Collagen-Derived Di-Peptide, Prolylhydroxyproline (Pro-Hyp): A New Low Molecular Weight Growth-Initiating Factor for Specific Fibroblasts Associated With Wound Healing

Many cells and soluble factors are involved in the wound healing process, which can be divided into inflammatory, proliferative, and remodeling phases. Fibroblasts play a crucial role in wound healing, especially during the proliferative phase, and show heterogeneity depending on lineage, tissue distribution, and extent of differentiation. Fibroblasts from tissue stem cells rather than from healthy tissues infiltrate wounds and proliferate. Some fibroblasts in the wound healing site express the mesenchymal stem cell marker, p75NTR. In the cell culture system, fibroblasts attached to collagen fibrils stop growing, even in the presence of protein growth factors, thus mimicking the quiescent nature of fibroblasts in healthy tissues. Fibroblasts in wound healing sites proliferate and are surrounded by collagen fibrils. These facts indicate presence of new growth-initiating factor for fibroblasts attached to collagen fibrils at the wound healing site, where the collagen-derived peptide, prolyl-hydroxyproline (Pro-Hyp), is generated. Pro-Hyp triggers the growth of p75NTR-positive fibroblasts cultured on collagen gel but not p75NTR-negative fibroblasts. Thus, Pro-Hyp is a low molecular weight growth-initiating factor for specific fibroblasts that is involved in the wound healing process. Pro-Hyp is also supplied to tissues by oral administration of gelatin or collagen hydrolysate. Thus, supplementation of gelatin or collagen hydrolysate has therapeutic potential for chronic wounds. Animal studies and human clinical trials have demonstrated that the ingestion of gelatin or collagen hydrolysate enhances the healing of pressure ulcers in animals and humans and improves delayed wound healing in diabetic animals. Therefore, the low molecular weight fibroblast growth-initiating factor, Pro-Hyp, plays a significant role in wound healing and has therapeutic potential for chronic wounds.

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Bioactive Agent-Loaded Electrospun Nanofiber Membranes for Accelerating Healing Process: A Review

Membranes ◽

10.3390/membranes11090702 ◽

2021 ◽

Vol 11 (9) ◽

pp. 702

Author(s):

Seyyed-Mojtaba Mousavi ◽

Zohre Mousavi Nejad ◽

Seyyed Alireza Hashemi ◽

Marjan Salari ◽

Ahmad Gholami ◽

...

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Therapeutic Potential ◽

Healing Process ◽

Wound Dressings ◽

Future Research ◽

Wound Healing Process ◽

Nanofiber Membranes ◽

Bioactive Agents ◽

Bioactive Agent

Despite the advances that have been achieved in developing wound dressings to date, wound healing still remains a challenge in the healthcare system. None of the wound dressings currently used clinically can mimic all the properties of normal and healthy skin. Electrospinning has gained remarkable attention in wound healing applications because of its excellent ability to form nanostructures similar to natural extracellular matrix (ECM). Electrospun dressing accelerates the wound healing process by transferring drugs or active agents to the wound site sooner. This review provides a concise overview of the recent developments in bioactive electrospun dressings, which are effective in treating acute and chronic wounds and can successfully heal the wound. We also discuss bioactive agents used to incorporate electrospun wound dressings to improve their therapeutic potential in wound healing. In addition, here we present commercial dressings loaded with bioactive agents with a comparison between their features and capabilities. Furthermore, we discuss challenges and promises and offer suggestions for future research on bioactive agent-loaded nanofiber membranes to guide future researchers in designing more effective dressing for wound healing and skin regeneration.

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In Vitro Evaluation of Novel Hybrid Cooperative Complexes in a Wound Healing Model: A Step Toward Improved Bioreparation

International Journal of Molecular Sciences ◽

10.3390/ijms20194727 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4727 ◽

Cited By ~ 4

Author(s):

Antonella D’Agostino ◽

Rosa Maritato ◽

Annalisa La Gatta ◽

Alessandra Fusco ◽

Sabrina Reale ◽

...

Keyword(s):

Molecular Weight ◽

Wound Healing ◽

Hyaluronic Acid ◽

Transforming Growth Factor ◽

Dermal Fibroblast ◽

Healing Process ◽

Wound Healing Process ◽

Low Molecular Weight ◽

Skin Wound Healing

The effectiveness of hyaluronic acid (HA), also called as hyaluronan, and its formulations on tissue regeneration and epidermal disease is well-documented. High-molecular-weight hyaluronan (HHA) is an efficient space filler that maintains hydration, serves as a substrate for proteoglycan assembly, and is involved in wound healing. Recently, an innovative hybrid cooperative complex (HCC) of high- and low-molecular-weight hyaluronan was developed that is effective in wound healing and bioremodeling. The HCC proposed here consisted of a new formulation and contained 1.6 ± 0.1 kDa HHA and 250 ± 7 kDa LHA (low molecular weight hyaluronic acid). We investigated the performance of this HCC in a novel in vitro HaCaT (immortalized human keratinocytes)/HDF (human dermal fibroblast) co-culture model to assess its ability to repair skin tissue lesions. Compared to linear HA samples, HCC reduced the biomarkers of inflammation (Transforming Growth Factor-β (TGF-β), Tumor Necrosis Factor receptor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8)), and accelerated the healing process. These data were confirmed by the modulation of metalloproteases (MMPs) and elastin, and were compatible with a prospectively reduced risk of scar formation. We also examined the expression of defensin-2, an antimicrobial peptide, in the presence of hyaluronan, showing a higher expression in the HCC-treated samples and suggesting a potential increase in antibacterial and immunomodulatory functions. Based on these in vitro data, the presence of HCC in creams or dressings would be expected to enhance the resolution of inflammation and accelerate the skin wound healing process.

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Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure

Pharmaceuticals ◽

10.3390/ph14040301 ◽

2021 ◽

Vol 14 (4) ◽

pp. 301

Author(s):

Yayoi Kawano ◽

Viorica Patrulea ◽

Emmanuelle Sublet ◽

Gerrit Borchard ◽

Takuya Iyoda ◽

...

Keyword(s):

Gene Expression ◽

Molecular Weight ◽

Wound Healing ◽

Hyaluronic Acid ◽

Healing Process ◽

Dermal Fibroblasts ◽

Water Soluble ◽

Wound Healing Process ◽

And Migration ◽

Proliferation And Migration

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.

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Polymer-Based Scaffolds Loaded with Aloe vera Extract for the Treatment of Wounds

Pharmaceutics ◽

10.3390/pharmaceutics13070961 ◽

2021 ◽

Vol 13 (7) ◽

pp. 961

Author(s):

Sibusiso Alven ◽

Vuyolwethu Khwaza ◽

Opeoluwa O. Oyedeji ◽

Blessing A. Aderibigbe

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Mechanical Performance ◽

Healing Process ◽

Aloe Vera ◽

Antimicrobial Properties ◽

Biological Properties ◽

Wound Management ◽

Wound Healing Process ◽

Treatment Of Wounds

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial properties, poor biodegradability and biocompatibility, and weak mechanical performance. Plant extracts, such as Aloe vera, have attracted significant attention in wound management because of their interesting biological properties. Aloe vera is composed of essential constituents beneficial for the wound healing process, such as amino acids, vitamins C and E, and zinc. Aloe vera influences numerous factors that are involved in wound healing and stimulates accelerated healing. This review reports the therapeutic outcomes of aloe vera extract-loaded polymer-based scaffolds in wound management.

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Identifying New Pathways and Targets for Wound Healing and Therapeutics from Natural Sources

Current Drug Delivery ◽

10.2174/1567201818666210111101257 ◽

2021 ◽

Vol 18 ◽

Author(s):

Xinchi Feng ◽

Jinsong Hao

Keyword(s):

Wound Healing ◽

Molecular Mechanisms ◽

Chronic Wounds ◽

Wound Care ◽

Healing Process ◽

Unmet Need ◽

Wound Dressings ◽

Wound Healing Process ◽

Natural Sources ◽

Viable Approach

: Chronic wounds remain a significant public problem and the development of wound treatments has been a research focus for the past few decades. Despite advances in the products derived from endogenous substances involved in a wound healing process (e.g. growth factors, stem cells, and extracellular matrix), effective and safe wound therapeutics are still limited. There is an unmet need to develop new therapeutics. Various new pathways and targets have been identified and could become a molecular target in designing novel wound agents. Importantly, many existing drugs that target these newly identified pathways could be repositioned for wound therapy, which will facilitate fast translation of research findings to clinical applications. This review discusses the newly identified pathways/targets and their potential uses in the development of wound therapeutics. Some herbs and amphibian skins have been traditionally used for wound repairs and their active ingredients have been found to act in these new pathways. Hence, screening these natural products for novel wound therapeutics remains a viable approach. The outcomes of wound care using natural wound therapeutics could be improved if we can better understand their cellular and molecular mechanisms and fabricate them in appropriate formulations, such as using novel wound dressings and nano-engineered materials. Therefore, we also provide an update on the advances in the wound therapeutics from natural sources. Overall, this review offers new insights into novel wound therapeutics.

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Functional Mining of the Crotalus Spp. Venom Protease Repertoire Reveals Potential for Chronic Wound Therapeutics

Molecules ◽

10.3390/molecules25153401 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3401

Author(s):

David Meléndez-Martínez ◽

Luis Fernando Plenge-Tellechea ◽

Ana Gatica-Colima ◽

Martha Sandra Cruz-Pérez ◽

José Manuel Aguilar-Yáñez ◽

...

Keyword(s):

Wound Healing ◽

Serine Proteases ◽

Chronic Wounds ◽

Chronic Wound ◽

Healing Process ◽

Wound Healing Process ◽

Major Health Problem ◽

Normal Wound Healing ◽

Alternative Sources ◽

Fibrin Clots

Chronic wounds are a major health problem that cause millions of dollars in expenses every year. Among all the treatments used, active wound treatments such as enzymatic treatments represent a cheaper and specific option with a fast growth category in the market. In particular, bacterial and plant proteases have been employed due to their homology to human proteases, which drive the normal wound healing process. However, the use of these proteases has demonstrated results with low reproducibility. Therefore, alternative sources of proteases such as snake venom have been proposed. Here, we performed a functional mining of proteases from rattlesnakes (Crotalus ornatus, C. molossus nigrescens, C. scutulatus, and C. atrox) due to their high protease predominance and similarity to native proteases. To characterize Crotalus spp. Proteases, we performed different protease assays to measure and confirm the presence of metalloproteases and serine proteases, such as the universal protease assay and zymography, using several substrates such as gelatin, casein, hemoglobin, L-TAME, fibrinogen, and fibrin. We found that all our venom extracts degraded casein, gelatin, L-TAME, fibrinogen, and fibrin, but not hemoglobin. Crotalus ornatus and C. m. nigrescens extracts were the most proteolytic venoms among the samples. Particularly, C. ornatus predominantly possessed low molecular weight proteases (P-I metalloproteases). Our results demonstrated the presence of metalloproteases capable of degrading gelatin (a collagen derivative) and fibrin clots, whereas serine proteases were capable of degrading fibrinogen-generating fibrin clots, mimicking thrombin activity. Moreover, we demonstrated that Crotalus spp. are a valuable source of proteases that can aid chronic wound-healing treatments.

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Bioactive and Bioadhesive Catechol Conjugated Polymers for Tissue Regeneration

Polymers ◽

10.3390/polym10070768 ◽

2018 ◽

Vol 10 (7) ◽

pp. 768 ◽

Cited By ~ 4

Author(s):

María Puertas-Bartolomé ◽

Blanca Vázquez-Lasa ◽

Julio San Román

Keyword(s):

Wound Healing ◽

Free Radicals ◽

Tissue Regeneration ◽

Chronic Wounds ◽

Healing Process ◽

Antioxidant Response ◽

Wound Healing Process ◽

Natural Polyphenol ◽

Moist Environment ◽

High Yields

The effective treatment of chronic wounds constitutes one of the most common worldwide healthcare problem due to the presence of high levels of proteases, free radicals and exudates in the wound, which constantly activate the inflammatory system, avoiding tissue regeneration. In this study, we describe a multifunctional bioactive and resorbable membrane with in-built antioxidant agent catechol for the continuous quenching of free radicals as well as to control inflammatory response, helping to promote the wound-healing process. This natural polyphenol (catechol) is the key molecule responsible for the mechanism of adhesion of mussels providing also the functionalized polymer with bioadhesion in the moist environment of the human body. To reach that goal, synthesized statistical copolymers of N-vinylcaprolactam (V) and 2-hydroxyethyl methacrylate (H) have been conjugated with catechol bearing hydrocaffeic acid (HCA) molecules with high yields. The system has demonstrated good biocompatibility, a sustained antioxidant response, an anti-inflammatory effect, an ultraviolet (UV) screen, and bioadhesion to porcine skin, all of these been key features in the wound-healing process. Therefore, these novel mussel-inspired materials have an enormous potential for application and can act very positively, favoring and promoting the healing effect in chronic wounds.

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Hydrogels for management of chronic wound healing

World Journal of Biology Pharmacy and Health Sciences ◽

10.30574/wjbphs.2021.5.3.0027 ◽

2021 ◽

Vol 5 (3) ◽

pp. 095-104

Author(s):

IM Cardoso-Daodu ◽

CP Azubuike ◽

MO Ilomuanya

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Healing Process ◽

Three Dimensional ◽

Scar Tissue ◽

The Body ◽

Polymer Chains ◽

Wound Healing Process ◽

Dimensional Network ◽

Healing Wound

Chronic wounds occur when one wound healing process or a sequence of wound healing events are affected resulting in slow healing of the wound thereby placing the patient in deep pain. Various diseases and conditions can delay the process of wound healing. Wound healing can be classified into four main stages: hemostasis, inflammation, remodeling, and scar tissue formation with each phase overlapping one another. The skin is the largest organ in the body. It protects the entire external surface of the human body and is the primary site of interaction with the outside environment. There is therefore a need to fabricate an ideal dressing through scientific research and investigations. Hydrogels are a three-dimensional network of hydrophilic polymers that can swell in water and absorb copious amounts of water while maintaining their structure because of their chemical or physical crosslinking of individual polymer chains. A hydrogel must be composed of at least 10% water. Hydrogels possess the flexibility and water percentage which is remarkably like tissues. They are biocompatible and biodegradable which makes them ideal for dermal wound healing.

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Hubungan Status Gizi dengan Proses Penyembuhan Luka pada Pasien Post Apendektomi

ARTERI : Jurnal Ilmu Kesehatan ◽

10.37148/arteri.v1i3.66 ◽

2020 ◽

Vol 1 (3) ◽

pp. 226-232

Author(s):

Andi Siswandi ◽

Mardheni Wulandari ◽

Mizar Erianto ◽

Azahrah Mawaddah Noviska

Keyword(s):

Wound Healing ◽

Nutritional Status ◽

Chronic Wounds ◽

Healing Process ◽

Wound Healing Process ◽

Chi Square ◽

Cross Sectional ◽

Surgical Infection ◽

Chi Square Test ◽

Acute Wound

Appendicitis is part of the emergency cases that often occur in the abdominal area. Appendicitis is a prototype disease that takes place through inflammation due to obstruction and ischemia with the main symptoms which is pain that reflects the state of the disease. Appendicitis requires surgical appendectomy to reduce the risk of perforation. Apendectomy surgery is one type of wound that is an incision wound. The time of wound healing can be determined by the distinguishing between types of acute or chronic wounds. Appendectomy that does not have a post-surgical infection is categorized as an acute wound, physiologically the acute wound will heal ± 0-21 days. However, if the provision of nutrition is not fulfilled properly it will be almost the wound healing process. One factor that can influence the wound healing process is nutritional status. This study aim to determine the correlation of nutritional status with the wound healing process of post-appendectomy patients in RSUD Dr. H. Abdoel Moeloek, Bandar Lampung. This study used observational analytic with cross sectional approach. The sampling technique used was accidental sampling. The data were analyzed by using Chi-square test. From the Chi-square test found a relationship of nutritional status with a significant wound healing process (p <0.05) which is obtained p = 0.004, and the value obtained (OR = 10.5) can be said that adequate nutritional status is 10.5 times more likely to experience good wound healing when compared to undernourished nutritional status. There is a correlation between nutritional status and wound healing process in post-appendectomy patients.

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Bionanomaterials: Advancements in Wound Healing and Tissue Regeneration

10.5772/intechopen.97298 ◽

2021 ◽

Author(s):

Priyanka Chhabra ◽

Kajol Bhati

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Wound Care ◽

Health Care Organization ◽

Healing Process ◽

Volume Ratio ◽

Wound Healing Process ◽

Care Organization ◽

Complex Process ◽

High Degree

Abnormal wound healing represents a major healthcare issue owing to upsurge number of trauma and morbid physiology which ultimately posed a healthcare burden on patient, society and health care organization. A wound healing is a complex process so effective management of chronic wounds is often hard. Recently in addition to many conventional wound treatment’s advances in bionanomaterial are attaining much attention in wound care and skin tissue engineering. Bionanomaterials are biomolecule-based nanocomposite synthesized by plants, microbes and animals which possess high degree of biocompatibility, biodegradability, non-toxicity and bioactive assets. Bioactive assets like antimicrobial, immune modulatory, cell proliferation and angiogenesis of biomolecules forms fortunate microenvironment for the wound healing process. Nature has provided us with a significant set of biomolecules like chitosan, hyaluronic acid, collagen, cellulose, silk fucoidan etc. have been exploited to construct engineered bionanomaterials. These biopolymeric nanomaterials are currently researched comprehensively as they have higher surface to volume ratio and high chemical affinity showing a promising augmentation of deadly wounds. In this chapter we aimed to highlight the biological sources and bioengineering approaches adapted for biopolymers so they facilitate wound healing process.

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