Restoring disc matrix homeostasis: Dual-miRNA and human platelet lysate as a novel therapeutic strategy Tara Ní Néill, Niamh Wilson, Jijo Thomas, Jake McDonnell, Stacey L. Darwish, Joseph S. Butler, Fergal J. O'Brien, James E. Dixon, Caroline M. Curtin, Conor T. Buckley Materials Today Bio, 2026 Intervertebral disc (IVD) degeneration is the predominant cause of low back pain, resulting from progressive extracellular matrix (ECM) degradation and establishment of a pro-catabolic microenvironment. microRNA (miRNA) delivery has potential to promote ECM restoration and curb the catabolic milieu. We previously demonstrated a robust anti-catabolic effect through the delivery of a dual-miRNA injectable therapy in ex vivo organ culture models of degeneration. However, to further enhance regenerative outcomes, additional stimulation, such as supplementation with human platelet lysate (HPL) may strengthen this therapeutic strategy. Supplementation of rat nucleus pulposus (NP) cells with the dual-miRNA-FLR-149-5p mimic and miRNA-221-3p inhibitor and HPL was assessed in monolayer and ex vivo organ culture modelling mild degeneration. To evaluate the translatability of our approach, a tuneable patient NP cell-laden NP-ECM gel analogue was developed. For all models, key ECM constituents and matrix-degrading proteins were assessed biochemically, histologically, and using immunofluorescence. HPL supplementation combined with FLR-miRNA-149-5p and 221-3p inhibitor resulted in increased ECM regenerative proteins, SRY-box transcription factor 9 (SOX9), and aggrecan, while suppressing catabolic factors from matrix-degrading enzymes disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinases (MMPs). Importantly, rat and human culture models were consistent in their response, highlighting the clinical translatability of our models and therapeutic strategy. Combined delivery of dual-miRNA with HPL delivery in rat and human models of mild degeneration enhanced expression of restorative ECM proteins while suppressing matrix-degrading factors. These findings highlight a novel and promising therapeutic strategy for the treatment of early-stage IVD degeneration.
Post-Implantation Stiffening by a Bioinspired, Double-Network, Self-Healing Hydrogel Facilitates Minimally Invasive Cell Delivery for Cartilage Regeneration Jijo Thomas, Vianni Chopra, Swati Rajput, Rajdeep Guha, Naibedya Chattopadhyay, Deepa Ghosh Biomacromolecules, 2023 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 Vianni Chopra, Jijo Thomas, Swati Kaushik, Swati Rajput, Rajdeep Guha, Bidya Mondal, Sudip Naskar, Dipankar Mandal, Gaurav Chauhan, Naibedya Chattopadhyay, Deepa Ghosh Small, 2023 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.
Gelatin Nanofibers Loaded with Zinc-Doped Hydroxyapatite for Osteogenic Differentiation of Mesenchymal Stem Cells Vianni Chopra, Jijo Thomas, Gaurav Chauhan, Swati Kaushik, Swati Rajput, Rajdeep Guha, Naibedya Chattopadhyay, Sergio O. Martinez-Chapa, Deepa Ghosh ACS Applied Nano Materials, 2022 Tissue engineering of bones often necessitates the addition of exogenous growth factors and supplements to accelerate the differentiation of mesenchymal stem cells to osteogenic lineage, thereby increasing its cost. On the postulation that a scaffold that mimics the micro-/nano-bone architecture per se can provide the essential cues to favor osteogenesis, we developed gelatin nanofibers and loaded them with zinc-doped nano-hydroxyapatite (ZnHp). To further improve its osteogenic potential, the above nano-composite was additionally decorated with rGO platelets (ZnHp@rGO) and incorporated in gelatin nanofibers. On in vitro evaluation, the respective gelatin nanofibers appeared to aid the accelerated differentiation of mesenchymal stem cells toward the osteogenic lineage without the need for any exogenous osteogenic supplement in the milieu. The biomimetic cues provided by ZnHp and ZnHp@rGO also favored angiogenesis, with enhanced CD-31 and iNOS expression. The ability of these nanofibers to induce vascularization was confirmed using an in ovo and in vivo rat model. Apart from its osteoinductive and angiogenic properties, the nanofibers exhibited favorable anti-biofilm activity by preventing the growth of Staphylococcus aureus. Although these results suggest the potential of the scaffold for inducing bone repair in vivo, it also confirms that bones can be engineered at a relatively low cost by designing scaffolds having topographical and biochemical cues that mimic the bone microarchitecture.
A drug-free strategy to combat bacterial infections with magnetic nanoparticles biosynthesized in bacterial pathogens Swati Kaushik, Jijo Thomas, Vineeta Panwar, Preethi Murugesan, Vianni Chopra, Navita Salaria, Rupali Singh, Himadri Shekar Roy, Rajesh Kumar, Vikas Gautam, Deepa Ghosh Nanoscale, 2022 Pathogenic bacteria, both in vitro and in the host biosynthesize intracellular magnetic nanoparticles. The magnet-responsive pathogens can be destroyed using an alternating magnetic field.
Mechanical Integrity in a Dynamic Interpenetrating Hydrogel Network of Supramolecular Peptide-Polysaccharide Supports Enhanced Chondrogenesis Jijo Thomas, Nidhi Gupta, Jojo P. Joseph, Vianni Chopra, Asish Pal, Deepa Ghosh ACS Biomaterials Science and Engineering, 2021 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 Jijo Thomas, Vianni Chopra, Anjana Sharma, Vineeta Panwar, Swati Kaushik, Swati Rajput, Monika Mittal, Rajdeep Guha, Naibedya Chattopadhyay, Deepa Ghosh International Journal of Biological Macromolecules, 2021 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 Vineeta Panwar, Anand Babu, Anjana Sharma, Jijo Thomas, Vianni Chopra, Pinki Malik, Swati Rajput, Monika Mittal, Rajdeep Guha, Naibedya Chattopadhyay, Dipankar Mandal, Deepa Ghosh Journal of Materials Chemistry B, 2021 Conductive hydrogels are attracting considerable interest in view of their potential in a wide range of applications that include healthcare and electronics.
Actin-binding carbon dots selectively target glioblastoma cells while sparing normal cells Anjana Sharma, Vineeta Panwar, Jijo Thomas, Vianni Chopra, Himadri Shekhar Roy, Deepa Ghosh Colloids and Surfaces B Biointerfaces, 2021 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.
Restoring disc matrix homeostasis: Dual-miRNA and human platelet lysate as a novel therapeutic strategy TN Néill, N Wilson, J Thomas, J McDonnell, SL Darwish, JS Butler, ... Materials Today Bio 38, 103190 , 2026 2026
Post-implantation stiffening by a bioinspired, double-network, self-healing hydrogel facilitates minimally invasive cell delivery for cartilage regeneration J Thomas, V Chopra, S Rajput, R Guha, N Chattopadhyay, D Ghosh Biomacromolecules 24 (7), 3313-3326 , 2023 2023 Citations: 15
Injectable bone cement reinforced with gold nanodots decorated rGO‐hydroxyapatite nanocomposites, augment bone regeneration V Chopra, J Thomas, S Kaushik, S Rajput, R Guha, B Mondal, S Naskar, ... Small 19 (14), 2204637 , 2023 2023 Citations: 35
Electrical stimulation induced by a piezo-driven triboelectric nanogenerator and electroactive hydrogel composite, accelerate wound repair A Sharma, V Panwar, B Mondal, D Prasher, MK Bera, J Thomas, A Kumar, ... Nano Energy 99, 107419 , 2022 2022 Citations: 124
Gelatin nanofibers loaded with zinc-doped hydroxyapatite for osteogenic differentiation of mesenchymal stem cells V Chopra, J Thomas, G Chauhan, S Kaushik, S Rajput, R Guha, ... ACS Applied Nano Materials 5 (2), 2414-2428 , 2022 2022 Citations: 21
Injectable Self-Healing Hydrogels for Cartilage Tissue Engineering J Thomas IISER Mohali , 2022 2022
A Drug-free Strategy to Combat Bacterial Infections with Magnetic Nanoparticles Biosynthesized in the Bacterial Pathogens S Kaushik, J Thomas, V Panwar, P Murugesan, V Chopra, N Salaria, ... Nanoscale , 2022 2022 Citations: 16
Mechanical integrity in a dynamic interpenetrating hydrogel network of supramolecular peptide–polysaccharide supports enhanced chondrogenesis J Thomas, N Gupta, JP Joseph, V Chopra, A Pal, D Ghosh ACS Biomaterials Science & Engineering 7 (12), 5798-5809 , 2021 2021 Citations: 38
An injectable hydrogel having proteoglycan-like hierarchical structure supports chondrocytes delivery and chondrogenesis J Thomas, V Chopra, A Sharma, V Panwar, S Kaushik, S Rajput, M Mittal, ... International journal of biological macromolecules 190, 474-486 , 2021 2021 Citations: 25
A bioinspired, ice-templated multifunctional 3D cryogel composite crosslinked through in situ reduction of GO displayed improved mechanical, osteogenic and antimicrobial properties V Chopra, J Thomas, A Sharma, V Panwar, S Kaushik, D Ghosh Materials Science and Engineering: C 119, 111584 , 2021 2021 Citations: 30
Tunable, conductive, self-healing, adhesive and injectable hydrogels for bioelectronics and tissue regeneration applications V Panwar, A Babu, A Sharma, J Thomas, V Chopra, P Malik, S Rajput, ... Journal of Materials Chemistry B 9 (31), 6260-6270 , 2021 2021 Citations: 50
Actin-binding Carbon dots selectively target glioblastoma cells while sparing normal cells A Sharma, V Panwar, J Thomas, V Chopra, HS Roy, D Ghosh Colloids and Surfaces B: Biointerfaces, 111572 , 2021 2021 Citations: 30
Synthesis and evaluation of a zinc eluting rGO/hydroxyapatite nanocomposite optimized for bone augmentation V Chopra, J Thomas, A Sharma, V Panwar, S Kaushik, S Sharma, ... ACS Biomaterials Science & Engineering 6 (12), 6710-6725 , 2020 2020 Citations: 47
In-vitro and in-vivo evaluation of modified sodium starch glycolate for exploring its haemostatic potential V Panwar, J Thomas, A Sharma, V Chopra, S Kaushik, A Kumar, D Ghosh Carbohydrate polymers 235, 115975 , 2020 2020 Citations: 13
In situ biosynthesized superparamagnetic iron oxide nanoparticles (SPIONS) induce efficient hyperthermia in cancer cells S Kaushik, J Thomas, V Panwar, H Ali, V Chopra, A Sharma, R Tomar, ... ACS Applied Bio Materials 3 (2), 779-788 , 2020 2020 Citations: 56
In-vitro and In-vivo evaluation of biocompatible and biodegradable calcium-modified carboxymethyl starch as a topical hemostat V Panwar, A Sharma, J Thomas, V Chopra, S Kaushik, A Kumar, D Ghosh Materialia 7, 100373 , 2019 2019 Citations: 29
Interaction of carbon dots with endothelial cells: implications for biomedical applications A Sharma, V Panwar, V Chopra, J Thomas, S Kaushik, D Ghosh ACS Applied Nano Materials 2 (9), 5483-5491 , 2019 2019 Citations: 34
Polysaccharide-based hybrid self-healing hydrogel supports the paracrine response of mesenchymal stem cells J Thomas, A Sharma, V Panwar, V Chopra, D Ghosh ACS Applied Bio Materials 2 (5), 2013-2027 , 2019 2019 Citations: 51
MOST CITED SCHOLAR PUBLICATIONS
Electrical stimulation induced by a piezo-driven triboelectric nanogenerator and electroactive hydrogel composite, accelerate wound repair A Sharma, V Panwar, B Mondal, D Prasher, MK Bera, J Thomas, A Kumar, ... Nano Energy 99, 107419 , 2022 2022 Citations: 124
In situ biosynthesized superparamagnetic iron oxide nanoparticles (SPIONS) induce efficient hyperthermia in cancer cells S Kaushik, J Thomas, V Panwar, H Ali, V Chopra, A Sharma, R Tomar, ... ACS Applied Bio Materials 3 (2), 779-788 , 2020 2020 Citations: 56
Polysaccharide-based hybrid self-healing hydrogel supports the paracrine response of mesenchymal stem cells J Thomas, A Sharma, V Panwar, V Chopra, D Ghosh ACS Applied Bio Materials 2 (5), 2013-2027 , 2019 2019 Citations: 51
Tunable, conductive, self-healing, adhesive and injectable hydrogels for bioelectronics and tissue regeneration applications V Panwar, A Babu, A Sharma, J Thomas, V Chopra, P Malik, S Rajput, ... Journal of Materials Chemistry B 9 (31), 6260-6270 , 2021 2021 Citations: 50
Synthesis and evaluation of a zinc eluting rGO/hydroxyapatite nanocomposite optimized for bone augmentation V Chopra, J Thomas, A Sharma, V Panwar, S Kaushik, S Sharma, ... ACS Biomaterials Science & Engineering 6 (12), 6710-6725 , 2020 2020 Citations: 47
Mechanical integrity in a dynamic interpenetrating hydrogel network of supramolecular peptide–polysaccharide supports enhanced chondrogenesis J Thomas, N Gupta, JP Joseph, V Chopra, A Pal, D Ghosh ACS Biomaterials Science & Engineering 7 (12), 5798-5809 , 2021 2021 Citations: 38
Injectable bone cement reinforced with gold nanodots decorated rGO‐hydroxyapatite nanocomposites, augment bone regeneration V Chopra, J Thomas, S Kaushik, S Rajput, R Guha, B Mondal, S Naskar, ... Small 19 (14), 2204637 , 2023 2023 Citations: 35
Interaction of carbon dots with endothelial cells: implications for biomedical applications A Sharma, V Panwar, V Chopra, J Thomas, S Kaushik, D Ghosh ACS Applied Nano Materials 2 (9), 5483-5491 , 2019 2019 Citations: 34
A bioinspired, ice-templated multifunctional 3D cryogel composite crosslinked through in situ reduction of GO displayed improved mechanical, osteogenic and antimicrobial properties V Chopra, J Thomas, A Sharma, V Panwar, S Kaushik, D Ghosh Materials Science and Engineering: C 119, 111584 , 2021 2021 Citations: 30
Actin-binding Carbon dots selectively target glioblastoma cells while sparing normal cells A Sharma, V Panwar, J Thomas, V Chopra, HS Roy, D Ghosh Colloids and Surfaces B: Biointerfaces, 111572 , 2021 2021 Citations: 30
In-vitro and In-vivo evaluation of biocompatible and biodegradable calcium-modified carboxymethyl starch as a topical hemostat V Panwar, A Sharma, J Thomas, V Chopra, S Kaushik, A Kumar, D Ghosh Materialia 7, 100373 , 2019 2019 Citations: 29
An injectable hydrogel having proteoglycan-like hierarchical structure supports chondrocytes delivery and chondrogenesis J Thomas, V Chopra, A Sharma, V Panwar, S Kaushik, S Rajput, M Mittal, ... International journal of biological macromolecules 190, 474-486 , 2021 2021 Citations: 25
Gelatin nanofibers loaded with zinc-doped hydroxyapatite for osteogenic differentiation of mesenchymal stem cells V Chopra, J Thomas, G Chauhan, S Kaushik, S Rajput, R Guha, ... ACS Applied Nano Materials 5 (2), 2414-2428 , 2022 2022 Citations: 21
A Drug-free Strategy to Combat Bacterial Infections with Magnetic Nanoparticles Biosynthesized in the Bacterial Pathogens S Kaushik, J Thomas, V Panwar, P Murugesan, V Chopra, N Salaria, ... Nanoscale , 2022 2022 Citations: 16
Post-implantation stiffening by a bioinspired, double-network, self-healing hydrogel facilitates minimally invasive cell delivery for cartilage regeneration J Thomas, V Chopra, S Rajput, R Guha, N Chattopadhyay, D Ghosh Biomacromolecules 24 (7), 3313-3326 , 2023 2023 Citations: 15
In-vitro and in-vivo evaluation of modified sodium starch glycolate for exploring its haemostatic potential V Panwar, J Thomas, A Sharma, V Chopra, S Kaushik, A Kumar, D Ghosh Carbohydrate polymers 235, 115975 , 2020 2020 Citations: 13
Restoring disc matrix homeostasis: Dual-miRNA and human platelet lysate as a novel therapeutic strategy TN Néill, N Wilson, J Thomas, J McDonnell, SL Darwish, JS Butler, ... Materials Today Bio 38, 103190 , 2026 2026
Injectable Self-Healing Hydrogels for Cartilage Tissue Engineering J Thomas IISER Mohali , 2022 2022
