Natural Biomolecules Research Articles

Lipid-based nanoparticles as drug delivery carriers for cancer therapy.

Cancer is a severe disease that results in death in all countries of the world. A nano-based drug delivery approach is the best alternative, directly targeting cancer tumor cells with improved drug cellular uptake. Different types of nanoparticle-based drug carriers are advanced for the treatment of cancer, and to increase the therapeutic effectiveness and safety of cancer therapy, many substances have been looked into as drug carriers. Lipid-based nanoparticles (LBNPs) have significantly attracted interest recently. These natural biomolecules that alternate to other polymers are frequently recycled in medicine due to their amphipathic properties. Lipid nanoparticles typically provide a variety of benefits, including biocompatibility and biodegradability. This review covers different classes of LBNPs, including their characterization and different synthesis technologies. This review discusses the most significant advancements in lipid nanoparticle technology and their use in medicine administration. Moreover, the review also emphasized the applications of lipid nanoparticles that are used in different cancer treatment types.

Bacterioruberin: Biosynthesis, Antioxidant Activity, and Therapeutic Applications in Cancer and Immune Pathologies.

Halophilic archaea, also termed haloarchaea, are a group of moderate and extreme halophilic microorganisms that constitute the major microbial populations in hypersaline environments. In these ecosystems, mainly aquatic, haloarchaea are constantly exposed to ionic and oxidative stress due to saturated salt concentrations and high incidences of UV radiation (mainly in summer). To survive under these harsh conditions, haloarchaea have developed molecular adaptations including hyperpigmentation. Regarding pigmentation, haloarchaeal species mainly synthesise the rare C50 carotenoid called bacterioruberin (BR) and its derivatives, monoanhydrobacterioruberin and bisanhydrobacterioruberin. Due to their colours and extraordinary antioxidant properties, BR and its derivatives have been the aim of research in several research groups all over the world during the last decade. This review aims to summarise the most relevant characteristics of BR and its derivatives as well as describe their reported antitumoral, immunomodulatory, and antioxidant biological activities. Based on their biological activities, these carotenoids can be considered promising natural biomolecules that could be used as tools to design new strategies and/or pharmaceutical formulas to fight against cancer, promote immunomodulation, or preserve skin health, among other potential uses.

First Report of Ocellatin-VT from the Skin Secretion of Leptodactylus vastus Lutz (Amphibia: Leptodactylidae)

The global emergency of antimicrobial resistance has drawn several efforts to evaluate new drug candidates, such as natural defensive biomolecules. Ocellatins are a group of antimicrobial peptides found in anurans of the Leptodactylidae family. This work investigated the presence of antimicrobial peptides in the skin secretion of Leptodactylus vastus from the Brazilian northeast. The secretion was fractionated by RP-HPLC, and the fractions were screened for antibacterial activity. A peptide isolated from the most active fraction was characterized for primary structure and evaluated for antibacterial activity, cytotoxicity to murine melanoma cells (B16-F10), and hemolytic activity. The RP-HPLC profile displayed 26 fractions, with fraction 25 being the most active. One of the two peptides present in this fraction had the primary structure determined, belonging to the group of ocellatins. Since it was not identical to other ocellatins previously reported, it was named ocellatin-VT. This peptide especially inhibited Gram-negative bacteria growth, with the highest activity against Acinetobacter baumannii and Escherichia coli (growth inhibition was higher than 95% at 8 and 16 µM, respectively). Ocellatin-VT was weakly cytotoxic to B16-F10 cells and showed low hemolytic activity. In conclusion, a new ocellatin was isolated from L. vastus skin secretion that was active against non-resistant and multidrug-resistant bacteria.

A multifunctional guanosine-based carbon dots for dead microbial imaging and synergistic broad-spectrum antimicrobial therapy

Pathogenic microbial infection poses serious threats to human lives and antibiotic abuse leads to bacterial resistance. The development of alternative antibacterial agents and strategies with reduced resistance risk is urgently demanded. Heteroatom doping is a feasible method for adjusting the electronic and optical properties of carbon dots (CDs) to improve their bioimaging performance and light-mediated therapeutic efficiency. Herein, we synthesized a series of guanosine-derived CDs from guanosine (G), guanosine monophosphate (GMP), guanosine diphosphate (GDP), and guanosine triphosphate (GTP) as respective precursors. G-CDs, prepared by guanosine with strong surface negative charge and suitable size, can successfully differentiate and stain dead microbial cells (bacteria and fungi). G-CDs with a high N content exhibited the highest antibacterial activity in vitro and in vivo among the four guanosine-derived CDs, owing to triple synergistic antibacterial actions - the intrinsic antibacterial mechanism, bacterial photodynamic and photothermal inactivation against bacteria and fungi. In this paper, we present a promising new method to prepare CDs using natural biomolecules from living systems as precursors for multifunctional dead microbial cells imaging and broad-spectrum theranostic applications.

The 3D-McMap Guidelines: Three-Dimensional Multicomposite Microsphere Adaptive Printing.

Microspheres, synthesized from diverse natural or synthetic polymers, are readily utilized in biomedical tissue engineering to improve the healing of various tissues. Their ability to encapsulate growth factors, therapeutics, and natural biomolecules, which can aid tissue regeneration, makes microspheres invaluable for future clinical therapies. While microsphere-supplemented scaffolds have been investigated, a pure microsphere scaffold with an optimized architecture has been challenging to create via 3D printing methods due to issues that prevent consistent deposition of microsphere-based materials and their ability to maintain the shape of the 3D-printed structure. Utilizing the extrusion printing process, we established a methodology that not only allows the creation of large microsphere scaffolds but also multicomposite matrices into which cells, growth factors, and therapeutics encapsulated in microspheres can be directly deposited during the printing process. Our 3D-McMap method provides some critical guidelines for issues with scaffold shape fidelity during and after printing. Carefully timed breaks, minuscule drying steps, and adjustments to extrusion parameters generated an evenly layered large microsphere scaffold that retained its internal architecture. Such scaffolds are superior to other microsphere-containing scaffolds, as they can release biomolecules in a highly controlled spatiotemporal manner. This capability permits us to study cell responses to the delivered signals to develop scaffolds that precisely modulate new tissue formation.

Novel Apoplastic Antifreeze Proteins of Deschampsia antarctica as Enhancer of Common Cell Freezing Media for Cryobanking of Genetic Resources, a Preliminary Study.

Antifreeze proteins (AFPs) are natural biomolecules found in cold-adapted organisms that lower the freezing point of water, allowing survival in icy conditions. These proteins have the potential to improve cryopreservation techniques by enhancing the quality of genetic material postthaw. Deschampsia antarctica, a freezing-tolerant plant, possesses AFPs and is a promising candidate for cryopreservation applications. In this study, we investigated the cryoprotective properties of AFPs from D. antarctica extracts on Atlantic salmon spermatozoa. Apoplastic extracts were used to determine ice recrystallization inhibition (IRI), thermal hysteresis (TH) activities and ice crystal morphology. Spermatozoa were cryopreserved using a standard cryoprotectant medium (C+) and three alternative media supplemented with apoplastic extracts. Flow cytometry was employed to measure plasma membrane integrity (PMI) and mitochondrial membrane potential (MMP) postthaw. Results showed that a low concentration of AFPs (0.05 mg/mL) provided significant IRI activity. Apoplastic extracts from D. antarctica demonstrated a cryoprotective effect on salmon spermatozoa, with PMI comparable to the standard medium. Moreover, samples treated with apoplastic extracts exhibited a higher percentage of cells with high MMP. These findings represent the first and preliminary report that suggests that AFPs derived from apoplastic extracts of D. antarctica have the potential to serve as cryoprotectants and could allow the development of novel freezing media.

Can Mecsina Hemostopper, which has a Cytotoxic Effect on Mcf-7 Cells, be Considered an Anticarcinogenic Agent due to its Immunological Properties?

Aim: Mecsina is used as a hemostatic agent such as Ankaferd and Tranexamic acid. To struggle with breast cancer, which is a serious public health issue, new, effective, and less toxic therapeutic agents are needed. Hence, it is aimed to compare and evaluate the effects of Mecsina and Ankaferd, both of which contain natural biomolecules in their structure, and synthetic Tranexamic acid on MCF-7 cells.
 Material and Method: For this study, MCF-7 immortalized cell lines were commercially purchased. The cells, 5000 cells per flask for each different dose group, were distributed to the 9 groups (mecsina 1:1, 1:2, 1:10, 1:50, 1:100, 1:200, 1:500, distilled water administered negative and control without any administration). Cytotoxicity, ELISA cytokine levels were evaluated, and flow cytometric analyzes were performed for each group using the XTT analysis method, after 24 hours of incubation.
 Results: A significant difference was observed between different doses of drug administration groups of Mecsina Hemostopper hemostatic agent in MCF-7 cells (p

Hyaluronan – A multipotent biomolecule in the field of medicine

Hyaluronan, a natural biomolecule, has immense potential in the field of medicine. This glycosaminoglycan present naturally in the human body and seen more in connective tissue, skin, and eyes essentially functions as lubricant and helps strengthen bones. Hyaluronan supplements have been used for a plethora of medical applications including cancer and osteoarthritis therapy, wound healing, and regenerative medicine. The revolutionary discoveries in the field of nanotechnology and biopolymers have indeed paved the way for better and more precise uses of hyaluronan by way of newer designs and composites for improved drug efficacy. At the same time, caution has to be exercised, as few recent studies imply the positive role of low molecular weight hyaluronic acid in the progression of some cancers. The present review elaborates on the range of existing applications across various fields ranging from medical treatment to organ development, and sheds light on the possibilities of maximizing its effectiveness.

Synthesis and characterization of new electrospun medical scaffold-based modified cellulose nanofiber and bioactive natural propolis for potential wound dressing applications.

Recently, the design of polymer nanofibers using the electrospinning process has attracted much interest. Particularly the use of natural polymers has promoted many advantages in their biomedical applications. However, the combination of multiple natural polymers remains a great challenge in terms of electrospun production and applied performance. From this perspective, the current investigation highlights the study of the preparation of electrospun nanomaterial scaffolds based on combined natural polymers for improved wound healing performance. First, we have synthesized a crosslinked polymer by reacting microcrystalline cellulose (MC) and chitosan (CS) biopolymer via the intermediate of citric acid as a crosslinking agent. Then a natural propolis biomolecule was incorporated into the polymer network. Different MC/CS blend ratios of 90/10 and 70/30 were then used and various machine parameters were optimized to obtain nanofiber scaffolds with excellent strength and structures. SEM, IR, physicochemical, mechanical, and morpho-logical characterization were then performed. SEM evaluation revealed homogeneous and bead-free nanofibrous structures, with well-defined morphology and a random deposition that could accurately mimic the extracellular matrix of native skin. The calculated average nanofiber diameters for the MC/CS blend ratios at 90/10 and 70/30 were 431.4 and 441.2 nm, respectively. The results showed that when the chitosan amount increased, larger nanofibers with narrow diameter distribution appeared. The prepared nanomaterials had a significant and close water vapor permeability of about 1735.12 and 1698.52 g per m per day for the two blend ratios of 90/10 and 70/30, respectively. The examination of swelling behavior revealed a noteworthy enhancement in hydrophilicity, a necessary attribute for improved healing efficacy. FT-IR analysis confirmed the success and the stability of the chemical crosslinking reaction between the two biopolymers before nanofiber conception. Excellent mechanical properties were acquired, based on the chitosan content. Both developed nanofiber scaffolds exhibited high tensile strength and Young's modulus values. The incorporation of 30% chitosan versus 10% results in an increase in tensile strength of 11% and 14% in Young's modulus. Therefore, we could adjust the different mechanical properties simply by varying the mixing rate of the electrospun polymers. Using epithelial HepG2 cells, viability and kinetic cell adhesion assays were assessed to obtain biological evaluation. No cytotoxicity was observed and good cytocompatibility was confirmed. Functionalized nanofiber biomaterials with different MC/CS ratios substantiated significant bactericidal effectiveness against Gram-positive and Gram-negative bacterial culture strains. The novel functional electrospun wound dressing scaffold demonstrated effective and promising biomedical performance, healing both acute and chronic wounds.

"Gear-driven"-type chirality transfer of tetraphenylethene-based supramolecular organic frameworks for peptides in water.

Chirality transfer for natural chiral biomolecules can reveal the indispensable role of chiral structures in life and can be used to develop the chirality-sensing biomolecular recognition. Here, we report the synthesis and characterization of a series of achiral supramolecular organic frameworks (SOF-1, SOF-2, and SOF-3), constructed from cucurbit[8]uril (CB[8]) and tetraphenylethene (TPE) derivatives (1, 2, and 3), respectively, as chirality-sensing platforms to explore their chirality transfer mechanism for peptides in water. Given the right-handed (P) and left-handed (M) rotational conformation of TPE units and the selective binding of CB[8] to aromatic amino acids, these achiral SOFs can be selectively triggered in water by peptides containing N-terminal tryptophan (W) and phenylalanine (F) residues into their P- or M-rotational conformation, exhibiting significantly different circular dichroism (CD) spectra. Although various peptides have the same l-type chiral configuration, they can induce positive CD signals of SOF-1 and negative CD signals of SOF-2 and SOF-3, respectively. Based on the structural analysis of the linkage units between CB[8] and TPE units in these SOFs, a "gear-driven"-type chirality transfer mechanism has been proposed to visually illustrate the multiple-step chirality transfer process from the recognition site in the CB[8]'s cavity to TPE units. Furthermore, by utilizing the characteristic CD signals generated through the "gear-driven"-type chirality transfer, these SOFs can serve as chiroptical sensor arrays to effectively recognize and distinguish various peptides based on their distinctive CD spectra.

Natural Biomolecules in Leaves and Fruit Extracts Mediate the Biosynthesis of SnO2 Nanoparticles: A Mini Review

Natural Biomolecules in Leaves and Fruit Extracts Mediate the Biosynthesis of SnO2 Nanoparticles: A Mini Review

In Silico Molecular Docking Analysis of Selected Natural Biomolecules on Nitric Oxide Synthase

In Silico Molecular Docking Analysis of Selected Natural Biomolecules on Nitric Oxide Synthase

Preparation, characterization, and toxicity evaluation of microemulsion formulation containing prunetin for potential oral applications

Phytochemicals as therapeutic alternatives can have a fundamental impact on the various stages of inflammation and its resolution. Prunetin is a naturally occurring isoflavone and has been claimed to have numerous therapeutic potentials. The objective of this study is preparation, characterization, and toxicity evaluation of microemulsion formulation containing prunetin (PMF) for potential oral applications. With this research, it was targeted to emphasize the way of improving the therapeutic efficacy of natural biomolecules with a nontoxic and effective formulation. In the study, the pseudo-ternary phase diagram was developed and PMF was characterized by conductivity, droplet size, viscosity and pH. Effects against to cytokines (IL-1β and IL-6) and TNF-α levels of the PMF were determined by ELISA technique. Genotoxicity and acute oral toxicity tests were carried out according to OECD guidelines. The results showed that PMF is a colloid system that reduced proinflammatory cytokine levels in LPS-induced macrophage cells compared to the control group. PMF demonstrated no mutagenic activity against TA98, TA100, TA1535, and TA1537 Salmonella strains. The in vivo oral acute toxicity test results indicated that PMF did not show mortality or significant side effects even at 2000 mg/kg bw. This study represents PMF showed a good safety profile in animal study. It is thought that this formulation may have anti-inflammatory potential with further in vivo testing.

The recent research progress of polyphenol‐derived biomaterials in wound repair

AbstractThe clinical requirements for wound care are increasing daily, and the global wound dressing market is expanding; however, the research and development of new wound dressings are imminent. Natural biomolecules such as polyphenols, have been widely used in this field of vision. Owing to their unique anti‐oxidative, adhesive, antibacterial and other bioactive functions, researchers have developed a series of wound dressings with excellent performance and applied them to a variety of biomaterials, such as hydrogels, nanofibers, films and scaffolds. They can effectively promote angiogenesis and fibroblast migration and proliferation, scavenge active oxygen free radicals, inhibit excessive inflammatory reactions at wound sites and ultimately accelerate wound healing. The authors summarise the latest progress in polyphenol‐derived biomaterials in skin wound repair to provide inspiration for future wound dressing research.

Supramolecular Nanostructures for the Delivery of Peptides in Cancer Therapy.

Supramolecular nanostructured based delivery systems are emerging as a meaningful approach in the treatment of cancer, offering controlled drug release and improved therapeutic efficacy. The self-assembled structures can be small molecules, polymers, peptides, or proteins, which can be used and functionalized to achieve tailored release and target specific cells, tissues, or organs. These structures can improve the solubility and stability of drugs having low aqueous solubility by encapsulating and protecting them from degradation. Alongside, peptides as natural biomolecules have gained increasing attention as potential candidates in cancer treatment because of their biocompatibility, low cytotoxicity, and high specificity toward tumor cells. The amino acid sequences in peptide molecules are tunable, efficiently controlling the morphology of peptide-based self-assembled nanosystems and offering flexibility to form supramolecular nanostructures (SNs). It is evident from the current literature that the supramolecular nanostructures based delivery of peptide for cancer treatment hold great promise for future cancer therapy, offering potential strategies for personalized medicine with improved patient outcomes. SIGNIFICANCE STATEMENT: This review focuses on fundamentals and various drug delivery mechanisms based on SNs. Different SN approaches and recent literature reviews on peptide delivery are also presented to the readers.

A review of glycosaminoglycan-modified electrically conductive polymers for biomedical applications.

The application areas of electrically conductive polymers have been steadily growing since their discovery in the late 1970s. Recently, electrically conductive polymers have found their way into biomedicine, allowing the realization of many relevant applications ranging from bioelectronics to scaffolds for tissue engineering. Extracellular matrix components, such as glycosaminoglycans, build an important class of biomaterials that are heavily researched for biomedical applications due to their favorable properties. Due to their highly anionic character and the presence of sulfate groups in glycosaminoglycans, these biomolecules can be employed to functionalize conductive polymers, which enables the tailorability and improvement of cell-material interactions of conductive polymers. This review paper gives an overview of recent research on glycosaminoglycan-modified conductive polymers intended for biomedical applications and discusses the effect of different biological dopants on material characteristics, such as surface roughness, stiffness, and electrochemical properties. Moreover, the key findings of the biological characterization in vitro and in vivo are summarized, and remaining challenges in the field, particularly related to the modification of electrically conductive polymers with glycosaminoglycans to achieve improved functional and biological outcomes, are discussed. STATEMENT OF SIGNIFICANCE: The development of functional biomaterials based on electrically conductive polymers (CPs) for various biomedical applications, such as neural regeneration, drug delivery, or bioelectronics, has been increasingly investigated over the last decades. Recent literature has shown that changes in the synthesis procedure or the chosen dopant could adjust the resulting material characteristics. Hence, an interesting approach lies in using natural biomolecules as dopants for CPs to tailor the biological outcome. This review comprehensively summarizes the state of the art in the field of glycosaminoglycan-modified electrically conductive polymers for the first time, particularly highlighting the effect of the chosen dopant on material characteristics, such as surface morphology or stiffness, electrochemical properties, and consequently, cell-material interactions.

Antipathogenic potentials of exopolysaccharides produced by lactic acid bacteria and their food and health applications

In the recent years, there has been increased interest in the exopolysaccharides (EPS) of microbial origin, especially the EPS produced by lactic acid bacteria (LAB). These EPS exhibit considerable structural and physico-chemical diversities with numerous potential applications. The biological and functional potentials of LAB EPS include antioxidant, anti-microbial, anti-cancer, wound healing, immunomodulatory and prebiotic properties. With increased interest in natural and eco-friendly biomolecules as tools in the management of food quality and safety, biomolecules such as EPS of microbial origin are being evaluated. Although there are many reviews on the biological and functional properties of EPS, in this review we particularly focused on the anti-bacterial, anti-fungal, anti-viral and anti-biofilm properties of the EPS of LAB origin. Modes and mechanisms of action by which EPS interacts with the pathogens (bacteria, bacterial biofilm, fungi, and virus) to inhibit or kill them are also discussed. The anti-microbial effects of EPS have the potential to play a vital role in food preservation as well as protection which can be exploited effectively. Interestingly EPS has beneficial effects on gut homeostasis through modulating gut microbiota, inhibiting pathogens, and preventing bacterial as well as viral infections. The role of LAB EPS in food safety and human health vis-à-vis their applications in food and pharmaceutical industries are discussed in this review. However, more studies are required for maximum utility of these bio-functional EPS potentials for food preservation, food safety and other health claims.

Antimicrobial, antioxidant, and cytotoxic properties of endophytic fungi isolated from Thysanolaena maxima Roxb., Dracaena spicata Roxb. and Aglaonema hookerianum Schott.

BackgroundEndophytic fungi have recently been recognized as an impressive source of natural biomolecules. The primary objective of the research was to isolate fungal endophytes from Thysanolaena maxima Roxb., Dracaena spicata Roxb. and Aglaonema hookerianum Schott. of Bangladesh and assess their pharmacological potentialities focusing on antimicrobial, antioxidant, and cytotoxic properties.MethodsThe fungal isolates were identified up to the genus level by analyzing their macroscopic and microscopic characteristics. Ethyl acetate extracts of all the fungal isolates were screened for different bioactivities, including antimicrobial (disc diffusion method), antioxidant (DPPH scavenging assay), and cytotoxic (brine shrimp lethality bioassay) activities.ResultsAmong the thirteen isolates, Fusarium sp. was the most recognized genus, while the others belonged to Colletotrichum sp. and Pestalotia sp. Comparing the bioactivity of all the extracts, Fusarium sp. was shown to be the most effective endophyte, followed by Colletotrichum sp. and Pestalotia sp. In the antimicrobial study, two isolates of Fusarium sp. (internal strain nos. DSLE-1 and AHPE-4) showed inhibitory activity against all the tested bacteria and the highest zone of inhibition (15.5 ± 0.4 mm) was exerted by AHPE-4 against Bacillus subtillis. All the fungal isolates produced mild to moderate free radical scavenging activity, where the highest antioxidant activity was revealed by one isolate of Fusarium sp. (internal strain no. AHPE-3) with an IC50 value of 84.94 ± 0.41 µg/mL. The majority of Fusarium sp. isolates exhibited notable cytotoxic activity, where AHPE-4 exhibited the highest cytotoxicity, having the LC50 value of 14.33 ± 4.5 µg/mL.ConclusionThe findings of the study endorsed that the fungal endophytes isolated from T. maxima, D. spicata, and A. hookerianum hold potential as valuable origins of bioactive substances. Nevertheless, more comprehensive research is warranted, which could develop novel natural compounds from these endophytes to treat various infectious and cancerous diseases.

Pectin encapsulated novel nanocomposite augments wound healing in Sprague Dawley rats

The complexity of the tissue remodeling process makes the treatment options for wound healing inadequate. Herein, the potential wound-healing activity of a novel nanocomposite with pectin and keratin incorporating silver nanoparticles and ferulic acid has been evaluated. Silver concentration, secondary structural stability of keratin, and the presence of ferulic acid and nano silver as a complex molecule within the nanocomposite were confirmed by XPS, CD spectroscopy, and ESI-MS analysis, respectively. The effects of the nanocomposite (NC) on cell migration and the role of apoptosis in wound healing were studied by scratch assay and (A.O./EtBr) staining, respectively. Subsequently, in vivo studies were carried out in male Sprague Dawley rats. Wound tracings measured exhibited significant wound contraction. Further, the relative gene expression of wound–healing biomarkers MMP2, MMP8, and KGF increased considerably in the 75 mg test group compared to the negative control group indicating a faster epithelialization phase of wound healing. Histopathological observations revealed remarkable skin regeneration in the test group. Altogether, the nanocomposite at 75 mg dose exhibits enhanced cell migration capability, reepithelialization and tissue remodeling activity than the standard, possibly due to the synergistic influence of the natural biomolecules. Therefore it is concluded that the NC exhibits accelerated wound healing with negligible toxicity.

Micelle encapsulated curcumin and piperine-laden 3D printed calcium phosphate scaffolds enhance in vitro biological properties

Limitations in the current clinical management of critical-sized osseous defects have driven the need for multifunctional bone constructs. The ideal bone scaffold should possess advanced microarchitecture, well-defined pore interconnectivity, and supply biological signals, which actively guide and control tissue regeneration while simultaneously preventing post-implantation complications. Here, a natural medicine-based localized drug delivery from 3D printed scaffold is presented, which offers controlled release of curcumin, piperine from nano-sized polymeric micelles, and burst release of antibacterial carvacrol from the coating endowing the scaffold with their distinct, individual biological properties. This functionalized scaffold exhibits improved osteoblast (hFOB) cell attachment, 4-folds higher hFOB proliferation, and 73% increased hFOB differentiation while simultaneously providing cytotoxicity towards osteosarcoma cells with 61% lesser viability compared to control. In vitro, early tube formation (p < 0.001) indicates that the scaffolds can modulate the endothelial cellular network, critical for faster wound healing. The scaffold also exhibits 94% enhanced antibacterial efficacy (p < 0.001) against gram-positive Staphylococcus aureus, the main causative bacteria for osteomyelitis. Together, the multifunctional scaffolds provide controlled delivery of natural biomolecules from the nano-sized micelle-loaded 3D printed matrix for significant improvement in osteoblast proliferation, endothelial formation, osteosarcoma, and bacterial inhibition, guiding better bone regeneration for post-traumatic defect repair.