Diabetic wound healing presents a major challenge due to impaired vascular function, chronic inflammation, and a defective immune response caused by hyperglycemia. Current wound care technologies, including hydrogels, growth factor therapies, and bioengineered skin substitutes, have inherent limitations and fail to address the complex healing requirements of diabetic wounds. In this study, we report the development of a silk fibroin-based scaffold that exhibits controlled drug delivery modulated by the presence of bioinspired surface patterns. We demonstrate remarkable in vivo efficacy of the patterned scaffold in a diabetic rat model. Wound healing and tissue regeneration were tracked using Swept-Source Optical Coherence Tomography (SS-OCT), histopathology, and molecular analysis (immunohistochemistry and quantitative PCR). We show that the scaffold significantly accelerates wound healing, as evidenced by enhanced cellular differentiation, angiogenesis, and extracellular matrix remodeling. These findings highlight the scaffold's ability to overcome the limitations of current wound care technologies by integrating structural support with sustained drug release. The approach not only improves wound closure and tissue regeneration but also provides a promising, bioinspired solution for targeted diabetic wound management with high potential for clinical translation.

Surface functionalization strategies to replicate extracellular matrix (ECM) properties often rely on chemical modification. However, issues such as cytotoxicity, poor degradation control, and sensitivity to physiological conditions limit their applicability in long-term and translational contexts. To address this, we report a material-independent, chemically inert approach that uses biomimetic surface topographies to direct cell behavior using physical cues alone. While natural surfaces offer a wealth of hierarchical micro/nano architectures, the functional distinctions among topographies derived from different phenotypes of the same biological origin remain underexplored. Here, we present a systematic comparison of polydimethylsiloxane (PDMS) replicas inspired by lotus leaves, red rose petals, and yellow rose petals to examine their influence on fibroblast behavior. Using soft lithography and UV-assisted replication, we fabricate high-fidelity surfaces and characterize them via atomic force microscopy (AFM) and scanning electron microscopy (SEM). Cellular responses were assessed through proliferation assays, morphological analysis, fluorescence imaging, and mechanosensing behavior. Our results reveal that each surface elicits distinct cell-substrate interaction profiles, with the yellow rose petal-inspired topography showing superior support for adhesion, spreading, and proliferation. This behavior is attributed to its unique topographical density and orientation. The study offers a novel framework for harnessing natural geometries in the design of reproducible and cytocompatible platforms for regenerative and in vitro biomedical applications.

Rose petals exhibit a phenomenal wetting property of being sticky and superhydrophobic simultaneously. A recent study has shown that for short timescales, associated with drop impact phenomenon, lotus leaf and rose petal replicas exhibit similar wettability, thereby highlighting the difference between long and short time wettability. Also, short time wetting on rose petals of different colors remains completely unaddressed, as almost all existing study on wetting of rose petals have been performed with the classical red rose (Rosa chinensis). In this paper, we compare the drop impact studies on replicas of a yellow rose petal, with those on extensively studied red rose petal replicas and the lotus leaf over a wide range of Weber number (We), by varying the height of fall (h) from 10 to 375 mm. Our results reveal that over the replica of a yellow rose petal, the initial impact outcome varies from complete rebound to micro pinning and eventually complete pinning depending on the kinetic energy of the impacting drop, in contrast to that on red rose petal replica on which the droplet always pinned. Based on experimental finding, we present a comprehensive regime phase map of the post impact behavior of the drop on different surfaces as a function of impact height. We also present a simple scaling analysis to understand the combined effect of pattern height and periodicity on the critical h corresponding to wetting regime transition. Additionally, variation of maximum spreading diameter and spreading time with the h for the different surfaces is also discussed. The results highlight that the initial impact dynamics of a water drop over a topographically patterned substrate is a strong function of the topographical parameters and can be very different from the equilibrium wetting state.

While a sticking plasteris enough for healing of most of the minor cuts they may get routinely, critical situations like surgical, gunshot, accidental or diabetic wounds;lacarations and other cutaneous deep cuts may require implants and simultaneous medications for healing. From the biophysical standpoint, an internal force-based physical surface stimulusis crucial for cellular sensing during wound repair. In this paper, the authors report the fabrication of a porous, biomimmetically patterned silk fibroin scaffold loaded with ampicillin, which exhibits controlled release of the drug along with possible replenishment of the same. In vitro swelling study reveals that the scaffolds with hierarchical surface patterns exhibit lower swelling and degradation than other types of scaffolds. The scaffolds, that show remarkable broad-spectrum antibacterial efficacy, exhibit Korsemeyer-Peppas model for the ampicillin release patterns due to the structural hydrophobicity imparted by the patterns. Four distinct cell-matrix adhesion regimes are investigated for the fibroblasts to eventually form cell sheets all over the hierarchical surface structures. 4',6-diamidino-2-phenylindole (DAPI) and Fluorescein Diacetate (FDA) fluorescent staining clearly demonstrate the superiority of patterned surface over its other variants. A comparative immunofluorescence study among collagen I, vinculin, and vimentin expressions substantiated the patterned surface to be superior to others.

We report synergism in scarless cutaneous wound repair by alginate hydrogel (HGSAG) embedded with an optimized blend of characterized Jamun honey and characterized indigenously prepared ghee. Thorough screening and characterization of honey and ghee are carried out followed by obtaining a novel dual crosslinking percolative gel casting fabrication method to come up with HGSAG showing superior chemical stability, and mechanical strength (Nanoindentation study; lowest stiffness: 0.71 ± 0.19 μN/nm), and surface morphology (SEM; highest roughness: 0.13 ± 0.04 μm) to other variants. In vitro swelling study and degradation behavior study show intermediate swelling (swelling index: 0.59 ± 0.008 in 98 h) and required restricted degradation (PBS: 73.38 ± 0.55%, DMEM: 83.48 ± 0.69% in 10 days) for HGSAG which is necessary for providing nutrients to cells and in vivo therapeutic efficacy. We observe the remarkable antibacterial efficacy of HGSAG against Staphylococcus mutans and Escherichia coli. This particular substrate also shows decent 3T3 fibroblasts viability, cell-cell communication followed by cell-matrix interaction, and proliferation compared to other variants. Molecular gene expression studies by quantitative RT-PCR technique reveal strong upregulation of collagen I, CD26, and TGF-β3 while downregulation in the case of TGF-β1 which eventually substantiates scarless wound healing potential of HGSAG. Wound closure kinetics is most rapidly and successfully underpinned by HGSAG while compared to other alternatives including marketed healing patches. Regular close monitoring using histopathological studies and real-time imaging by Swept-Source Optical Coherence Tomography of in vivo wound model treated with HGSAG come up with the fascinating result of scarless healing (HGSAG treated epithelial thickness: 62.96 ± 0.67 μm, unwounded akin epithelial thickness: 62.56 ± 0.34 μm) within 12 days of wounding. Thus, the work highlights modified and stabilized alginate hydrogel embedded with honey and ghee blend as a potential scarless full-thickness cutaneous wound healing bio-scaffold.

The incorrect metabolic breakdown of the nonaromatic amino acid methionine (Met) leads to the disorder called hypermethioninemia via an unknown mechanism. To understand the molecular level pathogenesis of this disorder, we prepared a DMPC lipid membrane, the mimicking setup of the cell membrane, and explored the effect of the millimolar level of Met on it. We found that Met forms toxic fibrillar aggregates that disrupt the rigidity of the membrane bilayer, and increases the dynamic response of water molecules surrounding the membrane as well as the heterogeneity of the membrane. Such aggregates strongly deform red blood cells. This opens the requirement to consider therapeutic antagonists either to resist or to inhibit the toxic amyloid aggregates against hypermethioninemia. Moreover, such disrupting effect on membrane bilayer and cytotoxicity along with deformation effect on RBC by the cross amyloids of Met and Phenylalanine (Phe) was found to be most virulent. This exclusive observation of the enhanced virulent effect of the cross amyloids is expected to be an informative asset to explain the coexistence of two amyloid disorders.

Clinical success of regenerative medicine for treating deep-tissue skin injuries depends on the availability of skin grafts. Though bioengineered constructs are tested clinically, lack of neovascularization provide only superficial healing. Thus constructs, which promotes wound healing and supports vascularization has gained priority in tissue engineering. In this study, chitosan-collagen-fibrinogen (CCF) scaffold was fabricated using freeze-drying method without using any chemical crosslinkers. CCF scaffolds proved cytocompatibility and faster healing in in vitro scratch assay of primary human adult dermal fibroblasts cells with progressively increasing vascular endothelial growth factor-A and reducing vascular endothelial growth factor receptor 1 expressions. Skin regeneration evaluated on in vivo full thickness wound model confirmed faster remodeling with angiogenic signatures in CCF scaffold-implanted mice. Histopathological observations corroborated with stereo-zoom and SS-optical coherence tomography images of wound sites to prove the maturation of healing-bed, after 12 days of CCF implantation. Therefore, it is concluded that CCF scaffolds are promising for skin tissue regeneration and demonstrates pro-angiogenic potential.

We report a significant improvement of adipose-derived mesenchymal stem cells' (ADMSCs) biocompatibility and proliferation on hierarchically patterned porous honey-incorporated silk fibroin scaffolds fabricated using a combination of soft lithography and freeze-drying techniques. Parametric variations show enhanced surface roughness, swelling, and degradation rate with good pore interconnectivity, porosity, and mechanical strength for soft-lithographically fabricated biomimetic microdome arrays on the 2% honey silk fibroin scaffold (PHSF2) as compared to its other variants, which eventually made PHSF2 more comparable to the native environment required for stem cell adhesion and proliferation. PHSF2 also exhibits sustained honey release with remarkable antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA). Honey incorporation (biochemical cue) influences microdome structural features, that is, biophysical cues (height, width, and periodicity), which further allows ADMSCs pseudopods (filopodia) to grasp the microdomes for efficient cell-cell communication and cell-matrix interaction and regulates ADMSCs behavior by altering their cytoskeletal rearrangement and thereby increases the cellular spreading area and cell sheet formation. The synergistic effect of biochemical (honey) and biophysical (patterns) cues on ADMSCs studied by the nitro blue tetrazolium assay and DCFDA fluorescence spectroscopy reveals limited free radical generation within cells. Molecular expression studies show a decrease in p53 and p21 expressions validating ADMSCs senescence inhibition, which is further correlated with a decrease in cellular senescence-associated β galactosidase activity. We also show that an increase in CDH1 and CK19 molecular expressions along with an increase in SOX9, RUNX2, and PPARγ molecular expressions supported by PHSF2 justify the substrate's efficacy of underpinning mesenchymal to epithelial transition and multilineage trans-differentiation. This work highlights the fabrication of a naturally healing nutraceutical (honey)-embedded patterned porous stand-alone tool with the potential to be used as smart stem cells delivering regenerative healing implant.

Dermal reconstruction in acute and chronic wounds needs highly vascularized dermal tissue engineered skin substitutes which has the potentiality to provide physical cues as well as biological cues for scarless regenerative wound healing. Herein, we have investigated blends of silk fibroin and honey as a wound healing substrate that able to facilitate keratinocyte and fibroblast adhesion, migration and proliferation. Honey-silk fibroin (HSF) three dimensional (3D) scaffolds were fabricated by freeze drying and characterized in detailed for their physicochemical, mechanical, swelling and degradable properties. Interestingly, in vitro studies showed better adhesion, proliferation and homogenous distribution of fibroblasts within blended scaffolds especially with 4% honey concentration (HSF4). Also, its structural composition with pores size similar to 139 mu m and porosity 87% further confirms the superiority over the counterparts and other blended scaffolds. The in vitro cytotoxic studies illustrated the biocompatibility, proliferation and proper infiltration of primary fibroblasts within HSF4 scaffolds, validated by in vivo studies. Fascinatingly, in vivo cutaneous wound healing studies demonstrated the attainment of normal homeostasis with proper re-epithelialization, collagen matrix remodeling having high collagen I expression in respect to collagen III with minimal scar under HSF4 scaffold implantation. Taken together, this study suggests the potentiality of incorporation of honey component as a payload which not only augmented the scarless healing also modified the physical properties of scaffold in order to provide the suitable micro-ambience for healing and these material scaffold proved to be a potential dermal substitute for acute as well as chronic wounds. Statement of Significance The 3D honey based porous scaffolds are increasingly getting attention in the field of biomedicine and wound healing due to their ability to mimic the architecture of native microenvironment and could provide the controlled release of honey at the affected area for fast regeneration. In this work we demonstrated that the addition of honey in SF scaffold not only enhanced the biological activity of scaffold also modulated the physico-chemical properties which ultimately helps in attaining fast homeostatic wound healing. The synergy of pore size, porosity and mechanical strength of scaffold having 4% honey concentration showed its potentiality in augmenting proper re-epithelialization, collagen matrix deposition and skin appendages formation which presents this scaffold as potential candidate in skin tissue engineering applications.

We report potentiation of healing efficacy of alginate by value addition at its structural level. Dual crosslinked (ionically and covalently) sodium alginate hydrogel coupled with honey (HSAG) brings about an intermediate stiffness in the fabric, confers consistent swelling property and limits erratic degradation of the polymer which ultimately provides conducive milieu to cellular growth and proliferation. In this work honey concentrations in HSAGs are varied from 2% to 10%. FTIR, XRD and nanoindentation studies on the HSAGs exhibited physicochemical integrity. In vitro degradation study provided the crucial finding on 4% HSAG having controlled degradation rate up to 12 days with a weight loss of 87.36 ± 1.14%. This particular substrate also has an ordered crystalline surface morphology with decent cellular viability (HaCaT and 3T3) and antimicrobial potential against Methicillin Resistant Staphylococcus aureus (MRSA) and Escherichia coli. The in vivo wound contraction kinetics on murine models (4% HSAG treated wound contraction: 94.56 ± 0.1%) has been monitored by both invasive (histopathology) and noninvasive (Swept Source Optical Coherence Tomography) imaging and upon corroborating them it evidenced that 4% HSAG treated wound closure achieved epithelial thickness resembling to that of unwounded skin. Thus, the work highlights structurally modified alginate hydrogel embedded with honey as a potential antimicrobial healing agent.

•Prevalence of a global pandemic like Diabetes Mellitus intensifies the ultimatum of wound persistence.•ROS generation, nerve deterioration by hyperactive mitochondria and hyperglycemia does havoc in pathogenesis of chronic wound.•Multifaceted system pathology makes treatment of diabetic wound quite recalcitrant due to association of cellular and molecular oddity.•From primeval times the legacy of honey has continued in traditional medicine and notably in the treatment of wound healing.•The colossal domain of biological activities of honey infringes diabetic wound pathology to augment regenerative healing windows.

Event Abstract Back to Event Fabrication and optimization of 2D alginate membranes for regenerative medicine and tissue engineering application Anurup Mukhopadhyay1, Monika Rajput1, Rabibrata Mukherjee2, Provas Banerjee3 and Jyotirmoy Chatterjee1 1 Indian Institute of Technology, School of Medical Science and Technology, India 2 Indian Institute of Technology, Department of Chemical Engineering, India 3 Banerjees' Biomedical Research Foundation, India Introduction: Tissue engineering approaches provide crucial exogenous support for tissue regeneration and reparative processes, particularly for the maintenance of tissue integrity during restoration of the damaged or lost one .These endeavors have to overcome varied challenges especially to mimic target tissue micro-environment with bio-compatible construct. In this juncture, alginate has been used due to its good biocompatibility and mechanical strength[1]. Foremost challenge remains in controlling fast degradation of membranes under in vitro and in vivo conditions due to lack of proper stability coming from disoriented entanglement of fibers. Present study focuses on the aforesaid optimization, thorough physical & chemical characterization of the membranes and subsequent application on acute wound animal model to check therapeutic efficacy[2]. Materials and Method: In this study, alginate 2D membranes of 2, 4, 6 and 8% concentrations were fabricated by drop casting technique. The membranes were optimized by different ratios of Carbodiimide crosslinker and ethanol concentrations. Fabricated membranes were further characterized physicochemically for surface topography, mechanical strength, degradation, swelling behavior and chemical integrity by SEM, Utensile Testing Machine (UTM), FTIR and XRD, respectively[3]. MTT assay was carried out for 7 days to assess the biological activity of cells on optimized membranes[4]. Results and Discussion: The present study illustrates 4% alginate concentration to be with sufficient amount of molecular entanglement contributing to sublime stability after being crosslinked with a mixture of 85% ethanol and 0.05mM carbodiimide which was optimized by trying with varied concentrations by FTIR and XRD. Optimized membrane demonstrated enhanced tensile strength, swelling behavior and slow biodegradability rate with graduation of time. In comparison to other concentrations, 4% showed good biocompatibility on optimized membranes along with improved proliferation rate of cells at all considered time points. Conclusion: The crosslinked 2D alginate membrane with enhanced physical, chemical and biological properties ensures their future application as a suitable external bioscaffold in regenerative medicine and tissue engineering field. Non-Invasive Characterization Of Healing And Non-Healing Wounds And Development Of Honey-Biomaterial And Stem Cell Based Wound Therapy (NIC), Indian Institute Of Technology, Kharagpur, West BengalReferences:[1] Barui A, Banerjee P, KumarDas R, Dhara S, Chatterjee J. Honey based fibrous scaffold for tissue engineering application. Life Science Systems and Applications Workshop (LiSSA), 2011 IEEE/NIH: IEEE; 2011. p. 83-5[2] Lee KY, Mooney DJ. Alginate: properties and biomedical applications. Progress in polymer science 2012;37:106-26[3] N. Bhattarai, Z. Li, D. Edmondson, M. ZhangAlginate-based nanofibrous scaffolds: structural, mechanical, and biological properties Adv. Mater., 18 (2006), pp. 1463–1467[4] G. Skjåk-Braek Alginates: biosynthesis and some structure–function relationships relevant to biomedical and biotechnological applications Biochem. Soc. Trans., 20 (1992), pp. 27–33 Keywords: Regenerative Medicine, Tissue Engineering, Biocompatibility, surface topolography Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Regenerative medicine: biomaterials for control of tissue induction Citation: Mukhopadhyay A, Rajput M, Mukherjee R, Banerjee P and Chatterjee J (2016). Fabrication and optimization of 2D alginate membranes for regenerative medicine and tissue engineering application. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00171 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anurup Mukhopadhyay Monika Rajput Rabibrata Mukherjee Provas Banerjee Jyotirmoy Chatterjee Google Anurup Mukhopadhyay Monika Rajput Rabibrata Mukherjee Provas Banerjee Jyotirmoy Chatterjee Google Scholar Anurup Mukhopadhyay Monika Rajput Rabibrata Mukherjee Provas Banerjee Jyotirmoy Chatterjee PubMed Anurup Mukhopadhyay Monika Rajput Rabibrata Mukherjee Provas Banerjee Jyotirmoy Chatterjee Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

A significant amount of India's population is known to suffer from malnutrition despite several efforts and ventures throughout the country. A comparative study on mothers ’perception towards their children's (school going) diet conducted in Barasat and Baranagar regions of Kolkata has proved the validity of this statement. The survey included basic questionnaires to a total of 203 mothers of school kids, categorized based on the ages of their children viz., Group A (2 to 3 years), Group B (3 to 4 years), Group C (4–5 years) and Group D (5 to 6 years). It was apparent from the study that mothers from the regions have insufficient knowledge about their kid's nutritional requirements. This study can be expected to bring about a positive response such that mothers should be encouraged to pay further attention towards their children's diet and healthy food habits to avoid this curse of malnutrition.