Impaired wound healing is a major complication of diabetes, and can lead to development of chronic foot ulcers in a significant number of patients. Despite the danger posed by poor healing, very few ...specific therapies exist, leaving patients at risk of hospitalization, amputation, and further decline in overall health. Recent Advances: Redox signaling is a key regulator of wound healing, especially through its influence on the extracellular matrix (ECM). Normal redox signaling is disrupted in diabetes leading to several pathological mechanisms that alter the balance between reactive oxygen species (ROS) generation and scavenging. Importantly, pathological oxidative stress can alter ECM structure and function.
There is limited understanding of the specific role of altered redox signaling in the diabetic wound, although there is evidence that ROS are involved in the underlying pathology.
Preclinical studies of antioxidant-based therapies for diabetic wound healing have yielded promising results. Redox-based therapeutics constitute a novel approach for the treatment of wounds in diabetes patients that deserve further investigation. Antioxid. Redox Signal. 27, 823-838.
Extracellular matrix (ECM) derived components are emerging sources for the engineering of biomaterials that are capable of inducing desirable cell-specific responses. This review explores the use of ...biomaterials derived from naturally occurring ECM proteins and their derivatives in approaches that aim to regulate cell function. Biomaterials addressed are grouped into six categories: purified single ECM proteins, combinations of purified ECM proteins, cell-derived ECM, tissue-derived ECM, diseased and modified ECM, and ECM-polymer coupled biomaterials. Purified ECM proteins serve as a material coating for enhanced cell adhesion and biocompatibility. Cell-derived and tissue-derived ECM, generated by cell isolation and decellularization technologies, can capture the native state of the ECM environment and guide cell migration and alignment patterns as well as stem cell differentiation. We focus primarily on recent advances in the fields of soft tissue, cardiac, and dermal repair, and explore the utilization of ECM proteins as biomaterials to engineer cell responses.
Nanomaterials, Inflammation, and Tissue Engineering Padmanabhan, Jagannath; Kyriakides, Themis R.
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology,
May/June 2015, Letnik:
7, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Nanomaterials exhibit unique properties that are absent in the bulk material because decreasing material size leads to an exponential increase in surface area, surface area to volume ratio, and ...effective stiffness, resulting in altered physiochemical properties. Diverse categories of nanomaterials such as nanoparticles, nanoporous scaffolds, nanopatterned surfaces, nanofibers, and carbon nanotubes can be generated using advanced fabrication and processing techniques. These materials are being increasingly incorporated in tissue engineering scaffolds to facilitate the development of biomimetic substitutes to replace damaged tissues and organs. Long‐term success of nanomaterials in tissue engineering is contingent upon the inflammatory responses they elicit in vivo. This review seeks to summarize the recent developments in our understanding of biochemical and biophysical attributes of nanomaterials and the inflammatory responses they elicit, with a focus on strategies for nanomaterial design in tissue engineering applications. WIREs Nanomed Nanobiotechnol 2015, 7:355–370. doi: 10.1002/wnan.1320
This article is categorized under:
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Implantable Materials and Surgical Technologies > Nanomaterials and Implants
Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement
Impaired healing leading to the formation of ulcerated wounds is a critical concern in patients with diabetes. Abnormalities in extracellular matrix (ECM) production and remodeling contribute to ...tissue dysfunction and delayed healing. Specifically, diabetes-induced changes in the expression and/or activity of structural proteins, ECM-modifying enzymes, proteoglycans, and matricellular proteins have been reported. In this review, we provide a summary of the key ECM molecules and associated changes in skin and diabetic wounds. Such information should allow for new insights in the understanding of impaired wound healing and lead to the development of ECM-based therapeutic strategies.
•Wound healing is largely impaired in diabetes due, in part, to dysfunction and dysregulation of extracellular matrix.•This review gives a brief summary of the alterations of key ECM molecules in diabetes.•We also try to elucidate how hyperglycemia impacts ECM and anticipate how these changes contribute to the pathological state of diabetic wounds.
Numerous proteins and small leucine-rich proteoglycans (SLRPs) make up the composition of the extracellular matrix (ECM). Assembly of individual fibrillar components in the ECM, such as collagen, ...elastin, and fibronectin, is understood at the molecular level. In contrast, the incorporation of non-fibrillar components and their functions in the ECM are not fully understood.
This review will focus on the role of the matricellular protein thrombospondin (TSP) 2 in ECM assembly. Based on findings in TSP2-null mice and in vitro studies, we describe the participation of TSP2 in ECM assembly, cell–ECM interactions, and modulation of the levels of matrix metalloproteinases (MMPs).
Evidence summarized in this review suggests that TSP2 can influence collagen fibrillogenesis without being an integral component of fibrils. Altered ECM assembly and excessive breakdown of ECM can have both positive and negative consequences including increased angiogenesis during tissue repair and compromised cardiac tissue integrity, respectively.
Proper ECM assembly is critical for maintaining cell functions and providing structural support. Lack of TSP2 is associated with increased angiogenesis, in part, due to altered endothelial cell–ECM interactions. Therefore, minor changes in ECM composition can have profound effects on cell and tissue function. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
•TSP2 functions primarily as a modulator of cell–ECM interactions and can influence the assembly of ECM.•More importantly, TSP2-null ECM enhances angiogenic responses.•Therefore, strategies can be pursued to reduce TSP2 and generate novel ECM via decellularization techniques.
Abstract Poly(ethylene glycol) (PEG) hydrogels with their highly tunable properties are promising implantable materials, but as with all non-biological materials, they elicit a foreign body response ...(FBR). Recent studies, however, have shown that incorporating the oligopeptide RGD into PEG hydrogels reduces the FBR. To better understand the mechanisms involved and the role of RGD in mediating the FBR, PEG, PEG-RGD and PEG-RDG hydrogels were investigated. After a 28-day subcutaneous implantation in mice, a thinner and less dense fibrous capsule formed around PEG-RGD hydrogels, while PEG and PEG-RDG hydrogels exhibited stronger, but similar FBRs. Protein adsorption to the hydrogels, which is considered the first step in the FBR, was also characterized. In vitro experiments confirmed that serum proteins adsorbed to PEG-based hydrogels and were necessary to promote macrophage adhesion to PEG and PEG-RDG, but not PEG-RGD hydrogels. Proteins adsorbed to the hydrogels in vivo were identified using liquid chromatography-tandem mass spectrometry. The majority (245) of the total proteins (≥300) that were identified was present on all hydrogels with many proteins being associated with wounding and acute inflammation. These findings suggest that the FBR to PEG hydrogels may be mediated by the presence of inflammatory-related proteins adsorbed to the surface, but that macrophages appear to sense the underlying chemistry, which for RGD improves the FBR.
Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the ...non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulation. In this review, we discuss the molecular events that contribute to macrophage activation and fusion with a focus on the role of the inflammasome, signaling pathways such as JAK/STAT and NF-κB, and the putative involvement of micro RNAs in the regulation of these processes.
The PI3K/Akt pathway is necessary for several key endothelial cell (EC) functions, including cell growth, migration, survival, and vascular tone. However, existing literature supports the idea that ...Akt can be either pro- or antiangiogenic, possibly due to compensation by multiple isoforms in the EC when a single isoform is deleted. Thus, biochemical, genetic, and proteomic studies were conducted to examine isoform-substrate specificity for Akt1 vs. Akt2. In vitro, Akt1 preferentially phosphorylates endothelial nitric oxide synthase (eNOS) and promotes NO release, whereas nonphysiological overexpression of Akt2 can bypass the loss of Akt1. Conditional deletion of Akt1 in the EC, in the absence or presence of Akt2, retards retinal angiogenesis, implying that Akt1 exerts a nonredundant function during physiological angiogenesis. Finally, proteomic analysis of Akt substrates isolated from Akt1- or Akt2-deficient ECs documents that phosphorylation of multiple Akt substrates regulating angiogenic signaling is reduced in Akt1-deficient, but not Akt2-deficient, ECs, including eNOS and Forkhead box proteins. Therefore, Akt1 promotes angiogenesis largely due to phosphorylation and regulation of important downstream effectors that promote aspects of angiogenic signaling.
PDF
