Silver Nanoparticle-Embedded Carbon Nitride: Antifungal Activity on Candida albicans and Toxicity toward Animal Cells.

The development of engineered nanomaterials has been considered a promising strategy to control oral infections. In this study, silver-embedded carbon nitrides (Ag@g-CN) were synthesized and tested against Candida albicans, investigating their antifungal action and biocompatibility in animal cells. Ag@g-CN was synthesized by a simple one-pot thermal polymerization technique and characterized by various analytical techniques. X-ray diffraction (XRD) analysis revealed slight alterations in the crystal structure of g-CN upon the incorporation of Ag. Fourier transform infrared (FT-IR) spectroscopy confirmed the presence of Ag-N bonds, indicating successful silver incorporation and potential interactions with g-CN's amino groups. UV-vis spectroscopy demonstrated a red shift in the absorption edge of Ag@g-CN compared with g-CN, attributed to the surface plasmon resonance effect of silver nanoparticles. Field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) confirmed the 2D layered sheet like morphology of both materials. The Ag 3d peaks found in X-ray photoelectron spectroscopy (XPS) confirmed the presence of metallic Ag0 nanoparticles in Ag@g-CN. The Ag@g-CN materials exhibited high antifungal activity against reference and oral clinical strains of C. albicans, with minimal inhibitory concentration (MIC) ranges between 16-256 µg/mL. The mechanism of Ag@g-CN on C. albicans was attributed to the disruption of the membrane integrity and disturbance of the biofilm. In addition, the Ag@g-CN material showed good biocompatibility in the fibroblastic cell line and in Galleria mellonella, with no apparent cytotoxicity observed at a concentration up to 1000 µg/mL. These findings demonstrate the potential of the Ag@g-CN material as an effective and safe antifungal agent for the treatment of oral fungal infections.

On-demand release of a selective MMP-13 blocker from an enzyme-responsive injectable hydrogel protects cartilage from degenerative progression in osteoarthritis.

In osteoarthritis (OA), the degradation of cartilage is primarily driven by matrix metalloprotease-13 (MMP-13). Hence, the inhibition of MMP-13 has emerged as an attractive target for OA treatment. Among the various approaches that are being explored for MMP-13 regulation, blocking of the enzyme with specific binding molecules appears to be a more promising strategy for preventing cartilage degeneration. To enhance effectiveness and ensure patient compliance, it is preferable for the binding molecule to exhibit sustained activity when administered directly into the joint. Herein, we present an enzyme-responsive hydrogel that was designed to exhibit on-demand, the sustained release of BI-4394, a potent and highly selective MMP-13 blocker. The stable and compatible hydrogel was prepared using triglycerol monostearate. The efficacy of the hydrogel to prevent cartilage damage was assessed in a rat model of OA induced by anterior cruciate ligament transection (ACLT). The results revealed that in comparison to the rats administrated weekly with intra-articular BI-4394, the hydrogel implanted rats had reduced levels of inflammation and bone erosion. In comparison to untreated control, the cartilage in animals administered with BI-4394/hydrogel exhibited significant levels of collagen-2 and aggrecan along with reduced MMP-13. Overall, this study confirmed the potential of BI-4394 delivery using an enzyme-responsive hydrogel as a promising treatment option to treat the early stages of OA by preventing further cartilage degradation.

Investigating wound healing potential of sesamol loaded solid lipid nanoparticles: Ex-vivo, in vitro and in-vivo proof of concept.

Sesamol, a lignan, obtained from sesame seeds (Sesamum indicum Linn., Pedaliaciae) has a promising antioxidant, and anti-inflammatory profile. When applied topically, free sesamol rapidly crosses skin layers and gets absorbed in systemic circulation. Its encapsulation into solid lipid nanoparticles not only improved its localised delivery to skin but also resulted in better skin retention, as found in ex-vivo skin retention studies. Free and encapsulated sesamol was compared for antimicrobial and antibiofilm activity against some common skin pathogens and it was found that encapsulation improved the antimicrobial profile by 200%. In vivo evaluation in diabetic open excision wound model suggested that encapsulation of sesamol in SLNs substantially enhanced its wound healing potential when investigated for biophysical, biochemical and histological parameters. It was envisaged that this was achieved via inhibiting bacterial growth and clearing the bacterial biofilm at the wound site, and by regulating oxidative stress in skin tissue.

Biocidal polymer derived near white light-emitting polymeric carbon particles for antibacterial and bioimaging applications.

A growing antimicrobial crisis has increased demand for antimicrobial materials. It has become increasingly popular to convert polymeric macromolecules into polymeric carbon particles (PCP) in order to achieve highly biocompatible materials with unique properties as a result of the ability to synthesize nanomaterials of the right size and add value to existing stable polymers. This work presents the tuning of PCP for antibacterial application by combining a biocidal polymer with one-pot solvothermal synthesis. PCP displayed broad-spectrum antibacterial activity via various mechanisms, including inhibition of bacterial cell walls, ROS generation, and antibiotic resistance. Furthermore, these biocidal PCP were observed to show excitation-independent near-white light emission which on the other hand is generally possible due to mixed sizes, doping, and surface effects. As opposed to the parent biocidal polymer, PCP added ROS-mediated bactericidal activity, increased cytocompatibility, and nanofibers with anti-adhesive effects and potential of imaging bacterial cells.

Efficient Nitric Oxide Scavenging by Urea-Functionalized Push-Pull Chromophore Modulates NO-Mediated Diseases.

The excess nitric oxide (NO) produced in the body in response to bacterial/proinflammatory stimuli is responsible for several pathological conditions. The current approaches that target the production of excess NO, either through the inhibition of nitric oxide synthase enzyme or its downstream mediators have been clinically unsuccessful. With an aim to regulate the excess NO, urea-functionalized push-pull chromophores containing 1,1,4,4-tetracyanobuta-1,3-dienes (TCBD) or expanded TCBD (eTCBD) were developed as NO scavengers. The NMR mechanistic studies revealed that upon NO binding, these molecules are converted to uncommon stable NONOates. The unique emissive property of Urea-eTCBD enables its application in vitro, as a NO-sensor. Furthermore, the cytocompatible Urea-eTCBD, rapidly inactivated the NO released from LPS-activated cells. The therapeutic efficacy of the molecule in modulating NO-mediated pathological condition was confirmed using a carrageenan-induced inflammatory paw model and a corneal injury model. While the results confirm the advantages of scavenging the excess NO to address a multitude of NO-mediated diseases, the promising sensing and bioactivity of Urea-eTCBD can motivate further exploration of such molecules in allied areas of research.

Free-flowing, self-crosslinking, carboxymethyl starch and carboxymethyl cellulose microgels, as smart hydrogel dressings for wound repair.

Hydrogels are widely recognized and favoured as moist wound dressings due to their beneficial properties. However, their limited capacity to absorb fluids restricts their use in highly exuding wounds. Microgels are small sized hydrogels that have recently gained considerable attention in drug delivery applications due to their superior swelling behaviour and ease of application. In this study, we introduce dehydrated microgel particles (µGeld) that rapidly swell and interconnect, forming an integrated hydrogel when exposed to fluid. These free-flowing microgel particles, derived from the interaction of carboxymethylated forms of starch and cellulose, have been designed to significantly absorb fluid and release silver nanoparticles in order to effectively control infection. Studies using simulated wound models validated the microgels ability to efficiently regulate the wound exudate and create a moist environment. While the biocompatibility and hemocompatibility studies confirmed the safety of the µGel particles, its haemostatic property was established using relevant models. Furthermore, the promising results from a full-thickness wounds in rats have highlighted the enhanced healing potential of the microgel particles. These findings suggest that the dehydrated microgels can evolve as a new class of smart wound dressings.

Post-Implantation Stiffening by a Bioinspired, Double-Network, Self-Healing Hydrogel Facilitates Minimally Invasive Cell Delivery for Cartilage Regeneration.

Injectable hydrogels have demonstrated advantages in cartilage repair by enabling the delivery of cells through a minimally invasive approach. However, several injectable hydrogels suffer from rapid degradation and low mechanical strength. Moreover, higher mechanical stiffness in hydrogels can have a detrimental effect on post-implantation cell viability. To address these challenges, we developed an in situ forming bioinspired double network hydrogel (BDNH) that exhibits temperature-dependent stiffening after implantation. The BDNH mimics the microarchitecture of aggrecan, with hyaluronic acid-conjugated poly(N-isopropylacrylamide) providing rigidity and Schiff base crosslinked polymers serving as the ductile counterpart. BDNHs exhibited self-healing property and enhanced stiffness at physiological temperature. Excellent cell viability, long time cell proliferation, and cartilage specific matrix production were observed in the chondrocytes cultured in the BDNH hydrogel. Evidence of cartilage regeneration in a rabbit cartilage defect model using chondrocyte-laden BDNH has suggested it to be a potential candidate for cartilage tissue engineering.

Injectable Bone Cement Reinforced with Gold Nanodots Decorated rGO-Hydroxyapatite Nanocomposites, Augment Bone Regeneration.

Interest in the development of new generation injectable bone cements having appropriate mechanical properties, biodegradability, and bioactivity has been rekindled with the advent of nanoscience. Injectable bone cements made with calcium sulfate (CS) are of significant interest, owing to its compatibility and optimal self-setting property. Its rapid resorption rate, lack of bioactivity, and poor mechanical strength serve as a deterrent for its wide application. Herein, a significantly improved CS-based injectable bone cement (modified calcium sulfate termed as CSmod ), reinforced with various concentrations (0-15%) of a conductive nanocomposite containing gold nanodots and nanohydroxyapatite decorated reduced graphene oxide (rGO) sheets (AuHp@rGO), and functionalized with vancomycin, is presented. The piezo-responsive cement exhibits favorable injectability and setting times, along with improved mechanical properties. The antimicrobial, osteoinductive, and osteoconductive properties of the CSmod cement are confirmed using appropriate in vitro studies. There is an upregulation of the paracrine signaling mediated crosstalk between mesenchymal stem cells and human umbilical vein endothelial cells seeded on these cements. The ability of CSmod to induce endothelial cell recruitment and augment bone regeneration is evidenced in relevant rat models. The results imply that the multipronged activity exhibited by the novel-CSmod cement would be beneficial for bone repair.

Natural sunlight driven photocatalytic dye degradation by biogenically synthesized tin oxide (SnO2) nanostructures using Tinospora crispa stem extract and its anticancer and antibacterial applications.

In the present study, tin oxide (SnO2) was synthesized by advocating the principles of green chemistry for the photo-mediated degradation of pollutants, antimicrobial, and as an antitumor agent. Bioactive SnO2 (nanorods & nanospheres) were fabricated using Tinospora crispa stem extract (TCSE) via sol-gel technique and characterized extensively. XRD, UV-VIS, FTIR, and XPS studies confirmed the formation of crystalline and well stoichiometric pure phase of SnO2 nanostructures with optical bandgap 3.2 to 3.5 eV. The transmission electron microscopy (TEM) results demonstrated the effect of secondary phytoconstituents on the shape of SnO2 in a concentration dependent manner. The morphological variations in the obtained nanostructures attributed to the nucleation density and coalescence effect leading to the formation of nanorods with an average diameter 23-25 nm whereas the average particle size of the nanospheres obtained was found to be 23-30 nm. The zeta potential value of SnO2 nanorods was high (- 58.9 mV) indicating the higher stability compared to nanospheres (- 15.6 mV). The SnO2 nanostructures were investigated for the simultaneous degradation of methylene blue with degradation efficiency of 92.3% and 47.3% for rhodamine B in mono system and 72.3%, 47.7% respectively for binary dye system. The anticancer activity of SnO2 nanorods explored against human breast cancer (MCF-7) cells revealed a concentration dependent cytotoxic effect reactive oxygen species (ROS) induced cell death. Additionally, efficient antibacterial activity of SnO2 was established using E.coli. Multifaceted applications of Tinospora crispa stem extract mediated SnO2 nanostructures.

Protease-responsive hydrogel, cross-linked with bioactive curcumin-derived carbon dots, encourage faster wound closure.

The pharmacological effects of curcumin can be ascribed to its dose-dependent activity. Therapeutic application of curcumin is hindered by its poor solubility and low bioavailability. Carbon dots are gaining attention in biomedical applications in view of their unique photo-physical properties. Some carbon dots derived from bioactive molecules have shown superior activity than the parent compound. With an aim to address the limitations of curcumin, herein we compared the wound healing activity of curcumin-derived carbon dots (CurCD) with curcumin. The improved solubility and stability of CurCD, combined with its superior proliferative, proangiogenic and anti-bacterial activity suggested that CurCD would be more beneficial than curcumin in wound healing. To enable the sustained release of CurCD at the wound site, a protease-responsive hydrogel (GHCD) was prepared with CurCD acting as a cross-linker. A comparative study using a skin excision model revealed that GHCD supported faster wound closure with improved angiogenesis and complete restoration of the epithelium. Apart from the establishment of CurCD as a wound healing agent, the study provides a novel carbon dot based approach for molecules with limitations of solubility and bioavailability.

A drug-free strategy to combat bacterial infections with magnetic nanoparticles biosynthesized in bacterial pathogens.

The extensive and indiscriminate use of antibiotics in the ongoing COVID-19 pandemic might significantly contribute to the growing number of multiple drug resistant (MDR) bacteria. With the dwindling pipeline of new and effective antibiotics, we might soon end up in a post-antibiotic era, in which even common bacterial infections would be a challenge to control. To prevent this, an antibiotic-free strategy would be highly desirable. Magnetic nanoparticle (MNP)-mediated hyperthermia-induced antimicrobial therapy is an attractive option as it is considered safe for human use. Given that iron and zinc are critical for bacterial virulence, we evaluated the response of multiple pathogenic bacteria to these elements. Treatment with 1 mM iron and zinc precursors resulted in the intracellular biosynthesis of MNPs in multiple Gram-positive and Gram-negative disease-causing bacteria. The superparamagnetic nanoparticles in the treated bacteria/biofilms, generated heat upon exposure to an alternating magnetic field (AMF), which resulted in an increase in the temperature (5-6 °C) of the milieu with a subsequent decrease in bacterial viability. Furthermore, we observed for the first time that virulent bacteria derived from infected samples harbour MNPs, suggesting that the bacteria had biosynthesised the MNPs using the metal ions acquired from the host. AMF treatment of the bacterial isolates from the infected specimens resulted in a strong reduction in viability (3-4 logs) as compared to vancomycin/ciprofloxacin treatment. The therapeutic efficacy of the MNPs to induce bacterial death with AMF alone was confirmed ex vivo using infected tissues. Our proposed antibiotic-free approach for killing bacteria using intracellular MNPs is likely to evolve as a promising strategy to combat a wide range of bacterial infections.

Molecular docking and molecular dynamics to identify collagenase inhibitors as lead compounds to address osteoarthritis.

Osteoarthritis (OA) is a degenerative disease which affects a large number of individuals. Collagenases, which belong to a class of metalloproteases (MMPs), are responsible for the degradation of cartilage manifested in OA. Inhibition of the catalytic domains of these MMPs is one of the important therapeutic strategies proposed for the prevention of OA. The main objective of this work is to evaluate the binding of curcumin and its metabolites with the active sites of collagenases in comparison to standard inhibitors on the basis of our hypothesis that curcumin/metabolites could exhibit an inhibitory effect on MMPs. Here, we report the molecular docking analysis of curcumin and its metabolites with collagenases (MMP-1, MMP-8, MMP-13). Among the molecules tested, curcumin monoglucuronide (CMG) demonstrated the best binding affinity with MMP-13, which is specifically implicated in OA. The CMG-MMP-complexes were further subjected to molecular dynamic simulations to explore the stability of the complexes and to estimate the free binding energies. The results indicated that CMG preferentially bind to MMP-13 in comparison to that of MMP-1 and MMP-8 with binding free energies (ΔGbind) of (-60.55), (-27.02) and (-46.91) kcal/mol, respectively. This is the first study which suggests that curcumin monoglucuronide can be considered as an effective lead compound to prevent the progression of OA.Communicated by Ramaswamy H. Sarma.

Mechanical Integrity in a Dynamic Interpenetrating Hydrogel Network of Supramolecular Peptide-Polysaccharide Supports Enhanced Chondrogenesis.

Tissue engineering demands intelligently designed scaffolds that encompass the properties of the target tissues in terms of mechanical and bioactive properties. An ideal scaffold for engineering a cartilage tissue should provide the chondrocytes with a favorable 3D microarchitecture apart from possessing optimal mechanical characteristics such as compressibility, energy dissipation, strain stiffening, etc. Herein, we used a unique design approach to develop a hydrogel having a dynamic interpenetrating network to serve as a framework to support chondrocyte growth and differentiation. An amyloid-inspired peptide amphiphile (1) was self-assembled to furnish kinetically controlled nanofibers and incorporated in a dynamic covalently cross-linked polysaccharide network of carboxymethyl cellulose dialdehyde (CMC-D) and carboxymethyl chitosan (CMCh) using Schiff base chemistry. The dynamic noncovalent interaction played a pivotal role in providing the desired modulation in the structure and mechanical properties of the double-network hydrogels that are imperative for cartilage scaffold design. The adaptable nature supported shear-induced extrusion of the hydrogel and facilitated various cellular functions while maintaining its integrity. The potential of the as-developed hydrogels to support in vitro chondrogenesis was explored using human chondrocytes. Evidence of improved cell growth and cartilage-specific ECM production confirmed the potential of the hydrogel to support cartilage tissue engineering while reaffirming the significance of mimicking the biophysical microenvironment to induce optimal tissue regeneration.

An injectable hydrogel having proteoglycan-like hierarchical structure supports chondrocytes delivery and chondrogenesis.

The ECM of cartilage is composed of proteoglycans (PG) that contain glycosaminoglycan (GAG), aggrecan, hyaluronic acid (HA) and other molecular components which play an important role in regulating chondrocyte functions via cell-matrix interactions, integrin-mediated signalling etc. Implantation of chondrocytes encapsulated in scaffolds that mimic the micro-architecture of proteoglycan, is expected to enhance cartilage repair. With an aim to create a hydrogel having macromolecular structure that resembles the cartilage-specific ECM, we constructed a hierarchal structure that mimic the PG. The bottle brush structure of the aggrecan was obtained using chondroitin sulphate and carboxymethyl cellulose which served as GAG and core protein mimic respectively. A proteoglycan-like structure was obtained by cross-linking it with modified chitosan that served as a HA substitute. The physico-chemical characteristics of the above cross-linked injectable hydrogel supported long term human articular chondrocyte subsistence and excellent post-injection viability. The chondrocytes encapsulated in the PMH expressed significant levels of articular cartilage specific markers like collagen II, aggrecan, GAGs etc., indicating the ability of the hydrogel to support chondrocyte differentiation. The biocompatibility and biodegradability of the hydrogels was confirmed using suitable in vivo studies. The results revealed that the PG-mimetic hydrogel could serve as a promising scaffold for chondrocyte implantation.

Tunable, conductive, self-healing, adhesive and injectable hydrogels for bioelectronics and tissue regeneration applications.

Conductive hydrogels are attracting considerable interest in view of their potential in a wide range of applications that include healthcare and electronics. Such hydrogels are generally incorporated with conductive materials/polymers. Herein, we present a series of conductive hydrogels (Ch-CMC-PDA), prepared with no additional conductive material. The hydrogels were synthesized using a combination of chitosan, cellulose (CMC) and dopamine (DA). The conductivity (0.01-3.4 × 10-3 S cm-1) in these gels is attributed to ionic conductivity. Very few conductive hydrogels are endowed with additional properties like injectability, adhesiveness and self-healing, which would help to widen their scope for applications. While the dynamic Schiff base coupling in our hydrogels facilitated self-healing and injectable properties, polydopamine imparted tissue adhesiveness. The porosity, rheological, mechanical and conductive properties of the hydrogels are regulated by the CMC-dialdehyde-polydopamine (CMC-D-PDA) content. The hydrogel was evaluated in various bioelectronics applications like ECG monitoring and triboelectric nanogenerators (TENG). The ability of the hydrogel to support cell growth and serve as a template for tissue regeneration was confirmed using in vitro and in vivo studies. In summary, the integration of such remarkable features in the ionic-conductive hydrogel would enable its usage in bioelectronics and biomedical applications.

SARS-CoV-2 and tissue damage: current insights and biomaterial-based therapeutic strategies.

The effect of SARS-CoV-2 infection on humanity has gained worldwide attention and importance due to the rapid transmission, lack of treatment options and high mortality rate of the virus. While scientists across the world are searching for vaccines/drugs that can control the spread of the virus and/or reduce the risks associated with infection, patients infected with SARS-CoV-2 have been reported to have tissue/organ damage. With most tissues/organs having limited regenerative potential, interventions that prevent further damage or facilitate healing would be helpful. In the past few decades, biomaterials have gained prominence in the field of tissue engineering, in view of their major role in the regenerative process. Here we describe the effect of SARS-CoV-2 on multiple tissues/organs, and provide evidence for the positive role of biomaterials in aiding tissue repair. These findings are further extrapolated to explore their prospects as a therapeutic platform to address the tissue/organ damage that is frequently observed during this viral outbreak. This study suggests that the biomaterial-based approach could be an effective strategy for regenerating tissues/organs damaged by SARS-CoV-2.

Recent advances in nanotherapeutic strategies that target nitric oxide pathway for preventing cartilage degeneration.

Nitric oxide (NO) is an important inflammatory mediator involved in the development and progression of osteoarthritis (OA). Increased production of NO in the affected joints promote cartilage damage. As NO synthesis is catalysed by the inducible NO synthase (iNOS) enzyme, iNOS inhibition serves as an attractive therapeutic target to prevent NO release. Despite a number of direct and indirect iNOS inhibitor molecules demonstrating chondro-protective effect, none have reached the clinic. Its limited bioavailability and adverse side effects served as a deterrent for pursuing clinical trials in OA patients. With the advent of nanotechnology, interest in targeting NO for preventing cartilage degeneration has revived. In this article, we discuss the limitations of the existing molecules and provide an insight on recent nanotechnology-based strategies that have been explored for the diagnosis and inhibition of NO in OA. These approaches hold promise in reviving the hitherto under explored potential of targeting NO to address OA.

Actin-binding carbon dots selectively target glioblastoma cells while sparing normal cells.

Curcumin, a pleiotropic signalling molecule from Curcuma longa, is reported to be effective against multiple cancers. Despite its promising effect, curcumin had failed in clinical trials due to its low aqueous solubility, stability and poor bioavailability. While several approaches are being attempted to overcome the limitations, the improved solubility observed with curcumin-derived carbon dots appeared to be a strategy worth exploring. To assess if the carbon dots possess bio-activity similar to curcumin, we synthesized carbon dots (CurCD) from curcumin and ethylenediamine. Unlike curcumin, the as-synthesized curcumin carbon dots exhibited excellent solubility, excitation-dependent emission and photostability. The anti-cancer activity evaluated with glioblastoma cells using the well-established in vitro models indicated its comparable/enhanced activity over curcumin. Besides, the selective affinity of CurCD to the actin filament, indicated it's prospective to serve as a marker of actin filaments. In addition, the non-toxic effects observed in normal cells and fish embryos indicated CurCD was more biocompatible than curcumin. While this work reveals the superior properties of CurCD over curcumin, it provides a new approach to explore other plant derived molecules with similar limitations like curcumin.

A bioinspired, ice-templated multifunctional 3D cryogel composite crosslinked through in situ reduction of GO displayed improved mechanical, osteogenic and antimicrobial properties.

3D biopolymeric scaffolds often lack the biochemical cues and mechanical strength to encourage bone tissue regeneration. Chemical crosslinkers have been extensively used to impart strength, but have been found to be toxic at the site of implantation and possess a lacuna in physical strength. We attempted to address this by engineering a self-crosslinked polymer through the in-situ reduction of Graphene oxide (GO) in a gelatin cryogel (Gel-RGO) using ice as a template to create pores. Superior osteoinductive and antimicrobial properties were further endowed on the cryogel by incorporating silver nanoparticles decorated nanohydroxyapatite in the Gel-RGOAg@Hap(2%) cryogel. The optimized biocompatible cryogel favoured bone cell adhesion and its proliferation. The osteoconductive and osteoinductive potential of the cryogel was confirmed through biomineralization and differentiation of bone cells. In addition, these cryogels showed prolonged antimicrobial activity against S. aureus. This investigation exhibits the achievability/prospect of building up an ideal gelatin platform without the utilization of an outside crosslinking agent via manipulating the conditions of gelation. The superior crosslinking achieved between gelatin and GO, in addition to its ability to support bone formation and prevent infection make this cryogel an attractive candidate for bone tissue engineering applications.

Synthesis and Evaluation of a Zinc Eluting rGO/Hydroxyapatite Nanocomposite Optimized for Bone Augmentation.

Repair of critical size bone defects is a clinical challenge that usually necessitates the use of bone substitutes. For successful bone repair, the substitute should possess osteoconductive, osteoinductive, and vascularization potential, with the ability to control post-implantation infection serving as an additional advantage. With an aim to develop one such substitute, we optimized a zinc-doped hydroxyapatite (HapZ) nanocomposite decorated on reduced graphene oxide (rGO), termed as G3HapZ, and demonstrated its potential to augment the bone repair. The biocompatible composite displayed its osteoconductive potential in biomineralization studies, and its osteoinductive property was confirmed by its ability to induce mesenchymal stem cell (MSC) differentiation to osteogenic lineage assessed by in vitro mineralization (Alizarin red staining) and expression of osteogenic markers including runt-related transcription factor 2 (RUNX-2), alkaline phosphatase (ALP), type 1 collagen (COL1), bone morphogenic protein-2 (BMP-2), osteocalcin (OCN), and osteopontin (OPN). While the potential of G3HapZ to support vascularization was displayed by its ability to induce endothelial cell migration, attachment, and proliferation, its antimicrobial activity was confirmed using S. aureus. Biocompatibility of G3HapZ was demonstrated by its ability to induce bone regeneration and neovascularization in vivo. These results suggest that G3HapZ nanocomposites can be exploited for a range of strategies in developing orthopedic bone grafts to accelerate bone regeneration.