Biomaterials-assisted cancer vaccine delivery: preclinical landscape, challenges, and opportunities.

INTRODUCTION: Cancer vaccines (protein and peptide, DNA, mRNA, and tumor cell) have achieved remarkable success in the treatment of cancer. In particular, advances in the design and manufacture of biomaterials have made it possible to control the presentation and delivery of vaccine components to immune cells. AREAS COVERED: This review summarizes findings from major databases, including PubMed, Scopus, and Web of Science, focusing on articles published between 2005 and 2024 that discuss biomaterials in cancer vaccine delivery. EXPERT OPINION: The development of cancer vaccines is hindered by several bottlenecks, including low immunogenicity, instability of vaccine components, and challenges in evaluating their clinical efficacy. To transform preclinical successes into viable treatments, it is essential to pursue continued innovation, collaborative research, and address issues related to scalability, regulatory pathways, and clinical validation, ultimately improving outcomes against cancer.

Bioprocessing of human platelet concentrates to generate lysates and extracellular vesicles for therapeutic applications.

This work describes protocols for preparing specific forms of human platelet lysates from pooled platelet concentrates (PCs) and the isolation of platelet-derived extracellular vesicles (p-EVs). Clinical-grade PCs can be sourced from blood establishments immediately following expiration for transfusion use. Here, we describe methods to process PCs into specific lysates from which p-EVs can be isolated. Each lysate type is prepared using platelet activation and processing methods which produce distinct products that may be useful in different applications. For example, serum-converted platelet lysate (SCPL)-EVs were recently shown to have powerful therapeutic properties following myocardial infarction in mice. EVs can be isolated from all products using size exclusion chromatography, producing pure and consistent p-EVs from multiple batches. Together, these methods allow isolation of p-EVs with excellent potential for clinical and preclinical applications.•Platelet concentrates (PCs) obtained from local blood establishments are reliable and sustainable sources to generate biomaterials.•We outline five distinct methods of platelet lysate generation and one method for extracellular vesicle isolation.•Each platelet lysate form has different biological properties which may be suitable for certain applications.

An Evaluation of the Replacement of Animal-derived Biomaterials in Human Primary Cell Culture.

The likelihood that potential new drugs will successfully navigate the current translational pipeline is poor, with fewer than 10% of drug candidates making this transition successfully, even after their entry into clinical trials. Prior to this stage, candidate drugs are typically evaluated by using models of increasing complexity, beginning with basic in vitro cell culture studies and progressing through to animal studies, where many of these candidates are lost due to lack of efficacy or toxicology concerns. There are many reasons for this poor translation, but interspecies differences in functional and physiological parameters undoubtedly contribute to the problem. Improving the human-relevance of early preclinical in vitro models may help translatability, especially when targeting more nuanced species-specific cell processes. The aim of the current study was to define a set of guidelines for the effective transition of human primary cells of multiple lineages to more physiologically relevant, translatable, animal-free in vitro culture conditions. Animal-derived biomaterials (ADBs) were systematically replaced with non-animal-derived alternatives in the in vitro cell culture systems, and the impact of the substitutions subsequently assessed by comparing the kinetics and phenotypes of the cultured cells. ADBs were successfully eliminated from primary human dermal fibroblast, uterine fibroblast, pulmonary fibroblast, retinal endothelial cell and peripheral blood mononuclear cell culture systems, and the individual requirements of each cell subtype were defined to ensure the successful transition toward growth under animal-free culture conditions. We demonstrate that it is possible to transition ('humanise') a diverse set of human primary cell types by following a set of simple overarching principles that inform the selection, and guide the evaluation of new, improved, human-relevant in vitro culture conditions.

Xeno Nucleic Acids as Functional Materials: From Biophysical Properties to Application.

Xeno nucleic acid (XNA) are artificial nucleic acids, in which the chemical composition of the sugar moiety is changed. These modifications impart distinct physical and chemical properties to XNAs, leading to changes in their biological, chemical, and physical stability. Additionally, these alterations influence the binding dynamics of XNAs to their target molecules. Consequently, XNAs find expanded applications as functional materials in diverse fields. This review provides a comprehensive summary of the distinctive biophysical properties exhibited by various modified XNAs and explores their applications as innovative functional materials in expanded fields.

Characterization of Calotropis gigantiea plant leaves biomass-based bioplasticizers for biofilm applications.

The present surge in environmental consciousness has pushed for the use of biodegradable plasticizers, which are sustainable and abundant in plant resources. As a result of their biocompatibility and biodegradability, Calotropis gigantiea leaf plasticizers (CLP) serve as viable alternatives to chemical plasticizers. First time, the natural plasticizers from the Calotropis leaves were extracted for this study using a suitable chemical approach that was also environmentally friendly. The XRD results showed a reduced crystallinity index of 20.2 % and a crystalline size of 5.3 nm, respectively. TGA study revealed that the CLP has good thermal stability (244 °C). Through FT-IR study, the existence of organic compounds in CLP can be investigated by key functional groups such as alcohol, amine, amide, hydrocarbon, alkene, aromatic, etc. Further the presence of alcoholic, amino, and carboxyl constituents was confirmed by UV investigation. SEM, EDAX analysis, and AFM are used to examine the surface morphology of the isolated plasticizer. SEM pictures reveal rough surfaces on the CLP surface pores, which makes them suitable for plasticizing new bioplastics with improved mechanical properties. Poly (butylene adipate-co-terephthalate) (PBAT), a biodegradable polymer matrix, was used to investigate the plasticization impact after the macromolecules were characterised. The biofilm PBAT/CLP had a thickness of 0.8 mm. In addition, the reinforcement interface was examined using scanning electron microscopy. When CLP is loaded differently in PBAT, the tensile strength and young modulus change from 15.30 to 24.60 MPa and from 137 to 168 MPa, respectively. CLP-reinforced films demonstrated better surface compatibility and enhanced flexibility at a loading of 2 % when compared to pure PBAT films. Considering several documented characteristics, CLP may prove to be an excellent plasticizer for resolving environmental issues in the future.

Region-Specific Decellularization of Porcine Uterine Tube Extracellular Matrix: A New Approach for Reproductive Tissue-Engineering Applications.

The uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which is directly associated to its functions. Considering this, the application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. The decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed the ECM composition and structure by optical and scanning electronic microscopy, FTIR, and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting a significative reduction in cellular content. Structural and spectroscopy analyses revealed that the produced scaffolds remained well structured and with the ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing high cell viability rates and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

Advances in Extraction, Structure, and Physiochemical Properties of Sorghum Kafirin for Biomaterial Applications: A Review.

Kafirin is an endosperm-specific hydrophobic protein found in sorghum grain and the waste by-product from sorghum biorefineries known as sorghum dried distillers' grain with solubles (DDGS). Because of kafirin's poor nutritional profile (negative nitrogen balance, slow digestibility, and lack of some essential amino acids), its direct human use as a food is restricted. Nevertheless, increased focus on biofuel production from sorghum grain has triggered a new wave of research to use sorghum DDGS kafirin as a food-grade protein for biomaterials with diverse applications. These applications result from kafirin's unique chemical nature: high hydrophobicity, evaporation-induced self-assembling capacity, elongated conformation, water insolubility, and low digestibility. Aqueous alcohol mixtures have been widely used for the extraction of kafirin. The composition, structure, extraction methodologies, and physiochemical properties of kafirin, emphasising its biomaterial functionality, are discussed in detail in this review. The literature survey reveals an in-depth understanding of extraction methodologies and their impact on structure functionality, which could assist in formulating materials of kafirin at a commercial scale. Ongoing research continues to explore the potential of kafirin and optimise its utilisation as a functional biomaterial, highlighting its valuable structural and physicochemical properties. Further studies should focus on covering gaps in the research as some of the current structural understanding comes from data on zein protein from maize.

Food waste generation and its industrial utilization: An overview.

Food waste is produced for intended human consumption and is normally lost, discharged, contaminated, or finally degraded. The rising problem of food waste is increasing rapidly, so every sector is involved in minimizing food waste generation as well as waste management from collection to disposal, and scientists are developing the best eco-friendly and sustainable solutions for all sectors in the food supply chain, from the agricultural sector to the industrial sector and even up to the retailer to human consumption. Sustainable management is needed for the food wastes in the agricultural and industrial sectors, which are a major burning headache for environmentalists, health departments, and the government all over the earth. Various strategies can be employed to effectively control food waste, and these strategies can be ranked in a manner similar to the waste management hierarchy. The most desirable options involve the act of avoiding and donating edible portions to social agencies. Food waste is utilized in industrial operations to produce biofuels or biopolymers. The next stages involve the retrieval of nutrients and the sequestration of carbon through composting. The government implements appropriate management practices, laws, and orders to minimize food waste generation. Different contemporary methods are utilized to produce biofuel utilizing various types of food waste. In order for composting techniques to recover nutrients and fix carbon, food waste must be processed. Both the management of food waste and the creation of outgrowths utilizing biomaterials require additional study. This review aims to present a comprehensive analysis of the ongoing discourse surrounding the definitions of food waste, the production and implementation of methods to reduce it, the emergence of conversion technologies, and the most recent trends.

Bioprinting Cell-Laden Hydrogels for Studies of Epithelial Tissue Morphogenesis.

The extracellular matrix (ECM) provides dynamic structural and molecular signals that affect the form and function of developing tissues. In order to parse how the individual features of the ECM impact cell- and tissue-level behavior during development, engineered culture models should reproduce key structural and molecular features of native ECM. Here, we describe a protocol for bioprinting epithelial cell aggregates embedded within a collagen-Matrigel ink in order to study the dynamic interplay between epithelial tissues and aligned networks of type I collagen fibers. Collagen fiber alignment and geometry can be spatially controlled by modulating the printing speed, nozzle geometry, surface chemistry, and degree of molecular crowding in the printing ink. We provide detailed procedures for generating epithelial cell aggregates, microextrusion printing collagen-Matrigel bioinks, culturing the three-dimensional (3D)-printed tissues, and imaging 3D-printed collagen-Matrigel constructs.

Discovering the nucleus in a world of biomaterials.

The nucleus serves as the central hub for cellular activity, driving cell identity and behavior. Despite its crucial role, understanding how biomaterials influence the nucleus remains an underexplored area of research. In our opinion, this is an overlooked opportunity, particularly in regenerative medicine - a field where cellular control is not just beneficial, but essential. As such, we emphasize the need to recognize nuclear characteristics as a key metric for evaluating material functionality. In this leading opinion article, we discuss how state-of-the-art technologies can help reveal biomaterial-driven nuclear alterations, offering crucial insights that will advance the field of regenerative medicine.

3D printing tissue-engineered scaffolds for auricular reconstruction.

Congenital microtia is the most common cause of auricular defects, with a prevalence of approximately 5.18 per 10,000 individuals. Autologous rib cartilage grafting is the leading treatment modality at this stage of auricular reconstruction currently. However, harvesting rib cartilage may lead to donor site injuries, such as pneumothorax, postoperative pain, chest wall scarring, and deformity. Therefore, in the pursuit of better graft materials, biomaterial scaffolds with great histocompatibility, precise control of morphology, non-invasiveness properties are gradually becoming a new research hotspot in auricular reconstruction. This review collectively presents the exploit and application of 3D printing biomaterial scaffold in auricular reconstruction. Although the tissue-engineered ear still faces challenges before it can be widely applied to patients in clinical settings, and its long-term effects have yet to be evaluated, we aim to provide guidance for future research directions in 3D printing biomaterial scaffold for auricular reconstruction. This will ultimately benefit the translational and clinical application of cartilage tissue engineering and biomaterials in the treatment of auricular defects.

De Novo Design of Integrin α5ß1 Modulating Proteins for Regenerative Medicine.

Integrin α5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and α5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5ß1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5ß1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.

Three-Dimensional-Printed Modular Titanium Alloy Plates for Osteosynthesis of the Jawbone.

BACKGROUNDS: The titanium-aluminum-vanadium alloy (Ti-6Al-4V) is frequently used in implantology due to its biocompatibility. The use of 3D printing enables the mechanical modification of implant structures and the adaptation of their shape to the specific needs of individual patients. METHODS: The titanium alloy plates were designed using the 3D CAD method and printed using a 3D SLM printer. Qualitative tests were performed on the material surface using a microcomputed tomography scanner. The cytotoxicity of the modular titanium plates was investigated using the MTT assay on the L929 cell line and in direct contact with Balb/3T3 cells. Cell adhesion to the material surface was evaluated with hFOB1.19 human osteoblasts. Microbial biofilm formation was investigated on strains of Lactobacillus rhamnosus, Staphylococcus epidermidis, Streptococcus mutans and Candida albicans using the TTC test and scanning electron microscopy (SEM). RESULTS: The surface analysis showed the hydrophobic nature of the implant. The study showed that the titanium plates had no cytotoxic properties. In addition, the material surface showed favorable properties for osteoblast adhesion. Among the microorganisms tested, the strains of S. mutans and S. epidermidis showed the highest adhesion capacity to the plate surface, while the fungus C. albicans showed the lowest adhesion capacity. CONCLUSIONS: The manufactured modular plates have properties that are advantageous for the implantation and reduction in selected forms of microbial biofilm. Three-dimensional-printed modular titanium plates were investigated in this study and revealed the potential clinical application of this type of materials, regarding lack of cytotoxicity, high adhesion properties for osteoblasts and reduction in biofilm formation. The 3D CAD method allows us to personalise the shape of implants for individual patients.

Protective Encapsulation of a Bioactive Compound in Starch-Polyethylene Glycol-Modified Microparticles: Degradation Analysis with Enzymes.

Starch is a promising polymer for creating novel microparticulate systems with superior biocompatibility and controlled drug delivery capabilities. In this study, we synthesized polyethylene glycol (PEG)-modified starch microparticles and encapsulated folic acid using a solvent-mediated acid-base precipitation method with magnetic stirring, which is a simple and effective method. To evaluate particle degradation, we simulated physiological conditions by employing an enzymatic degradation approach. Our results with FTIR and SEM confirmed the successful synthesis of starch-PEG microparticles encapsulating folic acid. The average size of starch microparticles encapsulating folic acid was 4.97 µm and increased to 6.01 µm upon modification with PEG. The microparticles were first exposed to amylase at pH 6.7 and pepsin at pH 1.5 at different incubation times at physiological temperature with shaking. Post-degradation analysis revealed changes in particle size and morphology, indicating effective enzymatic degradation. FTIR spectroscopy was used to assess the chemical composition before and after degradation. The initial FTIR spectra displayed characteristic peaks of starch, PEG, and folic acid, which showed decreased intensities after enzymatic degradation, suggesting alterations in chemical composition. These findings demonstrate the ongoing development of starch-PEG microparticles for controlled drug delivery and other biomedical applications and provide the basis for further exploration of PEG-starch as a versatile biomaterial for encapsulating bioactive compounds.

Improving the hemocompatibility of a porohyperelastic layered vascular graft using luminal reversal microflows.

Vascular graft thrombosis is a long-standing clinical problem. A myriad of efforts have been devoted to reducing thrombus formation following bypass surgery. Researchers have primarily taken a chemical approach to engineer and modify surfaces, seeking to make them more suitable for blood contacting applications. Using mechanical forces and surface topology to prevent thrombus formation has recently gained more attention. In this study, we have designed a bilayered porous vascular graft capable of repelling platelets and destabilizing absorbed protein layers from the luminal surface. During systole, fluid penetrates through the graft wall and is subsequently ejected from the wall into the luminal space (Luminal Reversal Flow - LRF), pushing platelets away from the surface during diastole. In-vitro hemocompatibility tests were conducted to compare platelet deposition in high LRF grafts with low LRF grafts. Graft material properties were determined and utilized in a porohyperelastic (PHE) finite element model to computationally predict the LRF generation in each graft type. Hemocompatibility testing showed significantly lower platelet deposition values in high versus low LRF generating grafts (median±IQR = 5,708 ± 987 and 23,039 ± 3,310 platelets per mm2, respectively, p=0.032). SEM imaging of the luminal surface of both graft types confirmed the quantitative blood test results. The computational simulations of high and low LRF generating grafts resulted in LRF values of -10.06 µm/s and -2.87 µm/s, respectively. These analyses show that a 250% increase in LRF is associated with a 75.2% decrease in platelet deposition. PHE vascular grafts with high LRF have the potential to improve anti-thrombogenicity and reduce thrombus-related post-procedure complications. Additional research is required to overcome the limitations of current graft fabrication technologies that further enhance LRF generation.

Cryotherapy in the Management of Vital Pulp: A Case Report.

Cryotherapy in vital pulp treatment is a procedure that involves the use of extreme cold temperatures to manage inflammation and promote healing in the dental pulp tissue. It has shown potential in preserving pulp vitality and reducing post-operative discomfort in procedures such as partial and full pulpotomy. Vital pulp therapy (VPT) aims to preserve the vitality and function of the dental pulp. With the proper diagnosis, technique, and materials, it can effectively treat moderately inflamed pulp and minimize the need for more invasive procedures. This article presents a case of vital pulp cryotherapy in a patient having moderately inflamed pulp.

Mass Spectrometry of Collagen-Containing Allogeneic Human Bone Tissue Material.

The current paper highlights the active development of tissue engineering in the field of the biofabrication of living tissue analogues through 3D-bioprinting technology. The implementation of the latter is impossible without important products such as bioinks and their basic components, namely, hydrogels. In this regard, tissue engineers are searching for biomaterials to produce hydrogels with specified properties both in terms of their physical, mechanical and chemical properties and in terms of local biological effects following implantation into an organism. One of such effects is the provision of the optimal conditions for physiological reparative regeneration by the structural components that form the basis of the biomaterial. Therefore, qualitative assessment of the composition of the protein component of a biomaterial is a significant task in tissue engineering and bioprinting. It is important for predicting the behaviour of printed constructs in terms of their gradual resorption followed by tissue regeneration due to the formation of a new extracellular matrix. One of the most promising natural biomaterials with significant potential in the production of hydrogels and the bioinks based on them is the polymer collagen of allogeneic origin, which plays an important role in maintaining the structural and biological integrity of the extracellular matrix, as well as in the morphogenesis and cellular metabolism of tissues, giving them the required mechanical and biochemical properties. In tissue engineering, collagen is widely used as a basic biomaterial because of its availability, biocompatibility and facile combination with other materials. This manuscript presents the main results of a mass spectrometry analysis (proteomic assay) of the lyophilized hydrogel produced from the registered Lyoplast® bioimplant (allogeneic human bone tissue), which is promising in the field of biotechnology. Proteomic assays of the investigated lyophilized hydrogel sample showed the presence of structural proteins (six major collagen fibers of types I, II, IV, IX, XXVII, XXVIII were identified), extracellular matrix proteins, and mRNA-stabilizing proteins, which participate in the regulation of transcription, as well as inducer proteins that mediate the activation of regeneration, including the level of circadian rhythm. The research results offer a new perspective and indicate the significant potential of the lyophilized hydrogels as an effective alternative to synthetic and xenogeneic materials in regenerative medicine, particularly in the field of biotechnology, acting as a matrix and cell-containing component of bioinks for 3D bioprinting.