creates a defect that intra-abdominal contents may protrude through. [1] The most common types of hernias are incisional, inguinal, femoral, umbilical and hiatal hernias. [2] Hernia repair for many defects is performed by the surgical implantation of a prosthetic mesh to firmly support and reinforce the damaged abdominal wall and facilitate the healing process (Figure 1A,B). Each year, over 400 000 incisional hernia repair surgeries are performed with a cost of ≈$15 billion in US healthcare expenditures. [3-5] Prosthetic hernia mesh implants are developed using synthetic, biologic, and coated materials. [6,7] Despite their specific advantages, these mesh implants are not very effective in minimizing potential adverse postsurgical complications. [8] Surgical hernia repair with mesh implants mostly fail due to the formation of visceral adhesions, hardening, and shrinking of the mesh after its implantation. Visceral adhesions are fibrous tissues developed from the underlying serosal membrane of stomach, intestine or colon, that attach to the implanted mesh. [9] These adhesions are mainly composed of collagen and fibroblasts that grow on the mesh and adhere to the nearby tissue, nerves and organs. [10] The mesh shrinks as the adhesions grow and scar tissue hardens, thus forming a hard, fibrous mass that may cause chronic pain, bowel obstruction, enteric fistula, infertility, poor quality of life, and failure of the surgical hernia repair. [11-13] To remove the failed hernia mesh, a complicated surgery needs to be performed, wherein the mesh must be peeled off bladder, stomach, intestine, colon, or a major blood vessel, that may adversely affect the clinical outcomes. [14] To minimize adhesions formation, graft contraction, and foreign body reactions, absorbable and biological meshes have been developed. However, these meshes are not significantly effective because of very high hernia recurrence rates. [15-17] Causative factors for adverse complications arising due to surgical mesh implantation are chronic inflammatory responses, poor mesh-tissue integration, rapid degradation of the materials, surface chemistry and topochemical design of the mesh. [18,19] We herein present the development of an intrinsically inflammation modulating 3D-fabricated biomaterial scaffold (bioscaffold) for soft tissue repair and demonstrate its in vivo efficacy in a rat ventral hernia Development of inflammation modulating polymer scaffolds for soft tissue repair with minimal postsurgical complications is a compelling clinical need. However, the current standard of care soft tissue repair meshes for hernia repair is highly inflammatory and initiates a dysregulated inflammatory process causing visceral adhesions and postsurgical complications. Herein, the development of an inflammation modulating biomaterial scaffold (bioscaffold) for soft tissue repair is presented. The bioscaffold design is based on the idea that, if the excess proinflammatory cytokines are sequestered from the site of injury by the surgical implantation of a bioscaffold,...

Diseases affecting the retina, such as age-related macular degeneration (AMD), diabetic retinopathy, macular edema, and retinal vein occlusions, are currently treated by the intravitreal injection of drug formulations. These disease pathologies are driven by oxidative damage due to chronic high concentrations of reactive oxygen species (ROS) in the retina. Intravitreal injections often induce retinal detachment, intraocular hemorrhage, and endophthalmitis. Furthermore, the severe eye pain associated with these injections lead to patient noncompliance and treatment discontinuation. Hence, there is a critical need for the development of a noninvasive therapy that is effective for a prolonged period for treating retinal diseases. In this study, we developed a noninvasive cerium oxide nanoparticle (CNP) delivery wafer (Cerawafer) for the modulation of ROS in the retina. We fabricated Cerawafer loaded with CNP and determined its SOD-like enzyme-mimetic activity and ability to neutralize ROS generated in vitro. We demonstrated Cerawafer's ability to deliver CNP in a noninvasive fashion to the retina in healthy mouse eyes and the CNP retention in the retina for more than a week. Our studies have demonstrated the in vivo efficacy of the Cerawafer to modulate ROS and associated downregulation of VEGF expression in the retinas of very-low-density lipoprotein receptor knockout (vldlr−/−) mouse model. The development of a Cerawafer nanotherapeutic will fulfill a hitherto unmet need. Currently, there is no such therapeutic available, and the development of a Cerawafer nanotherapeutic will be a major advancement in the treatment of retinal diseases.

Eye injuries due to corneal abrasions, chemical spills, penetrating wounds, and microbial infections cause corneal scarring and opacification that result in impaired vision or blindness. However, presently available eye drop formulations of anti-inflammatory and antibiotic drugs are not effective due to their rapid clearance from the ocular surface or due to drug-related side effects such as cataract formation or increased intraocular pressure. In this article, we presented the development of a dextran sulfate-based polymer wafer (DS-wafer) for the effective modulation of inflammation and fibrosis and demonstrated its efficacy in two corneal injury models: corneal abrasion mouse model and alkali induced ocular burn mouse model. The DS-wafers were fabricated by the electrospinning method. We assessed the efficacy of the DS-wafer by light microscopy, qPCR, confocal fluorescence imaging, and histopathological analysis. These studies demonstrated that the DS-wafer treatment is significantly effective in modulating corneal inflammation and fibrosis and inhibited corneal scarring and opacification compared to the unsulfated dextran-wafer treated and untreated corneas. Furthermore, these studies have demonstrated the efficacy of dextran sulfate as an anti-inflammatory and antifibrotic polymer therapeutic.