From shield to spear: Charge-reversible nanocarriers in overcoming cancer therapy barriers

• Madhuri Yeduvaka,
• Pooja Mittal,
• Ameer Boyalakuntla,
• Usman Bee Shaik,
• Himanshu Sharma,
• Thakur Gurjeet Singh,
• Siva Nageswara Rao Gajula and
• Lakshmi Vineela Nalla

Beilstein J. Nanotechnol. 2026, 17, 159–175, doi:10.3762/bjnano.17.10

• biodistribution while protecting fragile biomolecules such as proteins and nucleic acids [11]. Through targeted and sustained release, these systems enhance therapeutic efficacy, prolong circulation, and reduce systemic toxicity compared to conventional formulations [12][13]. As illustrated in Figure 1

• physicochemical parameters, the surface charge is essential for determining nanocarrier interactions with biological membranes, cellular uptake, and biodistribution [17]. With a positive charge, the nanocarrier tends to be absorbed by high plasma proteins and cleared faster from the bloodstream. In contrast

• et al. developed a dual immune checkpoint-inhibiting nanocarrier, aLS@VpNPs, which is cloaked with triple-negative breast cancer (TNBC) cell membranes and incorporates anti-LAG3 and Siglec10 proteins. This biomimetic design enhances tumour targeting and biocompatibility. Moreover, the nanocarrier is

Influence of surface characteristics on the in vitro stability and cell uptake of nanoliposomes for brain delivery

• Dushko Shalabalija,
• Ljubica Mihailova,
• Nikola Geskovski,
• Andreas Zimmer,
• Otmar Geiss,
• Sabrina Gioria,
• Diletta Scaccabarozzi and
• Marija Glavas Dodov

Beilstein J. Nanotechnol. 2026, 17, 139–158, doi:10.3762/bjnano.17.9

• NLs interact with biomolecules, thus forming a protein corona (PC), altering functional proteins, and engaging in redox reactions with reactive species [6]. These interactions can affect the functionality, biodistribution, targeting, and cell internalization of NLs. Serum components can disrupt the

• lipid structure of NLs, leading to AC leakage, while plasma protein adsorption may cause particle aggregation [7]. In this sense, the presence of proteins in the tissue environment can alter cellular uptake of both cationic and anionic carriers [8]. In short, our understanding of how nanodelivery

• set to 1.38 and 0.010, respectively. Water was set as the dispersant, the temperature was set to 25 °C, while the attenuation was set to 11. The 'general purpose (normal distribution)' was chosen as the analysis model. High-resolution automated electrophoresis of the adsorbed proteins onto

Development and in vitro evaluation of liposomes and immunoliposomes containing 5-fluorouracil and R-phycoerythrin as a potential phototheranostic system for colorectal cancer

• Raissa Rodrigues Camelo,
• Vivianne Cortez Sombra Vandesmet,
• Octavio Vital Baccallini,
• José de Brito Vieira Neto,
• Thais da Silva Moreira,
• Luzia Kalyne Almeida Moreira Leal,
• Claudia Pessoa,
• Daniel Giuliano Cerri,
• Maria Vitória Lopes Badra Bentley,
• Josimar O. Eloy,
• Ivanildo José da Silva Júnior and
• Raquel Petrilli

Beilstein J. Nanotechnol. 2026, 17, 97–121, doi:10.3762/bjnano.17.7

• lipophilic substances. Furthermore, liposomes can also act as a protein delivery system, reducing enzymatic degradation of proteins and enhancing their stability and their permeability through cell membranes [7]. Immunoliposomes provide many advantages by surface functionalization with targeting biomolecules

• extracted R-PE (0.73) suggests the presence of other biomolecules – such as polysaccharides and residual proteins – which may further contribute to membrane stabilization during liposome formation [15]. For 5-FU, no significant difference was observed between the HSPC 25 and HSPC 50 formulations, which may

• structural and functional integrity of the bioactive compounds. 3.5 Stability of nanoparticles in serum Assessing colloidal stability in bovine serum is a critical parameter for inferring the in vivo behavior of nanostructured systems, as the presence of plasma proteins can induce adsorption on the particle

Chiral plasmonic nanostructures fabricated with circularly polarized light

• Tian Qiao and
• Ming Lee Tang

Beilstein J. Nanotechnol. 2025, 16, 2245–2264, doi:10.3762/bjnano.16.154

• two proteins due to the supramolecular interactions between the chiral extracellular domains and the curved chiral nanoparticles, which led to the enantiomer-dependent immunological response. Nam et al. have shown that the stronger binding affinities of molecules to regions of both positive and

Optical bio/chemical sensors for vitamin B₁₂ analysis in food and pharmaceuticals: state of the art, challenges, and future outlooks

• Seyed Mohammad Taghi Gharibzahedi and
• Zeynep Altintas

Beilstein J. Nanotechnol. 2025, 16, 2207–2244, doi:10.3762/bjnano.16.153

• when the capacity of the IF system is exceeded [50]. In the active transport pathway, the absorption of VB12 through receptors commences following its liberation from the dietary source. Food proteins act as carriers for dietary VB12. The acidic conditions within the gastric lumen enable the liberation

• forms (AdoCbl and MeCbl), via a complicated intracellular process involving various chaperone proteins and transporters, regardless of its form when ingested [34][47][50][55]. Acting as the main chaperone, the methylmalonic aciduria and homocystinuria type-C protein (MMACHC) captures VB12 exiting the

• -methyltetrahydrofolate (5-MTHF) donates the methyl group and is thereafter transformed into tetrahydrofolate. Methionine is then converted into S-adenosylmethionine (SAM), which serves as a vital methyl donor for the methylation of proteins, phospholipids, neurotransmitters, RNA, and DNA. In contrast, Ado-Cbl acts as a

Ultrathin water layers on mannosylated gold nanoparticles

• Maiara A. Iriarte Alonso,
• Jorge H. Melillo,
• Silvina Cerveny,
• Yujin Tong and
• Alexander M. Bittner

Beilstein J. Nanotechnol. 2025, 16, 2183–2198, doi:10.3762/bjnano.16.151

• nanoparticle systems, one functionalized with an oligo(ethylene glycol) ligand, and one functionalized with a mixture of the same with a dimannoside ligand. The dimannoside ligand was chosen to mimic the surface chemistry of viral spike proteins. We characterized the particles by electron microscopy, dynamic

• properties on particle size and shape has been demonstrated for particle sizes in the 1–100 nm range and on biological interfaces [7]. Limited biocompatibility and high tendency to aggregate in solution inspired new mechanisms of particle biofunctionalization with proteins, lipids, or carbohydrates. Coupling

• or humid environments are not well known, although there are many examples, for example, sensors that use antibodies (glycosylated proteins) linked to AuNPs, such as the now very established SARS-CoV-2 antigen tests [5]. While practical questions about storage conditions and lifetimes call for tests

Rapid synthesis of highly monodisperse AgSbS₂ nanocrystals: unveiling multifaceted activities in cancer therapy, antibacterial strategies, and antioxidant defense

• Funda Ulusu,
• Adem Sarilmaz,
• Yakup Ulusu,
• Faruk Ozel and
• Mahmut Kus

Beilstein J. Nanotechnol. 2025, 16, 2105–2115, doi:10.3762/bjnano.16.145

• nanoparticles with bacterial cells and the production of ROS, which causes DNA damage and denaturation of proteins close to the bacterial membrane, causes cell membrane damage [37][38]. In addition, the electrostatic force generated between the bacterial cells and the synthesized NCs causes distraction of the

Molecular and mechanical insights into gecko seta adhesion: multiscale simulations combining molecular dynamics and the finite element method

• Yash Jain,
• Saeed Norouzi,
• Tobias Materzok,
• Stanislav N. Gorb and
• Florian Müller-Plathe

Beilstein J. Nanotechnol. 2025, 16, 2055–2076, doi:10.3762/bjnano.16.141

• . Spatulae and substrate: particles Mesoscale spatula model The mesoscale spatula model was derived from prior research. Its shape is based on SEM images [23], and the force field was derived bottom-up from united-atom gecko keratin simulations [12]. The keratin proteins in gecko seta and spatulae form a

The cement of the tube-dwelling polychaete Sabellaria alveolata: a complex composite adhesive material

• Emilie Duthoo,
• Aurélie Lambert,
• Pierre Becker,
• Carla Pugliese,
• Jean-Marc Baele,
• Arnaud Delfairière,
• Matthew J. Harrington and
• Patrick Flammang

Beilstein J. Nanotechnol. 2025, 16, 1998–2014, doi:10.3762/bjnano.16.138

• several studies. However, some aspects of cement formation are still poorly understood and several differences have been pointed out between the two main model species. This study aims to investigate the adhesive system of Sabellaria alveolata by identifying new potential adhesive proteins, as well as

• describing the ultrastructure and elemental composition of the cement cells and their secretion. Different adhesive proteins are packaged in one or the other of two types of cement cells, namely, those containing homogeneous granules and those containing heterogeneous granules with lamellar inclusions

• . Phosphoserine has been identified as one of the main modified amino acids in tubeworm cement and, using in situ hybridization, we propose that FAM20C kinases would be the enzymes responsible for the phosphorylation of serine residues in adhesive proteins. Comparison between the ultrastructure of the granules

PEGylated lipids in lipid nanoparticle delivery dynamics and therapeutic innovation

• Peiyang Gao

Beilstein J. Nanotechnol. 2025, 16, 1914–1930, doi:10.3762/bjnano.16.133

• physicochemical properties would be PEG-specific and not translatable between studies. LNP pegylation-associated trade-off between nonspecific binding and cellular interactions When LNPs are introduced into biological systems, they encounter a complex milieu of biomolecules, predominantly proteins, which can

• ]. PEG’s hydrophilic and steric properties are instrumental in reducing the adsorption of proteins onto LNP surfaces. By creating a hydrated barrier, PEG minimizes nonspecific binding, leading to a “stealth” effect that prolongs circulation time and reduces recognition by the mononuclear phagocytic system

• [24]. However, the effectiveness of this barrier depends on PEG density, molecular weight, and chain configuration. The previously mentioned high-density PEG layers in a “brush” conformation are particularly effective at repelling proteins compared to lower-density “mushroom” configurations, which may

Self-assembly and adhesive properties of Pollicipes pollicipes barnacle cement protein cp19k: influence of pH and ionic strength

• Shrutika Sawant,
• Anne Marie Power and
• J. Gerard Wall

Beilstein J. Nanotechnol. 2025, 16, 1863–1872, doi:10.3762/bjnano.16.129

• Sciences, University of Galway H91 TK33, Ireland 10.3762/bjnano.16.129 Abstract Marine organisms such as barnacles rely on a complex underwater adhesive system, driven by self-assembly and intermolecular associations between cement proteins, for permanent attachment to a variety of surface types. In this

• may help to inform the design of eco-friendly adhesives for application in biomedicine, industry, and underwater engineering [2][3]. Mussel adhesive proteins are the most extensively studied of marine bioadhesives. Mussels anchor to submerged surfaces using a byssus, a bundle of proteinaceous threads

• secreted by the foot [4]. Each thread ends in an adhesive plaque composed of mussel foot proteins (Mfps), which are rich in the modified amino acid ʟ-3,4-dihydroxyphenylalanine (DOPA) [5]. DOPA is formed via post-translational hydroxylation of tyrosine and mediates wet surface adhesion through hydrogen

On the road to sustainability – application of metallic nanoparticles obtained by green synthesis in dentistry: a scoping review

• Lorena Pinheiro Vasconcelos Silva,
• Joice Catiane Soares Martins,
• Israel Luís Carvalho Diniz,
• Júlio Abreu Miranda,
• Danilo Rodrigues de Souza,
• Éverton do Nascimento Alencar,
• Moan Jéfter Fernandes Costa and
• Pedro Henrique Sette-de-Souza

Beilstein J. Nanotechnol. 2025, 16, 1851–1862, doi:10.3762/bjnano.16.128

• extracts, several compounds, such as phenols, flavonoids, terpenoids, alkaloids, and proteins, play crucial roles in reducing metal ions and stabilizing nanoparticles, thereby eliminating the need for harsh chemical catalysts [12][13][14]. This technique is widely regarded as a clean technology as it

Exploring the potential of polymers: advancements in oral nanocarrier technology

• Rousilândia de Araujo Silva,
• Igor Eduardo Silva Arruda,
• Luise Lopes Chaves,
• Mônica Felts de La Roca Soares and
• Jose Lamartine Soares Sobrinho

Beilstein J. Nanotechnol. 2025, 16, 1751–1793, doi:10.3762/bjnano.16.122

• walls. Since mucus is continuously secreted along the GIT, it is subsequently eliminated due to the cellular renewal process [5]. Mucus is a complex hydrogel comprising proteins, carbohydrates, lipids, salts, antibodies, bacteria, and cellular debris. Mucins are the primary protein component of mucus

• protrusions induced by growth factors, bacteria, viruses, and necrotic cells. These protrusions either collapse into endocytic vesicles or retract into the membrane, fusing with it and forming macropinosomes [80]. CME involves interactions between clathrin-associated adaptors and sorting proteins, forming

• polymers Nanotechnological systems derived from natural polymers found in biological species, such as proteins and polysaccharides, are referred to as biopolymeric NPs. Examples of natural polymers utilized in these NPs include casein, zein, hyaluronic acid, alginate, and chitosan [89]. Biopolymers are

Advances of aptamers in esophageal cancer diagnosis, treatment and drug delivery

• Yang Fei,
• Hui Xu,
• Chunwei Zhang,
• Jingjing Wang and
• Yong Jin

Beilstein J. Nanotechnol. 2025, 16, 1734–1750, doi:10.3762/bjnano.16.121

• . These sensors feature minimal invasiveness and low detection limits, demonstrating unique advantages in the early detection of cancer biomarker proteins. Moreover, an advanced drug delivery platform [28] was engineered by functionalizing nanocarriers with the AS1411 aptamer, enabling the targeted co

• , peptide aptamers exhibit target specificity predominantly limited to protein molecules, representing a relatively constrained target spectrum. Nucleic acid aptamers, which can bind to proteins, genes, small molecules, cells and other targets, are commonly used in laboratory and clinical practice and

• disease progression, primarily encompassing proteins, nucleic acids, metabolites, and cellular components [44]. To be clinically relevant, these markers must demonstrate both high sensitivity and specificity, enabling robust diagnostic and prognostic capabilities. Most biosensors for cancer detection use

Multifunctional anionic nanoemulsion with linseed oil and lecithin: a preliminary approach for dry eye disease

• Niédja Fittipaldi Vasconcelos,
• Almerinda Agrelli,
• Rayane Cristine Santos da Silva,
• Carina Lucena Mendes-Marques,
• Isabel Renata de Souza Arruda,
• Priscilla Stela Santana de Oliveira,
• Mércia Liane de Oliveira and
• Giovanna Machado

Beilstein J. Nanotechnol. 2025, 16, 1711–1733, doi:10.3762/bjnano.16.120

Prospects of nanotechnology and natural products for cancer and immunotherapy

• Jan Filipe Andrade Santos,
• Marcela Bernardes Brasileiro,
• Pamela Danielle Cavalcante Barreto,
• Ligiane Aranha Rocha and
• José Adão Carvalho Nascimento Júnior

Beilstein J. Nanotechnol. 2025, 16, 1644–1667, doi:10.3762/bjnano.16.116

• vasculature of these cells compared to healthy ones. Upon absorption of light during photodynamic therapy, Ce6 generates ROS, causing damage to the cell membrane, proteins, and DNA of the cancer cells, ultimately leading to their destruction. Additionally, the ROS produced by Ce6 destroys the vascular layer

• glycolysis, reducing angiogenesis, and promoting the degradation of oncogenic proteins [162][163]. The invention proposes the use of carbon dots (CDs) loaded with BER as an API, with a sustained drug release that increases upon contact with the acidic conditions surrounding tumors. Both non-loaded CDs and

Venom-loaded cationic-functionalized poly(lactic acid) nanoparticles for serum production against Tityus serrulatus scorpion

• Philippe de Castro Mesquita,
• Karla Samara Rocha Soares,
• Manoela Torres-Rêgo,
• Emanuell dos Santos-Silva,
• Mariana Farias Alves-Silva,
• Alianda Maira Cornélio,
• Matheus de Freitas Fernandes-Pedrosa and
• Arnóbio Antônio da Silva-Júnior

Beilstein J. Nanotechnol. 2025, 16, 1633–1643, doi:10.3762/bjnano.16.115

• polyethylenimine for loading peptides and proteins of T. serrulatus venom, and their use as a potential immunoadjuvant was evaluated. The protein loading efficiency of about 100% and the polyacrylamide gel electrophoresis assay confirmed the success of venom loading. Dynamic light scattering and zeta potential

• analysis supported small and narrow-sized cationic functionalized nanoparticles. Atomic force microscopy and scanning electron microscopy images showed nanoparticles with a spherical and smooth shape. The stability of tested formulations was accessed for six weeks, and the sustained release of proteins

• for advancing the studies in this field [8]. Tityus serrulatus venom is comprised of several compounds such as mucus, salts, proteins with high molecular mass, nucleotides, lipids, amino acids, hyaluronidase, hypotension factors, metalloproteases, and neurotoxins [7][9]. However, neurotoxins are

Cross-reactivities in conjugation reactions involving iron oxide nanoparticles

• Shoronia N. Cross,
• Katalin V. Korpany,
• Hanine Zakaria and
• Amy Szuchmacher Blum

Beilstein J. Nanotechnol. 2025, 16, 1504–1521, doi:10.3762/bjnano.16.106

• IONPs, using either amine- or carboxylic acid-functionalized IONPs, especially when biomolecules, such as proteins or peptides, are involved [3][7][8][9][10][11][12][13][14]. Sharpless et al. [6] have generally defined “click chemistry” as chemical processes that are highly selective, have a high

Enhancing the therapeutical potential of metalloantibiotics using nano-based delivery systems

• Alejandro Llamedo,
• Marina Cano,
• Raquel G. Soengas and
• Francisco J. García-Alonso

Beilstein J. Nanotechnol. 2025, 16, 1350–1366, doi:10.3762/bjnano.16.98

• , making them ideal for targeted drug delivery applications [87]. Mesoporous silica nanoparticles (MSiNPs) are a subclass of SiNPs known for their ordered pore structure, which allows for the encapsulation of large molecules and proteins. Due to their high surface area for drug loading and also to the fact

• antimicrobial agents since they usually exhibit superior antimicrobial activity compared to silver(I) alone [100]. The mechanism of action of most silver complexes is based on a slow release of the silver(I) ions, which react with the thiol groups of proteins or with key functional groups of enzymes; the

• coordinated ligands merely serve as carrier for silver(I) ions. Additionally, silver ions can also generate ROS, which target primarily lipids, DNA, RNA and proteins, leading to serious consequences [18]. Despite a complete understanding of the mechanisms of antibacterial action is yet to be achieved, it has

Ferroptosis induction by engineered liposomes for enhanced tumor therapy

• Alireza Ghasempour,
• Mohammad Amin Tokallou,
• Mohammad Reza Naderi Allaf,
• Mohsen Moradi,
• Hamideh Dehghan,
• Mahsa Sedighi,
• Mohammad-Ali Shahbazi and
• Fahimeh Lavi Arab

Beilstein J. Nanotechnol. 2025, 16, 1325–1349, doi:10.3762/bjnano.16.97

• structural and functional changes in proteins and nucleotide acids lead to toxic effects in the cell and initiate the ferroptosis cascade [37][38]. Due to the instability of lipid peroxides, it is not easy to detect them. Nevertheless, the secondary products of lipid peroxidation, such as malondialdehyde

• peroxides and the formation of non-toxic lipid alcohol under normal conditions [44]. Changes in GPX4 activity may indicate ferroptosis, which can be monitored by measuring NADPH and phosphatidylcholine hydroperoxide [45][46]. Heat shock proteins can also inhibit ferroptosis by stimulating GPX4 or regulating

• labile iron in a non-toxic and inorganic state [56]. Iron storage proteins play a unique role in the inhibition of ferroptosis. Inhibition of ferritinophagy by suppressing nuclear receptor coactivator 4 (NCOA4) and preventing ferritin degradation by lysosomes limits the incidence of ferroptosis [57]. In

Better together: biomimetic nanomedicines for high performance tumor therapy

• Imran Shair Mohammad,
• Gizem Kursunluoglu,
• Anup Kumar Patel,
• Hafiz Muhammad Ishaq,
• Cansu Umran Tunc,
• Dilek Kanarya,
• Mubashar Rehman,
• Omer Aydin and
• Yin Lifang

Beilstein J. Nanotechnol. 2025, 16, 1246–1276, doi:10.3762/bjnano.16.92

• physicochemical and biological properties, and incredible potential of being therapeutic agent carriers for biomedical applications [10][11]. They are capable to deliver a range of therapeutics including genes, vaccines, biological macromolecules, hydrophobic/hydrophilic drugs, and proteins to certain organs such

• electroporation (Figure 3C). Although electroporation is an easy and feasible loading method, its scale-up is challenging [29]. Many researchers have attached drugs, therapeutic proteins, or drug-loaded nanoparticles onto the surface of RBCs to transfer innate characteristics of RBCs to the nanoparticles (Figure

• recruiting other immune cells and also prevent the immune response from overreacting [38]. Therefore, T cells are the most extensively studied immune cells in cancer immunotherapy [39]. Kang et al. have developed T lymphocyte membrane-coated nanoparticles that can target cancer by T cell-associated proteins

Hydrogels and nanogels: effectiveness in dermal applications

• Jéssica da Cruz Ludwig,
• Diana Fortkamp Grigoletto,
• Daniele Fernanda Renzi,
• Wolf-Rainer Abraham,
• Daniel de Paula and
• Najeh Maissar Khalil

Beilstein J. Nanotechnol. 2025, 16, 1216–1233, doi:10.3762/bjnano.16.90

• , such as primary amines and sulfhydryl groups on proteins or other biomolecules. The reactive chemical group is the most important property of a cross-linker. The reactive group establishes the method and mechanism for polymer modification [43][45]. Harsh conditions such as low pH and high temperature

• nucleic acids and proteins [48][132]. Different techniques have been tested for the preparation of chitosan hydrogels, including ionotropic gelation [76], emulsion polymerization [108], and copolymerization [57][133]. Chitosan can be cross-linked with several organic and inorganic compounds due to its

• as drug carriers to deliver hydrophobic [153] and hydrophilic [154] molecules as well as biomolecules, including proteins [155] and nucleic acids [156]. These nanocarriers can be obtained from biodegradable and biocompatible materials [157], showing singular properties, such as stimuli-responsiveness

Investigation of the solubility of protoporphyrin IX in aqueous and hydroalcoholic solvent systems

• Michelly de Sá Matsuoka,
• Giovanna Carla Cadini Ruiz,
• Marcos Luciano Bruschi and
• Jéssica Bassi da Silva

Beilstein J. Nanotechnol. 2025, 16, 1209–1215, doi:10.3762/bjnano.16.89

• , at a specific wavelength, PpIX absorbs energy and transfers it to molecular oxygen, generating reactive oxygen species (ROS). These ROS are highly toxic to cells, inducing oxidative damage in various biomolecules such as lipids, proteins and DNA, leading to cell death [6][7]. However, PpIX and other

Mechanical stability of individual bacterial cells under different osmotic pressure conditions: a nanoindentation study of Pseudomonas aeruginosa

• Lizeth García-Torres,
• Idania De Alba Montero,
• Eleazar Samuel Kolosovas-Machuca,
• Facundo Ruiz,
• Sumati Bhatia,
• Jose Luis Cuellar Camacho and
• Jaime Ruiz-García

Beilstein J. Nanotechnol. 2025, 16, 1171–1183, doi:10.3762/bjnano.16.86

• patients [6][7][8]. As a Gram-negative bacterium, PA is characterized by a distinctive cell wall structure constituted by a thin peptidoglycan layer enclosed by an outer membrane which contains lipopolysaccharides (LPS) [9][10][11]. The outer membrane also contains numerous proteins, lipoproteins, and

• channels contributing to its selective permeability [12][13]. Also integrated into the outer membrane, specific tension-activated channel proteins are responsible for the osmoregulation of the membrane envelope and its protection from threatening conditions such as severe osmotic downshocks, which can lead

• to an excessive increase in the membrane tension resulting in rupture [14][15]. The mechanosensitive (MS) family of channel proteins have been identified as the main efflux pumps required by PA to regulate the exit of osmolytes and reduce the membrane tension to acceptable life-compatible values

Piezoelectricity of hexagonal boron nitrides improves bone tissue generation as tested on osteoblasts

• Sevin Adiguzel,
• Nilay Cicek,
• Zehra Cobandede,
• Feray B. Misirlioglu,
• Hulya Yilmaz and
• Mustafa Culha

Beilstein J. Nanotechnol. 2025, 16, 1068–1081, doi:10.3762/bjnano.16.78

• nucleation of calcium and phosphate ions, imparting stiffness and resistance to bone. Additionally, collagen and noncollagenous matrix proteins contribute to bone formation by offering a scaffold for hydroxyapatite deposition [2][3]. Bone tissue consists of four main cell types: bone lining cells

• ]. Osteocytes, the longest-lived bone cells, arise from osteoblast differentiation and regulate bone maintenance [7]. Osteoblasts, found on bone surfaces, drive bone formation through two key steps: matrix deposition and mineralization. During matrix deposition, collagen and noncollagenous proteins are secreted

• , activation of the calcium/calmodulin pathway leads to the expression of transforming growth factor-β (TGF-β), bone morphogenetic proteins (BMPs), and other regulatory factors which control extracellular matrix production, bone homeostasis, tissue repair, and mesenchymal stem cell (MSC) differentiation [10