Rajendra Kumar Singh

Chronic diabetic wounds present a critical clinical challenge due to persistent inflammation and compromised healing. Here, we report a sprayable nanozyme hydrogel that epigenetically remodels macrophages (Mφ) to suppress inflammation and coordinate regeneration. Ultrasmall copper-based nanozymes (CuNZ, ~4 nm) synthesized via an eco-friendly one-pot method demonstrated potent multi-radical scavenging activity. When integrated into gelatin methacryloyl (Gel), CuNZ@Gel exhibited sprayability, conformal skin coverage, and storage stability, offering potential for clinical translation. Notably, the nanozyme hydrogel induced distinct epigenetic modifications in Mφ by remodeling chromatin accessibility, thereby shifting gene expression from a pro-inflammatory to an anti-inflammatory profile. This epigenetic modulation sustained under oxidative stress, actively suppressing inflammation while facilitating regenerative responses. In rat diabetic wound models, CuNZ@Gel significantly accelerated healing through its coordinated antioxidant, anti-inflammatory, and pro-regenerative actions. Unlike conventional passive dressings, this sprayable nanozyme hydrogel proactively remodels the wound microenvironment via epigenetic control of inflammation, providing a promising therapeutic strategy for managing chronic diabetic wounds and inflammatory skin complications.

Bioprinting is reshaping the field of tissue regeneration and drug screening by creating physiologically accurate and scalable tissue models that reduce the limitations of conventional animal testing. It helps to minimize interspecies variability by developing complex 3D tissue structures that closely mimic the structural and functional characteristics of native tissues, ensuring high reproducibility. Furthermore, it supports more humane and sustainable preclinical testing by aligning with the ethical 3Rs principles (Replacement, Reduction and Refinement). Although bioprinting offers many advantages, its full potential in evaluating drug testing applications has yet to be harnessed. In this review, we discuss the efficacy of key bioprinting techniques in replicating the structural and functional characteristics of engineered tissues, comparing them with their native counterparts. Further, we highlight case studies demonstrating the applications of bioprinted skin, cardiac, hepatic, renal, bone, and cancer models in pharmaceutical research. The commercialization of bioprinted drug testing platforms and their integration into pharmaceutical development are also discussed. Finally, we outline key advantages, current challenges, and future directions needed to establish bioprinting as a transformative tool for preclinical drug testing, aiming to replace traditional animal models.

Treating chronic bone injuries and defects remains a significant challenge in orthopedic medicine, impacting patient mobility, recovery time, and healthcare costs. The periosteum, a specialized, vascularized connective tissue covering the outer bone surface, plays a crucial role in osteogenesis and skeletal repair. While regenerating the periosteum is critical to restoring bone structure and function, current treatments face substantial limitations, including limited donor tissue availability, donor site complications, and the risk of immunological rejection. Recent advances in biomaterial engineering have driven the development of therapeutic platforms specifically designed to promote periosteal regeneration. These biomaterial-based platforms mimic the biochemical and biomechanical properties of the native periosteal microenvironment. By facilitating key cellular processes involved in osteogenesis and angiogenesis, these materials enable controlled spatiotemporal delivery of bioactive molecules, ion release, modulation of reactive oxygen species (ROS), and enhancement of pro-angiogenic factors. In this review, we discuss the recent advancements in engineered biomaterials, focusing on their mechanisms of action and applications in periosteum restoration. We also provide insights into current challenges and future research directions, emphasizing the critical role of these strategies in clinical practice. The perspectives offered here aim to guide the development of targeted, effective therapies for periosteum repair, ultimately advancing functional bone regeneration.

Osteoarthritis involves complex inflammatory responses, leading to cell death and joint dysfunction. Key contributors are pro-inflammatory molecules, such as excess reactive oxygen species (ROS) and cell-free DNA (cfDNA), which require effective scavenging. Concurrently, delivering anti-inflammatory agents can stimulate immune cells to restore tissue repair by resolving inflammation. Thus, a "push-and-pull" approach-combining delivery and scavenging-is optimal for osteoarthritis treatment. Here, we propose a multitherapeutic strategy using polycationic-functionalized mesoporous ceria nanoparticle (mCNP-G) to target osteoarthritic joint cartilage. The mCNP core, with its multiple catalytic capabilities and mesoporous structure, was effective in scavenging ROS and loading/releasing the anti-inflammatory drug dexamethasone. Additionally, polycationic functionalization enhanced the scavenging of cfDNA released from damaged or dying cells. These combined functions of mCNP-G substantially down-regulated pro-inflammatory signaling, thereby rescuing cells and interrupting the inflammatory feedback loop. Moreover, mCNP-G demonstrated high affinity for cartilage tissue, facilitating targeted retention to osteoarthritis region. When locally administered to rat osteoarthritic temporomandibular joint, mCNP-G with dexamethasone significantly reduced cfDNA and oxidative stress, inhibited inflammation, and salvaged cells, ultimately alleviating osteoarthritic symptoms and osteochondral damage. This nanomedicine offers a promising therapeutic strategy for osteoarthritis by integrating the push-and-pull functions of drug delivery and ROS/cfDNA dual-scavenging within a single system.

Skin injuries and wounds present significant clinical challenges, necessitating the development of advanced wound dressings for efficient wound healing and tissue regeneration. In this context, the advancement of hydrogels capable of counteracting the adverse effects arising from undesirable reactive oxygen species (ROS) is of significant importance. This study introduces a hybrid hydrogel with rapid photocuring and excellent conformability, tailored to ameliorate the hostile microenvironment of damaged skin tissues. The hybrid hydrogel, composed of photoresponsive Gelatin Methacryloyl (GelMA) and Molybdenum-based nanoclusters (MNC), exhibits physicochemical characteristics conductive to skin regeneration. In vitro studies demonstrated the cytocompatibility and ROS-responsive behavior of the MNC/GelMA hybrid hydrogels, confirming their ability to promote human dermal fibroblasts (HDF) functions. The incorporation of MNC into GelMA not only enhances HDF adhesion, proliferation, and migration but also shields against oxidative damage induced by hydrogen peroxide (H₂O₂). Notably, in vivo evaluation in murine full-thickness skin defects revealed that the application of hybrid hydrogel dressings led to reduced inflammation, accelerated wound closure, and enhanced collagen deposition in comparison to control groups. Significantly, this study introduced a convenient approach to develop in situ ROS-scavenging hydrogel dressings to accelerate the wound healing process without the need for exogenous cytokines or medications. We consider that the nanoengineering approach proposed herein offers potential possibilities for the development of therapeutic hydrogel dressings addressing various skin-related conditions.

Magnetite (Fe₃O₄) nanoparticle (MNP)-substituted glass-ceramic (MSGC) powders with compositions of (45 − x)SiO₂–24.5CaO–24.5Na₂O–6P₂O₅–xFe₃O₄ (x = 5, 8, and 10 wt%) have been prepared by a sol–gel route by introducing MNP during the synthesis.

The design of implantable biomaterials involves precise tuning of surface features because the early cellular fate on such engineered surfaces is highly influenced by many physicochemical factors [roughness, hydrophilicity, reactive oxygen species (ROS) responsiveness, etc.]. Herein, to enhance soft tissue integration for successful implantation, Ti substrates decorated with uniform layers of nanoceria (Ce), called Ti@Ce, were optimally developed by a simple and cost-effective in situ immersion coating technique. The characterization of Ti@Ce shows a uniform Ce distribution with enhanced roughness (∼3-fold increase) and hydrophilicity (∼4-fold increase) and adopted ROS-scavenging capacity by nanoceria coating. When human gingival fibroblasts were seeded on Ti@Ce under oxidative stress conditions, Ti@Ce supported cellular adhesion, spreading, and survivability by its cellular ROS-scavenging capacity. Mechanistically, the unique nanocoating resulted in higher expression of amphiphysin (a nanotopology sensor), paxillin (a focal adhesion protein), and cell adhesive proteins (collagen-1 and fibronectin). Ti@Ce also led to global chromatin condensation by decreasing histone 3 acetylation as an early differentiation feature. Transcriptome analysis by RNA sequencing confirmed the chromatin remodeling, antiapoptosis, antioxidant, cell adhesion, and TGF-β signaling-related gene signatures in Ti@Ce. As key fibroblast transcription (co)factors, Ti@Ce promotes serum response factor and MRTF-α nucleus localization. Considering all of this, it is proposed that the surface engineering approach using Ce could improve the biological properties of Ti implants, supporting their functioning at soft tissue interfaces and utilization as a bioactive implant for clinical conditions such as peri-implantitis.

Poly(methyl methacrylate) (PMMA) is commonly used for dental dentures, but it has the drawback of promoting oral health risks due to oral bacterial adhesion. Recently, various nanoparticles have been incorporated into PMMA to tackle these issues. This study aims to investigate the mechanophysical and antimicrobial adhesive properties of a denture resin by incorporating of nanoclay into PMMA. Specimens were prepared by adding 0, 1, 2, and 4 wt % surface-modified nanoclay (Sigma) to self-polymerizing PMMA denture resin. These specimens were then evaluated using FTIR, TGA/DTG, and FE-SEM with EDS. Various mechanical and surface physical properties, including nanoindentation, were measured and compared with those of pure PMMA. Antiadhesion experiments were conducted by applying a Candida albicans (ATCC 11006) suspension to the surface of the specimens. The antiadhesion activity of C. albicans was confirmed through a yeast-wall component (mannan) and mRNA-seq analysis. The bulk mechanical properties of nanoclay-PMMA composites were decreased compared to those of pure PMMA, while the flexural strength and modulus met the ISO 20795-1 requirement. However, there were no significant differences in the nanoindentation hardness and elastic modulus. The surface energy revealed a significant decrease at 4 wt % nanoclay-PMMA. The antiadhesion effect of Candida albicans was evident along with nanoclay content in the nanocomposites and confirmed by the reduced attachment of mannan on nanoclay-PMMA composites. mRNA-seq analysis supported overall transcriptome changes in altering attachment and metabolism behaviors on the surface. The nanoclay-PMMA materials showed a lower surface energy as the content increased, leading to an antiadhesion effect against Candida albicans. These findings indicate that incorporating nanoclay into PMMA surfaces could be a valuable strategy for preventing the fungal biofilm formation of denture base materials.

The dura mater, as the crucial outermost protective layer of the meninges, plays a vital role in safeguarding the underlying brain tissue. Neurosurgeons face significant challenges in dealing with trauma or large defects in the dura mater, as they must address the potential complications, such as wound infections, pseudomeningocele formation, cerebrospinal fluid leakage, and cerebral herniation. Therefore, the development of dural substitutes for repairing or reconstructing the damaged dura mater holds clinical significance. In this review we highlight the progress in the development of dural substitutes, encompassing autologous, allogeneic, and xenogeneic replacements, as well as the polymeric-based dural substitutes fabricated through various scaffolding techniques. In particular, we explore the development of composite materials that exhibit improved physical and biological properties for advanced dural substitutes. Furthermore, we address the challenges and prospects associated with developing clinically relevant alternatives to the dura mater.