Future Prospects of Proteolytic Enzymes and Wound Healing

Author(s):  
W. Westerhof
2003 ◽  
Vol 5 (23) ◽  
pp. 1-39 ◽  
Author(s):  
Marc A. Lafleur ◽  
Madeleine M. Handsley ◽  
Dylan R. Edwards

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is an integral part of physiological processes such as embryonic development, the female reproductive cycle and wound healing. Angiogenesis is also central to a variety of pathologies including cancer, where it is recognised as being crucial for the growth of solid tumours. Matrix metalloproteinases (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing number of modulators of cell function. Several of the MMPs, most notably MMP-2 and -9 and membrane-type-1 MMP (MT1-MMP), have been linked to angiogenesis. Potential roles for these proteases during the angiogenic process include degradation of the basement membrane and perivascular ECM components, liberation of angiogenic factors, production of endogenous angiogenic inhibitors, and the unmasking of cryptic biologically relevant sites in ECM components. This review brings together what is currently known about the functions of the MMPs and the closely related adamalysin metalloproteinase (ADAM) family in angiogenesis, and discusses how this information might be useful in manipulation of the angiogenic process, with a view to controlling aberrant neovascularisation.


2021 ◽  
Vol 27 ◽  
Author(s):  
Hitesh Chopra ◽  
Shweta Gandhi ◽  
Rupesh Kumar Gautam ◽  
Mohammad Amjad Kamal

: Although there is a big heap of treatment options available for the wound and burns dressings, improvements in technology are still required. Bacterial cellulose is a polymer derived from the microbiological world and has shown some promising properties that recommend it as a wound healing therapeutic. Moreover, bacterial cellulose can be nanosized to form Bacterial Nanocellulose (BNC), enhancing its properties. Most importantly, in addition to its inherent antibacterial properties, BNC can be used to deliver drugs. This article presents a birds-eye view of the preparation method and applications of BNC based wound dressings.


1996 ◽  
Vol 43 (3) ◽  
pp. 557-565 ◽  
Author(s):  
M Cechowska-Pasko ◽  
J Pałka ◽  
E Bańkowski

In the skin of diabetic animal tissues the amount of extracellular matrix (ECM) components is drastically decreased as a result of a reduced rate of their biosynthesis or increased degradation. In the present study we have investigated the mechanism of poor wound healing in diabetic rats. We have found that wounded skin of diabetic rats shows a significant decrease in glycosaminoglycan (GAG) content compared to that of control animals. This decrease was accompanied by significant depletion of insulin-like growth factor-I (IGF-I), known as a stimulator of GAG biosynthesis, and a distinct decrease in the content of high molecular weight IGF-binding proteins (HMW-BPs) with a simultaneous increase in low molecular weight IGF-binding proteins (LMW-BPs) in the sera of diabetic animals. Basing on determination of proteolytic activities we suggest that insulin shortage in diabetes results in increased proteolytic activity in various tissues. Proteolytic enzymes may cleave the HMW-BPs and convert them to LMW-BPs. The LMW-BPs may inactivate IGF-I and eliminate its stimulatory effects on GAG biosynthesis. The proteolytic enzymes may also digest the protein cores of proteoglycans releasing the GAGs and making them more susceptible to the action of glycosidases. These phenomena may be responsible for the observed marked decrease in GAG content in the skin of diabetic rats and disturb the wound-healing process.


2020 ◽  
Vol 21 (8) ◽  
pp. 2678 ◽  
Author(s):  
Magnus S. Ågren ◽  
Ulrich auf dem Keller

Zinc-dependent matrix metalloproteinases (MMPs) belong to metzincins that comprise not only 23 human MMPs but also other metalloproteinases, such as 21 human ADAMs (a disintegrin and metalloproteinase domain) and 19 secreted ADAMTSs (a disintegrin and metalloproteinase thrombospondin domain). The many setbacks from the clinical trials of broad-spectrum MMP inhibitors for cancer indications in the late 1990s emphasized the extreme complexity of the participation of these proteolytic enzymes in biology. This editorial mini-review summarizes the Special Issue, which includes four review articles and 10 original articles that highlight the versatile roles of MMPs, ADAMs, and ADAMTSs, in normal physiology as well as in neoplastic and destructive processes in tissue. In addition, we briefly discuss the unambiguous involvement of MMPs in wound healing.


2011 ◽  
Vol 392 (11) ◽  
Author(s):  
Olivia Hermes ◽  
Pascal Schlage ◽  
Ulrich auf dem Keller

AbstractProteases are pivotal modulators of extracellular matrix components and bioactive proteins at all phases of cutaneous wound healing and thereby essentially contribute to the successful reestablishment of skin integrity upon injury. As a consequence, disturbance of proteolytic activity at the wound site is a major factor in the pathology of chronic wounds. A large body of data acquired in many years of research provide a good understanding of how individual proteases may influence the repair process. The next challenge will be to integrate these findings and to elucidate the complex interactions of proteolytic enzymes, their inhibitors and substrates on a system-wide level. Here, we present novel approaches that might help to achieve this ambitious goal in cutaneous wound healing research.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S192-S192
Author(s):  
Fatemeh Kalalinia ◽  
Nafise Aamiri ◽  
Samaneh Bayat ◽  
Jebrail Movaffagh ◽  
Maryam Hahsemi

Abstract Introduction Bromelain is a mixture of proteolytic enzymes present in all tissues of pineapple (Ananas comosus). It is known as an efficient debriding agent in burn treatment and has been shown to effectively and selectively debride burn eschar. In this study, the efficiency of bromelain-loaded chitosan nanofibers for burn wounds repair was investigated in animal model. Methods Chitosan nanofibers containing bromelain were prepared by electrospinning method. The physicochemical characteristics of the synthetized nanofibers, release profile and activity of bromelain loaded in nanofibers were evaluated. The burn healing effect of bromelain-loaded nanofibers were studied in the induced burn wounds in rats for 21 days. The efficacy of treatment was assessed by evaluating changes in wound closer and histological analysis at different time point. Results Successful electrospinning of bromelain-loaded chitosan nanofibers resulted in uniform and bead-less nanofibers which released bromelain up to 48h. The formulation kept bromelain enzyme activity after 6-month storage at 4 °C and did not show any cytotoxicity on human dermal fibroblasts. Moreover, in vivo study in a rat burn model confirmed the safety and efficacy of applying bromelain loaded nanofibers in burn wound healing when a significant improve in wound closer was observed in bromelain loaded group and histopathological studies showed more effects on re-epithelialization, debridement and more reduction of necrosis compared to chitosan alone. Conclusions Together, these results suggest that bromelain chitosan nanofiber possesses great wound healing activity and could be considered as an effective natural topical burn wound healing treatment.


2022 ◽  
Vol 12 ◽  
Author(s):  
Yuka Okada ◽  
Takayoshi Sumioka ◽  
Peter S. Reinach ◽  
Masayasu Miyajima ◽  
Shizuya Saika

The maintenance of normal vision is dependent on preserving corneal transparency. For this to occur, this tissue must remain avascular and its stromal architecture needs to be retained. Epithelial transparency is maintained provided the uppermost stratified layers of this tissue are composed of terminally differentiated non-keratinizing cells. In addition, it is essential that the underlying stromal connective tissue remains avascular and scar-free. Keratocytes are the source of fibroblasts that are interspersed within the collagenous framework and the extracellular matrix. In addition, there are sensory nerve fibers whose lineage is possibly either neural crest or mesenchymal. Corneal wound healing studies have been undertaken to delineate the underlying pathogenic responses that result in the development of opacification following chemical injury. An alkali burn is one type of injury that can result in severe and long- lasting losses in ocular transparency. During the subsequent wound healing process, numerous different proinflammatory cytokines and proteolytic enzymes undergo upregulation. Such increases in their expression levels induce maladaptive expression of sustained stromal inflammatory fibrosis, neovascularization, and losses in the smooth optical properties of the corneal outer surface. It is becoming apparent that different transient receptor potential channel (TRP) isoforms are important players in mediating these different events underlying the wound healing process since injury upregulates both their expression levels and functional involvement. In this review, we focus on the involvement of TRPV1, TRPA1 and TRPV4 in mediating some of the responses that underlie the control of anterior ocular tissue homeostasis under normal and pathological conditions. They are expressed on both different cell types throughout this tissue and also on corneal sensory nerve endings. Their roles have been extensively studied as sensors and transducers of environmental stimuli resulting from exposure to intrinsic modulators and extrinsic ligands. These triggers include alteration of the ambient temperature and mechanical stress, etc., that can induce pathophysiological responses underlying losses in tissue transparency activated by wound healing in mice losses in tissue transparency. In this article, experimental findings are reviewed about the role of injury-induced TRP channel activation in mediating inflammatory fibrotic responses during wound healing in mice.


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