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Hydrogels are excellent wound healing materials. However, due to the wear and tear at the wound site, hydrogels can lose their structural and functional integrity. To overcome this and to effectively seal the wound and control infection, an in-situ silver nanoparticles (AgNps) incorporated N, O-carboxymethyl chitosan (N, O-CMC) based self-healing hydrogel using ethylenediaminetetraacetic acid-ferric ion (EDTA: Fe3+) complex was developed. The prepared N, O-CMC/AgNps hydrogel was characterized using FTIR, SEM, and TEM. The developed N, O-CMC/AgNps hydrogel was found to be adhesive, injectable, conductive, bio-compatible, and showed antibacterial activity against ATCC and clinical strains of E. coli, K. pneumonia, P. aeruginosa, S. aureus and MRSA. N, O-CMC/AgNps hydrogel also showed anti-biofilm activity against S. aureus, E. coli, and P. aeruginosa (ATCC strains). This developed antibacterial and self-healing N, O-CMC/AgNps hydrogel can be used in the treatment of infected wounds.

One of the major risks of cardiac surgery is the occurrence of infection at the sternal wound site. Sternal wound infections are primarily classified into superficial infection and deep sternal wound infection or mediastinitis. A patient is diagnosed with mediastinitis if microorganisms are present in their mediastinal tissue/fluid or with the observation of sternal wound infection during operation and with characteristic symptoms including chest pain, fever, and purulent drainage from the mediastinum. It is usually caused by Staphylococcal organisms in 75.8% of cases and the rest is caused by gram-negative bacteria. Currently, in cardiac surgery, hemostasis is achieved using electrocautery and bone wax, and the sternum is closed using wire cerclage. Several studies show that bone wax can act as a nidus for initiation of infection and the oozing blood and hematoma at the site can promote the growth of infectious organisms. Many research groups have developed different types of biomaterials and reported on the prevention of infection and healing of the sternum. These materials are reported to have both positive and negative effects. In this review, we highlight the current clinical practices undertaken to prevent infection and bleeding as well as research progress in this field and their outcomes in controlling bleeding, infection, and enhancing sternal healing.

Tendon being a hypocellular, low vascularized tissue often requires assistance for restoration after complete tear. Tendon tissue engineering aims in the development of suitable scaffold that could support the regeneration of tendon after damage. The success of such scaffolds is dependent on its integration with the native tissue which in turn is influenced by the cell-material interaction. In this work aligned poly(ε-caprolactone)/collagen (PCL/collagen) multiscale fibers were developed and plasma treatment using argon, nitrogen and its combination was accessed for inducing tenogenic differentiation in mesenchymal stem cells. The developed fibers mimicked tendon extracellular matrix (ECM) which upon plasma treatment maintained moderate hydrophilicity. Oxygen and nitrogen containing groups were observed to be incorporated after argon and nitrogen treatment respectively. Statistically significant (p 0.001) enhancement was observed in average and root mean square (RMS) roughness after plasma treatment with the maximum in argon treated fibers. Vitronectin was competitively (statistically significant, p 0.05) adsorbed after argon and combination treatment whereas nitrogen treatment led to the competitive adsorption of fibronectin (statistically significant, p 0.05). Human mesenchymal stem cells (hMSCs) showed enhanced proliferation and attachment on plasma treated fibers. Increased porosity due to the presence of sacrificial collagen nanofibers improved cell infiltration which was further enhanced upon plasma treatment. RhoA activation was observed (statistically significant, p 0.05) on aligned PCL/collagen multiscale fibers and PCL microfibers, which proved its impact on tenogenic differentiation. Further enhancement in rhoA expression was observed on argon (p 0.01) and combination plasma (p 0.05) treated fibers. Tenogenic differentiation of hMSCs was enhanced (statistically significant) on argon plasma treated aligned fibers which was confirmed by the expression of scleraxis, mohawk (early markers) and tenomodulin (late marker) at protein level and mohawk, collagen I, collagen III (early markers), thrombospondin 4 and tenascin C (late markers) at gene level. Thus argon plasma treatment on aligned fibers is an effective method to induce tenogenesis even in non-tenogenic media.

Recent years have seen tremendous interest among researchers in the field of biosensors for the application of medical and agricultural products, processed food, and environmental monitoring. To prepare a stable and reliable biosensor, immobilization of biological responses elements (BRE) plays a critical role. Chitosan, a natural polysaccharide with non-toxic and gellable properties, and the presence of functional groups would act as a suitable substrate material. The presence of functional groups would provide cross-linking moieties increasing the mechanical stability, immobilization of BRE and nanomaterials. Additionally, a chitosan composite/nanocomposite-based biosensor would provide enhanced conductivity and sensitivity of detecting various biological analytes such as glucose, H2O2, antigens, DNA, and biomolecules. This review provides a comprehensive understanding of various strategies of utilizing chitosan as a substrate for various biosensing applications.

Chitosan is a cationic biopolymer that is derived from chitin by the alkaline deacetylation technique. It has randomly distributed d-glucosamine and N-Acetyl-d-glucosamine units in its backbone. Due to the presence of primary hydroxyl and amino groups, chitosan can be modified into various derivatives with desired functionalities. Chitosan and its derivatives are considered as potential biomaterials to be utilized in various biological applications because of their easy availability, nontoxicity, biocompatibility, biodegradability, and gelling properties. This chapter provides a detailed review on the current status and challenges of using chitosan-based materials as biosensors, food coatings, drug delivery carriers, antimicrobial agents, wound dressings, hemostatic agents, and tissue engineering scaffolds.

Calcium-based injectable hydrogels with various bioactive active molecules possess a great potential for bone regeneration. Herein, we have synthesized a chitin-PLGA-calcium sulfate hydrogel (CSG) containing bioactive molecules - lactoferrin (LF) and substance P (SP). SEM and XRD analysis revealed that CS crystal growth was altered with the addition of LF. Rheological measurements indicated that the injectability of the hydrogels was maintained after the addition of LF, however, there was a reduction in storage modulus after LF addition. The addition of LF increased stem cell proliferation whereas, SP enhanced the cell migration. Osteogenic gene expression revealed that LF concentration at 25 μg/mg of CSG was optimal for a favourable outcome. To this optimized LF containing CSG, SP was incorporated and 0.05 μg/mg was found to be most effective (CSG-L3S2) in vitro studies. Further, the μ-CT and histological studies confirmed that CSG-L3S2 showed enhanced bone regeneration compared to the controls in critical-sized calvarial defect of mice. Thus the results indicate that a combination of the chemotactic agent (SP), pleiotropic growth protein (LF), and CS in the chitin-PLGA hydrogel could be a promising approach for non-load bearing bone defects.

Hypoxia is a condition that gradually leads to ischemic damages in organs which is marked by poor tissue perfusion. Depending on the severity of the condition, revascularisation therapies are needed for reducing the risk of organ dysfunction. This study was aimed at developing an injectable nanocurcumin and arginine incorporated chitosan hydrogel (nC/R) that can prevent hypoxia induced endothelial damage. The prepared hydrogel has shear thinning, stable and injectable nature. The (nC and nC/R) hydrogels showed significant antioxidant activity and biodegradation in vitro. The release of curucmin and arginine from the nC/R was found to be higher at acidic pH, which predominates in an ischemic site. To mimic low oxygen environment, an in vitro hypoxic endothelial dysfunction model was developed which showed decreased expressions of phosphorylated eNOS (serine 1177) when compared to the cells cultured in normoxic condition. In vitro tube formation assay demonstrated the protective effect of nC/R towards hypoxia induced reduction of tube width. The nC/R hydrogel was found to enhance phosphorylation of eNOS at serine 1177 site in cultured endothelial cells subjected to hypoxia. Therefore, nC/R hydrogel could effectively deliver both curcumin and arginine and therapeutically reduce the effect of hypoxia induced endothelial dysfunction.

BACKGROUND: Human adipose tissue is a great source of translatable biomaterials owing to its ease of availability and simple processing. Reusing discardable adipose tissue for tissue regeneration helps in mimicking the exact native microenvironment of tissue. Over the past 10 years, extraction, processing, tuning and fabrication of adipose tissue have grabbed the attention owing to their native therapeutic and regenerative potential. The present work gives the overview of next generation biomaterials derived from human adipose tissue and their development with clinical relevance. METHODS: Around 300 articles have been reviewed to widen the knowledge on the isolation, characterization techniques and medical applications of human adipose tissue and its derivatives from bench to bedside. The prospective applications of adipose tissue derivatives like autologous fat graft, stromal vascular fraction, stem cells, preadipocyte, adipokines and extracellular matrix, their behavioural mechanism, rational property of providing native bioenvironment, circumventing their translational abilities, recent advances in featuring them clinically have been reviewed extensively to reveal the dormant side of human adipose tissue. RESULTS: Basic understanding about the molecular and structural aspect of human adipose tissue is necessary to employ it constructively. This review has nailed the productive usage of human adipose tissue, in a stepwise manner from exploring the methods of extracting derivatives, concerns during processing and its formulations to turning them into functional biomaterials. Their performance as functional biomaterials for skin regeneration, wound healing, soft tissue defects, stem cell and other regenerative therapies under in vitro and in vivo conditions emphasizes the translational efficiency of adipose tissue derivatives. CONCLUSION: In the recent years, research interest has inclination towards constructive tissue engineering and regenerative therapies. Unravelling the maximum utilization of human adipose tissue derivatives paves a way for improving existing tissue regeneration and cellular based therapies and other biomedical applications.

Sreeranganathan M, Uthaman S, Sarmento B, et al. Int JNanomedicine. 2017;12:7165–7182. When reviewing the paper, the authors noted some errorsin Figure 2E (page 7171) and Figure 6 (page 7176). Theyconfirm that the corrections to Figures 2 and 6 do not alterthe inferences or conclusion of the respective figures, northe overall conclusion of the article, and apologize for thisinadvertent error. In the original manuscript, Figure 2 represents the cellularinternalization of the nanoparticles and Figure 2E representsthe uptake of targeted nanoparticles by MKN-28 cells at ahigher magnification. In Figure 2E, the fluorescence imagewas wrongly merged with the incorrect brightfield image ofthe cell. The authors have rectified this mistake by replacingFigure 2E with the confocal microscope image using thecorrect phase contrast, fluorescent, and merged images. Thecorrected version of Figure 2 is included as follows. Read the original article &nbsp

Mohandas A, Kumar PT S, Raja B, et al. Int J Nanomedicine.2015;10(Suppl 1):53–66. The authors have advised that Figure 8B and C (page62) were incorrect in the original manuscript, as theAlginate control group is inadvertently repeated in theAlginate +0.1% nZnO group. Due to this mistake theyhave repeated the entire cell attachment studies usingDAPI. The authors have confirmed that this does not inany way affect the conclusions from Figure 8B and C,and that it is not going to affect the overall conclusionof this published paper. They apologize for any inconvenience.The correct version of Figure 8 is presentedbelow. Read the original article

Calcium-based injectable hydrogels with various bioactive active molecules possess a great potential for bone regeneration. Herein, we have synthesized a chitin-PLGA-calcium sulfate hydrogel (CSG) containing bioactive molecules - lactoferrin (LF) and substance P (SP). SEM and XRD analysis revealed that CS crystal growth was altered with the addition of LF. Rheological measurements indicated that the injectability of the hydrogels was maintained after the addition of LF, however, there was a reduction in storage modulus after LF addition. The addition of LF increased stem cell proliferation whereas, SP enhanced the cell migration. Osteogenic gene expression revealed that LF concentration at 25 μg/mg of CSG was optimal for a favourable outcome. To this optimized LF containing CSG, SP was incorporated and 0.05 μg/mg was found to be most effective (CSG-L3S2) in vitro studies. Further, the μ-CT and histological studies confirmed that CSG-L3S2 showed enhanced bone regeneration compared to the controls in critical-sized calvarial defect of mice. Thus the results indicate that a combination of the chemotactic agent (SP), pleiotropic growth protein (LF), and CS in the chitin-PLGA hydrogel could be a promising approach for non-load bearing bone defects.

Chitosan (Cs) as a hemostatic agent has been in use to control hemorrage. Composite hydrogel formed by entrapment of vasoconstrictor-potassium aluminium sulfate (0.25 %PA) and coagulation activator-calcium chloride (0.25 %Ca) into Cs (2 %) hydrogel would enhance the hemostatic property of Cs. In this work, the prepared composite hydrogel was injectable, shear thinning, cyto and hemocompatible. The 2 %Cs-0.25 %PA-0.25 %Ca composite hydrogel caused rapid blood clotting by accelerating RBC/platelet aggregation and activation of the coagulation cascade. Further, in vivo studies on rat liver and femoral artery hemorrage model showed the efficiency of 2 %Cs-0.25 %PA-0.25 %Ca composite hydrogel to achieve hemostasis in a shorter time (20 ± 10 s, 105 ± 31 s) than commercial hemostatic agents-Fibrin sealant (77 ± 26 s, 204 ± 58 s) and Floseal (76 ± 15 s, 218 ± 46 s). In in vivo toxicological study, composite hydrogel showed material retention even after 8 weeks post-surgery, therefore excess hydrogel should be irrigated from site of application. This prepared composite hydrogel based hemostatic agent has potential application in low pressure bleeding sites.

The intracellular and biofilm associated bacterial infections are difficult to treat due to the resistance potential of the organisms toward commonly used antimicrobial agents. Nanoparticles have promising future in the development of new therapeutics because of their easy functionalization and unique mode of action. This book chapter consists of three parts. The first two parts explain the limitations in the treatment of intracellular and biofilm infections in the current scenario. The last part describes how nanoparticles can be employed to tackle the problems of drug resistance and the latest research studies conducted regarding the same.