Nanocellulose has recently attracted a great deal of attention for numerous biomedical applications due to its superior mechanical properties, high surface area, tailorable surface chemistry, good biocompatibility, renewable nature, and cost-effectiveness. The objective of this study was to investigate the long-term in vivo biocompatibility of three kinds of nanocellulose, namely, cellulose nanocrystal (CNC), cellulose nanofiber (CNF), and TEMPO-oxidized cellulose nanofiber (TOCNF). The morphological features of these nanocellulose materials were examined by transmission electron microscopy. In vivo biocompatibility of all nanocellulose materials was investigated using a subcutaneous rat model for 1, 2, 4, and 12 weeks of implantation. The average diameters of prepared homogenous CNC, CNF, and TOCNF were ∼6 nm, ∼8 nm, and ∼5 nm respectively, as depicted by micrographs obtained by using transmission electron microscopy. TOCNF showed highest in vitro biocompatibility with respect to CNC and CNF in response to L929 fibroblast cells. In vivo studies revealed that all nanocellulose materials exhibited no foreign body reaction up to two-week post-injection. Subcutaneous implantation at 12 weeks showed lowest inflammation and better tissue repair for TOCNF compared to CNC and CNF. The results suggest that the long-term biocompatibility profile follows the sequence: TOCNF > CNC > CNF.

Hyperglycemia plays a key role in the development of microvascular complications, endothelial dysfunction (ED), and inflammation. It has been demonstrated that cathepsin S (CTSS) is activated in hyperglycemia and is involved in inducing the release of inflammatory cytokines. We hypothesized that blocking CTSS might alleviate the inflammatory responses and reduce the microvascular complications and angiogenesis in hyperglycemic conditions. In this study, we treated human umbilical vein endothelial cells (HUVECs) with high glucose (HG; 30 mM) to induce hyperglycemia and measured the expression of inflammatory cytokines. When treated with glucose, hyperosmolarity could be linked to cathepsin S expression; however, many have mentioned the high expression of CTSS. Thus, we made an effort to concentrate on the immunomodulatory role of the CTSS knockdown in high glucose conditions. We validated that the HG treatment upregulated the expression of inflammatory cytokines and CTSS in HUVEC. Further, siRNA treatment significantly downregulated CTSS expression along with inflammatory marker levels by inhibiting the nuclear factor-kappa B (NF-κB) mediated signaling pathway. In addition, CTSS silencing led to the decreased expression of vascular endothelial markers and downregulated angiogenic activity in HUVECs, which was confirmed by a tube formation experiment. Concurrently, siRNA treatment reduced the activation of complement proteins C3a and C5a in HUVECs under hyperglycemic conditions. These findings show that CTSS silencing significantly reduces hyperglycemia-induced vascular inflammation. Hence, CTSS may be a novel target for preventing diabetes-induced microvascular complications.

Breast augmentations with silicone implants can have adverse effects on tissues that, in turn, lead to capsular contracture (CC). One of the potential ways of overcoming CC is to control the implant/host interaction using immunomodulatory agents. Recently, a high ratio of anti-inflammatory (M2) macrophages to pro-inflammatory (M1) macrophages has been reported to be an effective tissue regeneration approach at the implant site. In this study, a biofunctionalized implant was coated with interleukin (IL)-4 to inhibit an adverse immune reaction and promoted tissue regeneration by promoting polarization of macrophages into the M2 pro-healing phenotype in the long term. Surface wettability, nitrogen content, and atomic force microscopy data clearly showed the successful immobilization of IL-4 on the silicone implant. Furthermore, in vitro results revealed that IL-4-coated implants were able to decrease the secretion of inflammatory cytokines (IL-6 and tumor necrosis factor-α) and induced the production of IL-10 and the upregulation of arginase-1 (mannose receptor expressed by M2 macrophage). The efficacy of this immunomodulatory implant was further demonstrated in an in vivo rat model. The animal study showed that the presence of IL-4 diminished the capsule thickness, the amount of collagen, tissue inflammation, and the infiltration of fibroblasts and myofibroblasts. These results suggest that macrophage phenotype modulation can effectively reduce inflammation and fibrous CC on a silicone implant conjugated with IL-4.

During development of functional tissue engineered vascular graft, ensuring endothelialization at inner layer and mechanically strong outer layer is considered as challenging. The study objective was to fabricate a multilayered artificial blood vessel by dual syringe electrospinning technique. The presented graft was composed of polycaprolactone-methoxy polyethylene glycol which acts as an inner layer whereas Poly [4,4’-methylenebis(phenyl isocyanate)-alt-1,4-butanediol/di(propylene glycol)/polycaprolactone] (PUPCL) (12% w/v) was incorporated as the outer layer. To find out the optimum inner layer, different polycaprolactone-methoxy polyethylene glycol electrospun membranes varying methoxy polyethylene glycol content (0, 5, 10, 20, and 30% w/v) were prepared and evaluated. The characterizations revealed that blending of methoxy polyethylene glycol with polycaprolactone improved hydrophilicity and antithrombogenic properties compared to polycaprolactone or polyurethane polycaprolactone membrane. During in vitro assessment, the optimized polycaprolactone-20% methoxy polyethylene glycol membrane reinforced a greater differentiation of rat bone marrow stem cell into endothelial cells at both mRNA and protein levels by significantly inducing endothelial markers (CD31, Flk-1, and von Willebrand factor) expression. The polyurethane polycaprolactone membrane showed higher mechanical strength than polycaprolactone-methoxy polyethylene glycol while multilayered polycaprolactone-20% methoxy polyethylene glycol/polyurethane polycaprolactone vascular graft exhibited better result compared to single form. Therefore, the strong and bioactive polycaprolactone-20% methoxy polyethylene glycol/polyurethane polycaprolactone small diameter graft (<2 mm) prepared by simple fabrication process could be a promising preliminary platform for vascular tissue engineering application studies.

Breast reconstruction is achieved using silicone implants, which are currently associated with major complications. Several strategies have been considered to overcome the existing limitations as well as to improve their performance. Recently, surface modification has proved to be an effective clinical approach to prevent bacterial adhesion, reduce capsular thickness, prevent foreign body reactions, and reduce other implant-associated problems. This review article summarizes the ongoing strategies for the surface modification of silicone implants in breast reconstruction applications. The article mostly discusses two broad categories of surface modification: drug-mediated and polymer-based. Different kinds of drugs have been applied with silicone that are associated with breast reconstruction. Initially, this article discusses studies related to drugs immobilized on silicone implants, focusing on drug-loading methods and their effects on capsule contracture. Moreover, the pharmacological action of drugs on fibroblast cells is considered in this section. Next, the polymeric modification of the silicone surface is introduced, and we discuss its role in reducing capsule thickness at the cellular and biological levels. The polymeric modification techniques, their chemistry, and their physical properties are described in detail. Notably, polymer activities on macrophages and inflammation are also briefly discussed. Each of the reviewed articles is summarized, highlighting their discussion of capsular thickness, foreign body reactions, and bacterial attachment. The aim of this review is to provide the main points of some research articles regarding the surface modification of silicon, which can lead to a decrease in capsular thickness and provides better patient compliance.