Normal Healing Process Research Articles

The functional and molecular impact of triamcinolone acetonide on primary human bone marrow mesenchymal stem cells

Traumatic or degenerative joint pain is abundant in the population. Symptom relief by intra- and periarticular glucocorticoid administration is frequently used, however may have potentially devastating effects, changing the normal healing process of the joint. Mesenchymal stem cells (MSCs) are important for wound-healing processes due to their multipotency in regenerating osteoblasts, chondrocytes and adipocytes but also have immunomodulatory properties. The aim of this study was to investigate the impact of triamcinolone acetonide (TA) a common glucocorticoid administrated intra- and periarticularly, on human bone marrow derived MSC viability, functionality, multi-lineage differentiation and transcriptomic output. We found that TA treatment induced apoptosis and promoted adipogenesis while impairing chondrogenesis of MSCs. RNA sequencing indicated that TA modulated the inflammatory response of MSCs, which may have an impact on the immunologic environment where the inflammatory phase is a physiological part of the natural healing process. These data indicate that triamcinolone acetonide should be used with consideration bearing the patient’s outcome in mind, with the intention to optimize joint recovery and homeostasis.

Successful rehabilitation after multiple severe complications following orthognathic surgery: a case report

BackgroundComplications of orthognathic surgery are quite rare, but they cause suffering in affected individuals. The range of complications is broad and includes both hard and soft tissue.Case presentationWe here present a case of a fully healthy woman without signs of impaired healing capacity. The patient underwent bimaxillary orthognathic surgery and experienced multiple complications both peri- and post-operatively. During the post operative period, the patient also suffered from soft tissue complications after an orthopaedic injury. Therefore, we referred the patient to her general practitioner for further medical investigation. We also present the result after restorative surgery and endodontic and prosthodontic treatment resulting in a successful rehabilitation.ConclusionThis case report clearly shows the need for a good collaboration between different odontological and medical fields to achieve a good and predictable result. In situations where normal healing processes do not occur, in-depth analysis must be carried out.HighlightsOrthognathic surgery affects soft and hard tissue which can result in adverse healing and complications. It is of great importance to follow up performed surgery to see late complications. Be restrictive with early re-operations when there are signs of necrosis. Always use a multidisciplinary approach when handling complications after surgery.

Zinc-mineralized diatom biosilica/hydroxybutyl chitosan composite hydrogel for diabetic chronic wound healing

For sustained and stable improvement of the diabetic wound microenvironment, a temperature-sensitive composite hydrogel (ZnDBs/HBC) composed of inorganic zinc mineralized diatom biosilica (ZnDBs) and hydroxybutyl chitosan (HBC) was developed. The interfacial anchoring effect between ZnDBs and HBC enhanced the mechanical strength of the hydrogel. The mechanical strength of the composite hydrogel containing 3 wt% ZnDBs was increased by nearly 2.3times. The hydrogel can be used as a carrier for sustained release of Zn2+ for at least 72 h. In diabetic rats models, ZnDBs/HBC composite hydrogel could accelerate the inflammatory process by regulating the expression of pro-inflammatory factor IL-6 and anti-inflammatory factor IL-10, and also promote tissue cell proliferation and collagen deposition, thereby restoring the normal healing process and accelerating wound healing. The wound contraction rate of the composite hydrogel group was more than 2 times that of the control group. Therefore, ZnDBs/HBC composite hydrogel has the potential to be used as a therapeutic dressing for diabetic chronic wounds.

Theruptor novo: wound dressing for diabetic foot ulcer

One of the main risk factor affecting the normal wound healing process of is diabetes. India being the capital for diabetes, has a prevalence of 9.6% with 74 million patients living with diabetes and is expected to be 124 million by 2045. The most dreadful complication of diabetes mellitus is the diabetic foot ulcer. Foot ulcer and amputation are among the leading reasons for high morbidity, healthcare costs and mortality in diabetes patients. Numerous things must come together for a chronic wound to heal, and one crucial component of care is the use of wound dressings and these should create an ideal environment for healing while safeguarding the site from infection and additional damage. A diabetic patient presented with a non-healing diabetic foot ulcer (10.83 cm2) with severe loss of protective sensation, exposed excised fourth and fifth metatarsals and he was treated and followed up with regular normal saline washes and Theruptor Novo dressings. The wound started to show signs of healing and within 7 weeks, the wound healed with complete epithelization. Theruptor Novo dressing was helpful in terms of good granulation tissue growth and epithe­lialization over time with good exudate management. Theruptor Novo, a non-adherent dressing with unique antimicrobial action cab be useful in managing diabetic foot ulcers.

Primed inflammatory response by fibroblast subset is necessary for proper oral and cutaneous wound healing.

Fibroblasts are ubiquitous mesenchymal cells that exhibit considerable molecular and functional heterogeneity. Besides maintaining stromal integrity, oral fibroblast subsets are thought to play an important role in host-microbe interaction during injury repair, which is not well explored in vivo. Here, we characterize a subset of fibroblast lineage labeled by paired-related homeobox-1 promoter activity (Prx1Cre+) in oral mucosa and skin and demonstrate these fibroblasts readily respond to microbial products to facilitate the normal wound healing process. Using a reporter mouse model, we determined that Prx1Cre+ fibroblasts had significantly higher expression of toll-like receptors 2 and 4 compared to other fibroblast populations. In addition, Prx1 immunopositive cells exhibited heightened activation of inflammatory transcription factor NF-κB during the early wound healing process. At the cytokine level, CXCL1 and CCL2 were significantly upregulated by Prx1Cre+ fibroblasts at baseline and upon LPS stimulation. Importantly, lineage-specific knockout to prevent NF-κB activation in Prx1Cre+ fibroblasts drastically impaired both oral and skin wound healing processes, which was linked to reduced macrophage infiltration, failure to resolve inflammation, and clearance of bacteria. Together, our data implicate a pro-healing role of Prx1-lineage fibroblasts by facilitating early macrophage recruitment and bacterial clearance.

Physiological and Pathophysiological Aspects of Diabetic Foot Ulcer and its Treatment Strategies.

Diabetes foot ulcers (DFU) are among the most common complications in diabetic patients, leading to amputation and psychological distress. This mini-review covers the general physiology of ulcer healing as well as the pathophysiology of DFU and its therapies. Only a few treatments have been sanctioned and numerous compounds from various pharmacological groups are now being tested at various stages for the prevention and treatment of DFUs. The main objective of this mini-review is to give concise information on how diabetes mellitus impairs the healing of chronic ulcers by disrupting numerous biological systems of the normal healing process, resulting in diabetic foot ulceration, and the current therapeutic approaches. A review of accessible material from systemic searches in the PubMed/Medline, Scopus, Cochrane Database of Systematic Reviews, published review articles, and Clinical Trials databases (US National Library of Medicine) with no period of limitation was conducted. The treatment of DFUs comprises wound dressings, use of matrix metalloproteinase inhibitors in wound dressing, antibiotics, skin substitutes, pressure off-loading growth factors and stem cells, gene therapy, topical oxygen therapy, etc. Conclusion: The majority of these treatments are aimed at treating diabetic foot ulcers and preventing diabetic wounds from becoming infected. Yet, there is no single therapy that can be advised for diabetic foot ulcer patients. Future treatment strategies should be considered an appropriate treatment option for persistent wounds.

The capacity of exosomes derived from adipose-derived stem cells to enhance wound healing in diabetes.

The slow healing and nonhealing of diabetic wounds have long posed challenges for clinical practitioners. In the presence of elevated glucose levels, the body's regulatory mechanisms undergo alterations that impede normal wound healing processes, including cell proliferation, cytokine release, and growth factor activity. Consequently, the advancement of stem cell technology has sparked growing interest in utilizing stem cells and their derivatives as potential therapeutic agents to enhance diabetic wound healing. This paper aims to provide an academic review of the therapeutic effects of adipose-derived stem cell-EXOs (ADSC-EXOs) in diabetic wound healing. As a cell-free therapy, exosomes (EXOs) possess a multitude of proteins and growth factors that have been shown to be advantageous in promoting wound healing and mitigating the potential risks associated with stem cell therapy. By examining the current knowledge on ADSC-EXOs, this review seeks to offer insights and guidance for the potential application of EXOs in the treatment of diabetic wounds.

Macrophage cell morphology-imprinted substrates can modulate mesenchymal stem cell behaviors and macrophage M1/M2 polarization for wound healing applications.

Mesenchymal stem cells and macrophages (MQ) are two very important cells involved in the normal wound healing process. It is well understood that topological cues and mechanical factors can lead to different responses in stem cells and MQ by influencing their shape, cytoskeleton proliferation, migration, and differentiation, which play an essential role in the success or failure of biomaterial implantation and more importantly wound healing. On the other hand, the polarization of MQ from proinflammatory (M1) to prohealing (M2) phenotypes has a critical role in the acceleration of wound healing. In this study, the morphology of different MQ subtypes (M0, M1, and M2) was imprinted on a silicon surface (polydimethylsiloxane [PDMS]) to prepare a nano-topography cell-imprinted substrate with the ability to induce anti-inflammatory effects on the mouse adipose-derived stem cells (ADSCs) and RAW264.7 monocyte cell line (MO). The gene expression profiles and flow cytometry of MQ revealed that the cell shape microstructure promoted the MQ phenotypes according to the specific shape of each pattern. The ELISA results were in agreement with the gene expression profiles. The ADSCs on the patterned PDMS exhibited remarkably different shapes from no-patterned PDMS. The MOs grown on M2 morphological patterns showed a significant increase in expression and section of anti-inflammatory cytokine compared with M0 and M1 patterns. The ADSCs homing in niches heavily deformed the cytoskeletal, which is probably why the gene expression and phenotype unexpectedly changed. In conclusion, wound dressings with M2 cell morphology-induced surfaces are suggested as excellent anti-inflammatory and antiscarring dressings.

Glycosaminoglycans: Roles in wound healing, formation of corneal constructs and synthetic corneas

Maintaining the clarity of the cornea is essential for vision, and is achieved through an exquisite array of collagen fibrils and proteoglycans in the corneal stroma. Alterations in the identity and modifications of the glycosaminoglycans (GAGs) are seen both throughout the normal wound healing process and in pathological conditions resulting in corneal opacity. Understanding these changes has been essential for the development of corneal prostheses and corneal reconstruction. The goal of this review article is to summarize and consolidate research in the alterations seen in glycosaminoglycans in injured and hypoxic states, address the role of proteins that can regulate glycosaminoglycans in the corneal wound healing process, and apply these findings to the context of corneal restoration through reconstruction or the insertion of synthetic devices.

A Detailed Review on Diabetic Wound Healing Activity

Skin damage is known as a wound. Hemostasis, inflammatory, proliferative, and tissue remodelling or resolution are the four perfectly timed and highly planned phases that make up the normal biological process of wound healing in the human body. There are two basic categories of wounds: acute wounds and chronic wounds. Long-term negative effects on one's health are caused by the chronic metabolic condition known as diabetes mellitus, which is becoming more common. 25 percent of those with diabetes mellitus are thought to have poor wound healing due to their diabetes. Oxygenation, infection, hormones related to ageing and sex, stress, diabetes, and obesity, drugs, alcoholism, smoking, and diet are among the factors that affect wound healing. To address their basic medical needs, According to estimates, 80% of people who live in underdeveloped nations need traditional medicines, which are typically made from medicinal plants. Numerous individuals in Africa and other poor nations employ using medicinal herbs to cure diabetic wounds and associated issues due to the abundant supply With therapeutic herbs and enough conventional wisdom regarding wounds healing. Recent developments in functional genomics, nanotechnology, wound healing in diabetics, along with a better knowing the pathophysiology of chronic wounds. In the following review, detailed information about healing of diabetic wounds with mechanism, factors affecting, impairment of wound healing with its pathophysiology, herbal treatments and current advances when treating diabetic wounds are examined.

Topical metformin accelerates wound healing by promoting collagen synthesis and inhibiting apoptosis in a diabetic wound model.

The wound healing process, which is a pathophysiological process that includes various phases, is interrupted in diabetes due to hyperglycemia, and since deterioration occurs in these phases, a normal healing process is not observed. The aim of the current study is to investigate the proliferative and antiapoptotic effects of metformin on wound healing after topical application on diabetic and non-diabetic wounds. For this purpose, we applied metformin topically on the full-thickness excisional wound model we created in diabetic and nondiabetic groups. We investigated the effects of metformin on the apoptotic index by the Terminal deoxynucleotidyl transferase mediated dUTP Nick-End Labeling method and on collagen-I, collagen-III, p53, and c-jun expression levels by quantitative reverse transcription polymerase chain reaction technique in wound biopsy tissues. Our results showed that c-jun and p53 mRNA levels and apoptotic index increased with the effect of diabetes, while collagen synthesis was disrupted. As a result of the study, we showed that metformin increases cellular proliferation and has anti-apoptotic effects by increasing collagen-I/III expression and decreasing p53/c-jun level, especially in diabetic wounds and also in normal wounds. In conclusion, the topical effect of metformin on diabetic wounds reversed the adverse effects caused by diabetes, increasing the wound healing rate and improving the wound repair process.

Study of plant-based cosmeceuticals and skin care

Skin is a great blockade that prevents the direct influence of external factors on the body and a variety of immunological responses keeps our skin in protection. Whenever skin is encountered with pathogens and wounds, inflammation response is triggered, which attracts the cells of immune system, enters the site and induce healing and repair. Though inflammation is a part of normal healing process, its over activation or prolonged duration damages skin and results in skin diseases from acne to cancer, based on the severity. It is evident that medicinal plants have played a significant part in people's lives all throughout the world in holistic healing and still do. Plant-based ingredients used in skin care products are safe for use in the sun since they protect the skin from sun damage, provide moisture and nourishment without causing sensitivity. This effort highlights the skin protection ability of natural compounds obtained from plants which were used for centuries in diverse parts of the world. The plant oils discussed in this review were extracted from the seeds of sea buckthorn, olive, coconut, grape, argan, almond, jojoba and leaves of aloe and lavender without which the skin care regimens will not be complete. The chemical composition, mode of use and experimental evidences that support skin care and curability of all the above listed plants were compiled and discoursed. These plants play a vital role in skin care products due to their lipid composition and antioxidant capabilities.

Oxygenated Wound Dressings for Hypoxia Mitigation and Enhanced Wound Healing.

Oxygen is a critical factor that can regulate the wound healing processes such as skin cell proliferation, granulation, re-epithelialization, angiogenesis, and tissue regeneration. However, hypoxia, a common occurrence in the wound bed, can impede normal healing processes. To enhance wound healing, oxygenation strategies that could effectively increase wound oxygen levels are effective. The present review summarizes wound healing stages and the role of hypoxia in wound healing and overviews current strategies to incorporate various oxygen delivery or generating materials for wound dressing, including catalase, nanoenzyme, hemoglobin, calcium peroxide, or perfluorocarbon-based materials, in addition to photosynthetic bacteria and hyperbaric oxygen therapy. Mechanism of action, oxygenation efficacy, and potential benefits and drawbacks of these dressings are also discussed. We conclude by highlighting the importance of design optimization in wound dressings to address the clinical needs to improve clinical outcomes.

Combined Growth Factor Hydrogel Enhances Rotator Cuff Enthesis Healing in Rat But Not Sheep Model.

We hypothesized that a combined growth factor hydrogel would improve chronic rotator cuff tear healing in a rat and sheep model. Insulin-like growth factor 1, transforming growth factor β1, and parathyroid hormone were combined into a tyraminated poly-vinyl-alcohol (PVA-Tyr) hydrogel and applied directly at the enthesis. In total, 30 Sprague-Dawley rats and 16 Romney ewes underwent unilateral rotator cuff tenotomy and then delayed repairs were performed after 3-4 weeks. The animals were divided into a control group (repair alone) and treatment group. The rotator cuffs were harvested at 12 weeks after surgery for biomechanical and histological analyses of the repair site. In the rat model, the stress at failure and Young's modulus were higher in the treatment group in comparison with the control group (73% improvement, p = 0.010 and 56% improvement, p = 0.028, respectively). Histologically, the repaired entheses in the treatment group demonstrated improved healing with higher semi-quantitative scores (10.1 vs. 6.55 of 15, p = 0.032). In the large animal model, there was no observable treatment effect. This PVA-Tyr bound growth factor system holds promise for improving rotator cuff healing. However, our approach was not scalable from a small to a large animal model. Further tailoring of this growth factor delivery system is still required. Level of Evidence: Basic Science Study; Biomechanics and Histology; Animal Model Impact Statement Previous studies using single-growth factor treatment to improve enthesis healing after rotator cuff repair have reported promising, but inconsistent results. A novel approach is to combine multiple growth factors using controlled-release hydrogels that mimic the normal healing process. In this study, we report that a combined growth factor hydrogel can improve the histological quality and strength of rotator cuff repair in a rat chronic tear model. This novel hydrogel growth factor treatment has the potential to be used in human clinical applications to improve healing after rotator cuff repair.

Balloon Flower Root-Derived Extracellular Vesicles: In Vitro Assessment of Anti-Inflammatory, Proliferative, and Antioxidant Effects for Chronic Wound Healing.

Excessive reactive oxygen species (ROS) in wound lesions can lead to oxidative stress and failure of normal wound healing processes, eventually resulting in chronic skin wounds. A multitude of researchers have investigated various natural products with physiological activities, including antioxidant effects, for healing chronic skin wounds. Balloon flower root (BFR), which contains bioactive components such as platycodins, is known for its anti-inflammatory and antioxidant effects. In this study, we isolated BFR-derived extracellular vesicles (BFR-EVs) that possess anti-inflammatory, proliferative, and antioxidant activities via a combination of polyethylene glycol-based precipitation and ultracentrifugation. Our objective was to investigate the potential of BFR-EVs in treating chronic wounds caused by ROS. Despite efficient intracellular delivery, BFR-EVs showed no significant cytotoxicity. In addition, BFR-EVs inhibited the expression of pro-inflammatory cytokine genes in lipopolysaccharide-stimulated RAW 264.7 cells. Furthermore, water-soluble tetrazolium salt-8 assay showed that BFR-EVs had a proliferation-promoting effect on human dermal fibroblasts (HDFs). Scratch closure and transwell migration assays indicated that BFR-EVs could promote the migration of HDFs. When the antioxidant effect of BFR-EVs was evaluated through 2',7'-dichlorodihydrofluorescein diacetate staining and quantitative real-time polymerase chain reaction, the results revealed that BFR-EVs significantly suppressed ROS generation and oxidative stress induced by H2O2 and ultraviolet irradiation. Our findings suggest that BFR-EVs hold the potential as a natural candidate for healing chronic skin wounds.

COOLED BOILED WATER VERSUS STERILE NORMAL SALINE IN WOUND CLEANSING, A RANDOMIZED CONTROLLED TRIAL

Introduction: Wound cleansing plays a vital role in wound management. Although various solutions have been recommended for cleansing wounds, normal saline is favoured as it is an isotonic solution and is not thought to interfere with the normal healing process. Cooled boiled water is commonly used in community settings for cleansing wounds because it is easily accessible, efcient and cost-effective; however, there is an unresolved debate about its use. The aim of the study was to test whether there are differences in wound infection and w Aims And Objectives: ound healing rates when wounds are irrigated with cooled boiled water compared to sterile normal saline. Can this approach be used in a community environment without risk? Subjects were randomly assigned to wound cleansing with cooled Method: boiled water (experimental group) or sterile normal saline (control group). Wound assessment was conducted at each hospital visit, and an assessment of wound size was conducted once a week. The main outcome measures, occurrence of a wound infection and wound healing, were assessed over a period of 6 weeks. Study ndings indicate that cooled b Conclusion: oiled water is a safe alternative to sterile normal saline for wound cleansing and this method can be safely applied to community setting.

Utilization of ActiGraft an Autologous Whole Blood Clot for Treatment of Complex Wounds Linked to Comorbidities

Delayed wound healing can be attributed to the patient’s comorbidities, having a negative effect on the body’s normal wound healing process. While the normal healing process goes through four phases, the chronic wound is not progressing from the inflammatory phase, with constant destruction of the extracellular matrix (ECM), not allowing a scaffold to cover the wound and protect it from bacteria bioburden.

Endoscopic observation of pharyngeal mucosal suture healing process after total laryngectomy: case series

Background Pharyngocutaneous fistula (PCF), a major complication of total laryngectomy, is caused by pharyngeal repair failure. Objective Assess the usefulness of endoscopic observation of the pharyngeal suture’s healing process for the early detection of PCF development. Methods Pharyngeal mucosal sutures were endoscopically observed postoperatively in patients who underwent total laryngectomy with primary closure. Results Postoperatively, a white coat adhered to the pharyngeal mucosal suture of all patients. In most cases, the white coat gradually receded, which was considered to be a normal healing process. Thickening of the white coat and/or dehiscence of surgical wound were interpreted as ‘poor healing conditions’. Three cases were judged to have developed poor healing conditions of the pharyngeal mucosal suture and one patient developed PCF. The other two patients did not develop PCF, possibly due to early detection of ‘poor healing condition’ and conservative approach, such as discontinuation of oral intake. Conclusions Postoperative poor healing conditions of the pharyngeal mucosal suture may be precursors to PCF development. Endoscopic observation enables early detection of these conditions and may enable the prevention of PCF.

Assessment of functional and radiological outcomes of closed reduction and K-wire fixation of supracondylar fracture of humerus in children

: Supracondylar fractures of the humerus are commonly seen in children and are difficult to manage because of their unstable nature. It is difficult to maintain the reduction with splints. Non-operative treatment is associated with malunion and open reduction is more invasive procedure. Closed reduction of the fracture with percutaneous K-wire fixation is the preferred procedure with satisfactory results. : Children who came to the tertiary care hospital with a fracture in the supracondylar region following history of trauma to the elbow region and X-ray showing Gartland Type II and extension Type III fractures were included in this study. All these fractures were managed with closed reduction and fixation with K-wires inserted by percutaneous technique. Functional outcome and radiological union were noted.: A total of 35 children were operated. About half of the study population were in the range of 6 to 8 years. Majority of study subjects were boys. The average time period between sustaining a fracture and surgical procedure was 1.35 ± 0.48 days. The final results of this treatment modality were graded based on Flynn’s criteria and about 94.28% of study subjects had excellent to good outcomes. One child had complication of superficial pin tract infection.: Displaced supracondylar fractures of humerus can be effectively managed with closed reduction and percutaneous criss-cross K-wire fixation. This procedure does not disturb the normal fracture healing process.

The Clinical Profile of Patients with Chronic Wounds at Dr. Soetomo General Hospital 2015-2020

Background: Wounds that have lasted a long time due to failure to continue the normal healing process can be called chronic wounds. Chronic wounds occur due to multiple factors. There are problems that are often found in chronic wounds, such as the presence of exudate, necrotic tissue, and bacteria. The incidence of chronic wounds is closely related to the high cost of treatment and impaired quality of life. Prompt wound management is needed to optimize wound healing. Purpose: To determine the profile of chronic wounds in patients treated by the Department of Plastic Surgery Dr. Soetomo General Hospital Surabaya from 2015 – 2020. Methods: The data were obtained from patients medical records through total sampling technique, which consist of age, gender, past medical history, clinical features, diagnosis, management, and outcome. Result: This study involved 53 patients, dominated by male patients (70%) aged 46-65 years old (34%). The patient’s history showed that most patients suffered from type 2 diabetes (22%). The problem that often occurs is the presence of exudate which is mostly diagnosed with pressure ulcers (40%). All patient get wound bed preparation and the patient's outcome was dominated by recovery (72%). Conclusion: There are several factors affecting wound healing and prompt wound management are important to improving the outcomes.