analysis. Particle size distribution, porosity of powders, and stability of HAp suspensions were also characterized. It was proved that synthesis at pH = 11.0 using mechanical stirring resulted in calcium phosphate with a high phase homogeneity and homogeneous pore size distribution (6-20 nm). Moreover, obtained HAp powder showed 71.8% more specific surface area than commercial material-that is, 110 m 3 /g for synthetic HAp and 64 m 3 /g in the case of commercial powder-which, in turn, is significant in terms of its potential application as carrier of active substances. Thus it was demonstrated that by applying appropriate conditions of HAp synthesis it is possible to obtain powder with properties enhancing its application potential for medical purposes., (© 2022 Wiley Periodicals LLC.)

Engineering skin substitutes represent a prospective source of advanced therapy in repairing severe traumatic wounds. Sodium alginate (SA) and silk fibroin (SF) are natural biomaterials, which are widely used in tissue engineering and other fields because of their low price, high safety, and good biocompatibility. However, SA itself degrades slowly, its degradation mode is difficult to control, and the degradation products are difficult to remove from the body because of its high molecular weight. Therefore, the composite scaffolds were prepared by freeze-drying composite technology by using the Schiff base reaction between biocompatible SF and permeable oxidized sodium alginate (OSA). Sodium periodate was used as oxidant to modify SA. The results showed that higher oxidation degree of OSA could be obtained by increasing the proportion of oxidant, and the relative molecular weight of the oxidized products could also be reduced. The composite scaffolds were prepared by using sodium tetraborate as a crosslinking accelerator of the Schiff base reaction between OSA and SF. FT-IR confirmed that the Schiff base group appeared in the material. In vitro biodegradation experiments showed that the biodegradation of the composite scaffolds was controllable, and the cytocompatibility experiment showed that the composite scaffolds had good biocompatibility., (© 2022 Wiley Periodicals LLC.)

In the context of regenerative endodontics research with the development of biomaterials, this work aimed to develop and test a prototype biomimetic bioreactor of a human tooth. The bioreactor was designed to reproduce a shaped dental canal connected with a cavity reproducing the periapical region and irrigated through two fluidic channels intended to reproduce the apical residual vascular supply. A test biomaterial composed of polylactic acid/polycaprolactone-tannic acid (PLA/PCL-TA) was produced by electrospinning/electrospraying and calibrated to be inserted in a dental canal. This biomaterial was first used to evaluate its imbibition capacity and the oximetry inside the bioreactor. Then, Dental Pulp Stem Cells (DPSCs) were cultured on PLA/PCL-TA cones for 1-3 weeks in the bioreactor; afterward cell adhesion, proliferation, and migration were histologically assessed. Complete imbibition biomaterial was obtained in 10 min and oximetry was stable over time. In the bioreactor, DPSCs were able to adhere, proliferate and migrate onto the surface and inside the biomaterial. In conclusion, this bioreactor was used successfully to test a biomaterial intended to support pulp regeneration and constitutes a new in vitro experimental model closer to clinical reality., (© 2022 John Wiley & Sons Ltd.)

Guided tissue regeneration (GTR) membranes play a vital role in periodontal surgery. Recently a series of composite electrospun membranes have been fabricated to improve the unexpected biodegradation of collagen-based GTR membranes. However, their tissue integrity needs to be studied in depth. In this study, a bi-layered electrospun membrane (BEM) inspired by "prodrug" was fabricated, which contained a dense-layer (BEM-DL) and a potential loose-layer (BEM-LL). The nanofibers of BEM-DL were composed of poly(l-lactic-co-glycolic acid) and tilapia skin collagen (TSC). Whereas the BEM-LL consisted of two types of nanofibers, one was the same as BEM-DL and the other was made from TSC. The morphology, degradation in vitro, cytocompatibility and biocompatibility in rats were investigated with a poly(lactic-co-glycolic acid) electrospun membrane (PLGA) as the negative control. The pore size of BEM-LL soaked for 7 days became larger than the original sample (164.8 ± 90.9 and 52.5 ± 21.0 μm 2 , respectively), which was significantly higher (p < .05) than that of BEM-DL and PLGA. The BEM-LL displayed a larger weight loss rate of 82.3 ± 3.6% than the BEM-DL of 46.0 ± 2.8% at day 7 because of the rapid degradation of TSC fibers. The cytocompatibility test demonstrated that L929 cells were only spread on the surface of the BEM-DL while MC3T3-E1 cells grew into the BEM-LL layer. The subcutaneous implantation test further proved that BEM-DL performed as a cellular barrier, whereas BEM-LL was conducive to cell infiltration as deep as 200 μm with reduced fibrous encapsulation. Herein, the BEM inspired by "prodrug" is a promising GTR membrane with a property of enhanced tissue integration., (© 2022 Wiley Periodicals LLC.)

Memory B cells originate in response to antigenic stimulation in B-cell follicles of secondary lymphoid organs where naive B cells undergo maturation within a subanatomical microenvironment, the germinal centers. The understanding of memory B-cell immunology and its regulation is based primarily on sophisticated experiments that involve mouse models. To date, limited evidence exists on whether memory B cells can be successfully engineered ex vivo, specifically using biomaterials-based platforms that support the growth and differentiation of B cells. Here, we report the characterization of a recently reported maleimide-functionalized poly(ethylene glycol) (PEG) hydrogels as immune organoids towards the development of early memory B-cell phenotype and germinal center-like B cells. We demonstrate that the use of interleukin 9 (IL9), IL21, and bacterial antigen presentation as outer membrane-bound fragments drives the conversion of naive, primary murine B cells to early memory phenotype in ex vivo immune organoids. These findings describe the induction of early memory B-cell-like phenotype in immune organoids and highlight the potential of synthetic organoids as a platform for the future development of antigen-specific bona fide memory B cells for the study of the immune system and generation of therapeutic antibodies., (© 2022 Wiley Periodicals LLC.)

Early explorations of tissue engineering and regenerative medicine concepts commonly utilized simple polyesters such as polyglycolide, polylactide, and their copolymers as scaffolds. These biomaterials were deemed clinically acceptable, readily accessible, and provided processability and a generally known biological response. With experience and refinement of approaches, greater control of material properties and integrated bioactivity has received emphasis and a broadened palette of synthetic biomaterials has been employed. Biodegradable polyurethanes (PUs) have emerged as an attractive option for synthetic scaffolds in a variety of tissue applications because of their flexibility in molecular design and ability to fulfill mechanical property objectives, particularly in soft tissue applications. Biodegradable PUs are highly customizable based on their composition and processability to impart tailored mechanical and degradation behavior. Additionally, bioactive agents can be readily incorporated into these scaffolds to drive a desired biological response. Enthusiasm for biodegradable PU scaffolds has soared in recent years, leading to rapid growth in the literature documenting novel PU chemistries, scaffold designs, mechanical properties, and aspects of biocompatibility. Despite the enthusiasm in the field, there are still few examples of biodegradable PU scaffolds that have achieved regulatory approval and routine clinical use. However, there is a growing literature where biodegradable PU scaffolds are being specifically developed for a wide range of pathologies and where relevant pre-clinical models are being employed. The purpose of this review is first to highlight examples of clinically used biodegradable PU scaffolds, and then to summarize the growing body of reports on pre-clinical applications of biodegradable PU scaffolds., (© 2022 Wiley Periodicals LLC.)

Over the past few decades, the field of biomaterials concerning bone tissue engineering has gained a significant amount of interest. This has led to new biomaterials to be used as bone substitute materials. Despite the rapid increase in the types and forms of bone substitutes, a comprehensive classification encompassing all types of bone graft materials that have so far been developed and evaluated is lacking. Therefore, this review aims to integrate and bring together the published data on bone substitutes within the last 5 years and produce a novel classification that would provide bone material researchers with a better understanding of what materials have so far been used and evaluated and the areas, where research is lacking and deserves more attention. The literature available in all major databases was obtained and filtered using an elimination criterion to extract all the articles related to studies that tested bone substitute materials in nonclinical and clinical trials over the last 5 years. The review article would provide bone material researchers with an insight into the materials that have been evaluated for bone tissue engineering applications and identify future perspectives for bone graft material research., (© 2022 Wiley Periodicals LLC.)