Microalgae are microscopic unicellular organisms that inhabit marine, freshwater, and moist terrestrial ecosystems. The vast number and diversity of microalgal species provide a significant reservoir of biologically active compounds, highly promising for biomedical applications. Diatoms are unicellular eukaryotic algae belonging to the class Bacillariophyceae. They possess intricately structured silica-based cell walls, which contain long-chain polyamines that play important roles in the formation of silica. Long-chain polyamines are uncommon polyamines found only in organisms that produce biosilica. Diatomite, which is a marine sediment of the remains of the silica skeleton of diatoms, could be an abundant source of biogenic silica that can easily be converted to silica particles. This concise review focuses on the biofabrication of polyamine-based nanosilica from diatoms and highlights the possibility of utilizing diatom biosilica as a nanocarrier for drug and siRNA delivery, bioimaging, and bone tissue engineering. The challenges that may affect diatom production, including environmental stresses and climate change, are discussed together with the prospect of increasing diatom-based biosilica production with the desired nanostructures via genetic manipulation.

Marine-derived biomaterials are emerging as promising candidates for tissue regeneration due to their sustainability, biocompatibility, bioactivity, and unique chemical structure. This review provides an overview of different marine-derived inorganic and organic materials, such as calcium carbonate, magnesium salts, silica, polysaccharides, bioactive peptides, and lipid-based compounds, and their effects in promoting osteogenesis. Specifically, the osteoinductive, osteoconductive, and osteointegrative activities of traditional and innovative materials that influence key molecular pathways such as BMP/Smad and Wnt/β-catenin signaling underlying bone formation will be evaluated. This review also prospects innovative approaches, i.e., phage display technology, to optimize marine-derived peptides for targeted bone regeneration. In the context of innovative and sustainable materials, this review suggests some interesting applications of unusual materials able to overcome the limitations of conventional ones and stimulate cellular regeneration of bone tissue by activating specific molecular pathways.

A variety of cell types and chemical systems are known to interact throughout the complex process of wound healing. In addition to being very uncomfortable for patients, wounds that do not heal properly or become chronic can place a heavy burden on society. The creation of novel treatment approaches can expedite the healing process, reduce the societal burden, and improve patient outcomes. Due to advancements in the field of biomedical science, microalgae have significant potential for use in diabetic wound healing and other wound healing applications. This review delves into the physiological process of wound healing, the use of microalgae in wound healing, and a detailed explanation of the wound healing roles of various microalgal originated bioactive compounds including alginate, pigments, fatty acids, proteins, polysaccharides, flavonoids and phenols. The study discusses the efficacy of photosynthetic hydrogels in drugs and oxygen delivery to the wounded area that is crucial for promoting a good healing process, as well as highlights the drawbacks and challenges involved in using microalgae for wound healing. Given the current state of the art in utilizing microalgae for wound care, this review provides new perspectives for further research, along with insightful advice and innovative suggestions for academics engaged in this area.

Efficiently managing agricultural waste while innovating to derive value-added products is a significant challenge in the 21st century. In recent decades, these by-products have been increasingly explored as alternative sources for materials such as biosilica. Biosilica is renowned for its high surface area, biocompatibility, chemical stability, and modifiable surface, which makes it suitable for various applications. Additionally, the biomineralization process-biosilicification-in living organisms like diatoms offers an eco-friendly pathway for silica production. Despite the potential applications of biosilica, research on its use in sensor technology remains limited. This review aims to address this gap by covering the primary methodologies for extracting silica from biomass, discussing key techniques for its characterization, and highlighting its potential for functionalization in diverse applications. Special emphasis is given to the utility of diatom-derived biosilicas in developing sensors for detecting gaseous molecules and biomolecules.

Due to repeated microbial infection, persistent inflammation, excessive oxidative stress, and cell dysfunction, chronic wounds are difficult to heal, posing a serious threat to public health. Therefore, developing multifunctional wound dressings that can regulate the complex microenvironment of chronic wounds and enhance cellular function holds great significance. Recently, chitosan has emerged as a promising biopolymer for wound healing due to its excellent biocompatibility, biodegradability, and versatile bioactivity. The aim of this review is to provide a comprehensive understanding of the mechanisms of delayed chronic wound healing and discuss the healing-promoting properties of chitosan and its derivatives, such as good biocompatibility, antibacterial activity, hemostatic capacity, and the ability to promote tissue regeneration. On this basis, the potential applications of chitosan-based hydrogels are summarized in chronic wound healing, including providing a suitable microenvironment, eliminating bacterial infections, promoting hemostasis, inhibiting chronic inflammation, alleviating oxidative stress, and promoting tissue regeneration. In addition, the concerns and perspectives for the clinical application of chitosan-based hydrogels are also discussed.

Flexible conductive hydrogels hold great promise for applications in motion and medical detection. It is difficult to produce conductive hydrogel epidermal sensors in wearable hydrogels with dependable adhesion, sensing, and wound-healing properties. Nano-Fe3O4 was used as physical cross-linking points in the polyacrylamide/polyvinyl alcohol double network (PP) to increase the strain capacity of the hydrogel. The conductive lignin-dopamine (LD) was immobilized on the surface of Fe3O4 particles, and the LD-coated Fe3O4 was then incorporated into the double network hydrogel to create the PP/LD/Fe3O4 hydrogel. This work was done to look into the possibility of using Fe3O4 hydrogels as flexible strain sensors. The addition of LD/Fe3O4 caused the composite hydrogel to strain up to 124 %, with a modulus of elasticity of 21,308 Pa and electrical conductivity as high as 2.3 S•m-1 following the introduction of LD/Fe3O4. Moreover, the PP/LD/Fe3O4 hydrogel's adhesive qualities offered adequate antimicrobial properties and promoted wound healing. These results indicate that the developed electricity-responsive and tissue-adhesive hydrogel dressing offers a candidate to serve as a tissue sealant for wound healing.

Although various chemically synthesized materials are essential in medicine, food, and agriculture, they can exert unexpected side effects on the environment and human health by releasing certain toxic chemicals. Therefore, eco-friendly and biocompatible biomaterials based on natural resources are being actively explored. Recently, biosilica derived from diatoms has attracted attention in various biomedical fields, including drug delivery systems (DDS), due to its uniform porous nano-pattern, hierarchical structure, and abundant silanol functional groups. Importantly, the structural characteristics of diatom biosilica improve the solubility of poorly soluble substances and enable sustained release of loaded drugs. Additionally, diatom biosilica predominantly comprises SiO2, has high biocompatibility, and can easily hybridize with other DDS platforms, including hydrogels and cationic DDS, owing to its strong negative charge and abundant silanol groups. This review explores the potential applications of various diatom biosilica-based DDS in various biomedical fields, with a particular focus on hybrid DDS utilizing them.

The 3D nanopatterned silica shells of diatoms have gained attention as drug delivery vehicles because of their high porosity, extensive surface area, and compatibility with living organisms. Tooth extraction may result in various complications, including impaired blood clotting, desiccation of the root canal, and infection. Therapeutic sponges that possess multiple properties, such as the ability to stop bleeding and kill bacteria, provide numerous advantages for the healing of the area where a tooth has been removed. This study involved the fabrication of a composite material with antibacterial and hemostatic properties for dental extraction sponges. We achieved this by utilizing the porous nature and hemostatic capabilities of diatom biosilica. The antibiotic used was doxycycline. The gelatin-based diatom biosilica composite with antibiotics had the ability to prevent bleeding and release the antibiotic over a longer time compared to gelatin sponge. These properties indicate its potential as a highly promising medical device for facilitating rapid healing following tooth extraction.

Regenerative medicine aims to address substantial defects by amplifying the body's natural regenerative abilities and preserving the health of tissues and organs. To achieve these goals, materials that can provide the spatial and biological support for cell proliferation and differentiation, as well as the micro-environment essential for the intended tissue, are needed. Scaffolds such as polymers and metallic materials provide three-dimensional structures for cells to attach to and grow in defects. These materials have limitations in terms of mechanical properties or biocompatibility. In contrast, biominerals are formed by living organisms through biomineralization, which also includes minerals created by replicating this process. Incorporating biominerals into conventional materials allows for enhanced strength, durability, and biocompatibility. Specifically, biominerals can improve the bond between the implant and tissue by mimicking the micro-environment. This enhances cell differentiation and tissue regeneration. Furthermore, biomineral composites have wound healing and antimicrobial properties, which can aid in wound repair. Additionally, biominerals can be engineered as drug carriers, which can efficiently deliver drugs to their intended targets, minimizing side effects and increasing therapeutic efficacy. This article examines the role of biominerals and their composite materials in regenerative medicine applications and discusses their properties, synthesis methods, and potential uses.

Particles with a porous structure can lead to quick hemostasis and provide a good matrix for cell proliferation during wound healing. Recently, many particle-based wound healing materials have been clinically applied. However, these products show good hemostatic ability but with poor wound healing ability. To solve this problem, this study fabricated APGG composite particles using yeast β-glucan (obtained from Saccharomyces cerevisiae), sodium alginate, and γ-polyglutamic acid as the starting materials. The structure of yeast β-glucan was modified with many carboxymethyl groups to obtain carboxymethylated β-glucan, which could coordinate with Ca2+ ions to form a crosslinked structure. A morphology study indicated that the APGG particles showed an irregular spheroidal structure with a low density (<0.1 g cm-3) and high porosity (>40%). An in vitro study revealed that the particles exhibited a low BCI value, low hemolysis ratio, and good cytocompatibility against L929 cells. The APGG particles could quickly stop bleeding in a mouse liver injury model and exhibited better hemostatic ability than the commercially available product Celox. Furthermore, the APGG particles could accelerate the healing of non-infected wounds, and the expression levels of CD31, α-SMA, and VEGF related to angiogenesis were significantly enhanced.

Diabetic wound healing is delayed due to persistent inflammation, and macrophage-immunomodulating biomaterials can control the inflammatory phase and shorten the healing time. In this study, acellular embryoid bodies (aEBs) were prepared and mixed with thermosensitive hydroxybutyl chitosan (HBC) hydrogels to produce aEB/HBC composite hydrogels. The aEB/HBC composite hydrogels exhibited reversible temperature-sensitive phase transition behavior and a hybrid porous network. In vitro analysis showed that the aEB/HBC composite hydrogels exhibited better antimicrobial activity than the PBS control, aEBs or HBC hydrogels and promoted M0 to M2 polarization but not M1 to M2 macrophage repolarization in culture. The in vivo results showed that the aEB/HBC composite hydrogels accelerated cutaneous wound closure, re-epithelialization, ingrowth of new blood vessels, and collagen deposition and reduced the scar width during wound healing in diabetic mice over time. Macrophage phenotype analysis showed that the aEB/HBC composite hydrogels induce M2 macrophage reactions continually, upregulate M2-related mRNA and protein expression and downregulate M1-related mRNA and protein expression. Therefore, the aEB/HBC composite hydrogels have excellent antimicrobial activity, promote M2 macrophage polarization and accelerate the functional and structural healing of diabetic cutaneous wounds.

Diatom biosilica is an important natural source of porous silica, with three-dimensional ordered and nanopatterned structures referred to as frustules. The unique features of diatom frustules, such as their high specific surface area, thermal stability, biocompatibility, and adaptable surface chemistry, render diatoms valuable materials for high value-added applications. These attributes make diatoms an exceptional cost-effective raw material for industrial use. The functionalization of diatom biosilica surface improves its biophysical properties and increases the potential applications. This review focuses on the potential uses of diatom biosilica including traditional approaches and recent progress in biomedical applications. Not only well-studied drug delivery systems but also promising uses on bone regeneration and wound healing are covered. Furthermore, considerable aspects and possible future directions for the use of diatom biosilica materials are proposed to develop biomedical applications and merit further exploration.

A drug delivery system (DDS) is a useful technology that efficiently delivers a target drug to a patient's specific diseased tissue with minimal side effects. DDS is a convergence of several areas of study, comprising pharmacy, medicine, biotechnology, and chemistry fields. In the traditional pharmacological concept, developing drugs for disease treatment has been the primary research field of pharmacology. The significance of DDS in delivering drugs with optimal formulation to target areas to increase bioavailability and minimize side effects has been recently highlighted. In addition, since the burst release found in various DDS platforms can reduce drug delivery efficiency due to unpredictable drug loss, many recent DDS studies have focused on developing carriers with a sustained release. Among various drug carriers, mesoporous silica DDS (MS-DDS) is applied to various drug administration routes, based on its sustained releases, nanosized porous structures, and excellent solubility for poorly soluble drugs. However, the synthesized MS-DDS has caused complications such as toxicity in the body, long-term accumulation, and poor excretion ability owing to acid treatment-centered manufacturing methods. Therefore, biosilica obtained from diatoms, as a natural MS-DDS, has recently emerged as an alternative to synthesized MS-DDS. This natural silica carrier is an optimal DDS platform because culturing diatoms is easy, and the silica can be separated from diatoms using a simple treatment. In this review, we discuss the manufacturing methods and applications to various disease models based on the advantages of biosilica.

Antibacterial and hemostatic properties are essential for wound healing dressing. In this study, a new type of hydrogel composed of gelatin methacryloyl (GelMA) and hyaluronic acid-aldehyde (HA-CHO) is fabricated by photo-crosslinking and respectively loaded with a single drug gentamicin sulfate (GS), and two drugs of GS and lysozyme (LZM). The composite hydrogel of GelMA and HA-CHO is successfully synthesized by the aldehyde and Schiff base reactions. The structures and compositions of the hydrogels with and without drug loaded are characterized by FT-IR, ¹H NMR, and XPS. Furthermore, the microstructure and swelling behaviour of hydrogels prove that the content of HA-CHO has a significant role in the formation of hydrogels with dense porous structures and super absorbent. pH 7.4 and pH 5.0 conditions are used to evaluate the drug release behaviour of the obtained hydrogels. The released amount of GS of the drug-loaded hydrogels in the acidic buffer is more than that of the physiological environment because of the cleaved Schiff base bonds and the electrostatic interaction. Especially for the dual drug-loaded hydrogel GelMA/HA-CHO/GS/LZM, the released ratio of GS is elevated from 59 % in pH 7.4 buffer to about 78 % in pH 5.0 buffer within the first 6 h, which verifies the excellent pH-stimulus responsiveness. These endow the GS-LZM dual drug-loaded hydrogels with superior antibacterial efficiencies to that of the single GS drug-loaded hydrogels, no drug-loaded hydrogels, and SEBS control, especially in inhibiting S. aureus in a lower concentration of 10⁶ CFU mL^-1, which can be attributed to the synergistic effect of LZM and GS. For S. aureus at 10⁶ CFU mL^-1, the bacterial survival of GelMA/HA-CHO/GS/LZM is 1.1 %, which shows outstanding antibacterial effect. Hence, the drug-loaded hydrogels, especially the dual drug-loaded hydrogels with pH-responsive, antibacterial, and hemostatic properties have great potential as wound healing materials.

Bletilla striata polysaccharide (BSP) is effective for wound healing and has important applications in health care. A series of blend hydrogels was designed with BSP and konjac glucomannan (KGM) in this study to overcome the deficient mechanical performance caused by the excessive dissolution of BSP without affecting its physiological activity. The interplay between them, as well as the effects of KGM concentration on the physical properties and microstructures of hydrogels, were also explored. It was proved that the frame of the hydrogel was primarily formed by KGM. BSP was dispersed uniformly and linked to KGM through hydrogen bonding, which effectively improved the physical properties, such as increasing the water-holding capacity, improving the swelling degree, and enhancing the mechanical properties. Blend hydrogel BK2-2 (containing 1.0% BSP and 1.0% KGM, w/v) was found to be the optimal formulation based on the thermal stability and microstructure, which was used for further research. In vitro experiments revealed the L929 cell proliferative effects of the blend hydrogel, and no difference was found with BSP sponge extract after 72 h of exposure. In vivo animal studies indicated that the BK2-2 accelerated wound healing compared with the control group; however, no difference was found with dressings only made of BSP. These results demonstrated that KGM improved the physical properties of BSP-based material without negatively affecting its physiological properties. Also, the BSP/KGM blend hydrogel had good comprehensive properties and is expected to be used as a wound healing material in the future.

Ocean resources are a priceless repository of unique species and bioactive compounds with denouement properties that can be used in the fabrication of advanced biomaterials as new templates for supporting the cell culture envisaging tissue engineering approaches. The collagen of marine origin can be sustainably isolated from the underrated fish processing industry by-products, while silica and related materials can be found in the spicules of marine sponges and diatoms frustules. Aiming to address the potential of biomaterials composed from marine collagen and silica-based materials in the context of bone regeneration, four different 3D porous structure formulations (COL, COL:BG, COL:D.E, and COL:BS) were fabricated by freeze-drying. The skins of Atlantic cod (Gadus morhua) were used as raw materials for the collagen (COL) isolation, which was successfully characterized by SDS-PAGE, FTIR, CD, and amino acid analyses, and identified as a type I collagen, produced with a 1.5% yield and a preserved characteristic triple helix conformation. Bioactive glass 45S5 bioglass® (BG), diatomaceous earth (D.E.) powder, and biosilica (BS) isolated from the Axinella infundibuliformis sponge were chosen as silica-based materials, which were obtained as microparticles and characterized by distinct morphological features. The biomaterials revealed microporous structures, showing a porosity higher than 85%, a mean pore size range of 138-315 μm depending on their composition, with 70% interconnectivity which can be favorable for cell migration and ensure the needed nutrient supply. In vitro, biological assays were conducted by culturing L929 fibroblast-like cells, which confirmed not only the non-toxic nature of the developed biomaterials but also their capability to support cell adhesion and proliferation, particularly the COL:BS biomaterials, as observed by calcein-AM staining upon seven days of culture. Moreover, phalloidin and DAPI staining revealed well-spread cells, populating the entire construct. This study established marine collagen/silica biocomposites as potential scaffolds for tissue engineering, setting the basis for future studies, particularly envisaging the regeneration of non-load-bearing bone tissues.