Natural Wound Healing Process Research Articles

Instant clot forming and antibacterial wound dressings: Achieving hemostasis in trauma injuries with S-nitroso-N-acetylpenicillamine-tranexamic acid-propolis formulation.

Wound infection and excessive blood loss are the two major challenges associated with trauma injuries that account for 10% of annual deaths in the United States. Nitric oxide (NO) is a gasotransmitter cell signaling molecule that plays a crucial role in the natural wound healing process due to its antibacterial, anti-inflammatory, cell proliferation, and tissue remodeling abilities. Tranexamic acid (TXA), a prothrombotic agent, has been used topically and systemically to control blood loss in reported cases of epistaxis and combat-related trauma injuries. Its properties could be incorporated in wound dressings to induce immediate clot formation, which is a key factor in controlling excessive blood loss. This study introduces a novel, instant clot-forming NO-releasing dressing, and fabricated using a strategic bi-layer configuration. The layer adjacent to the wound was designed with TXA suspended on a resinous bed of propolis, which is a natural bioadhesive possessing antibacterial and anti-inflammatory properties. The base layer, located furthest away from the wound, has an NO donor, S-nitroso-N-acetylpenicillamine (SNAP), embedded in a polymeric bed of Carbosil®, a copolymer of polycarbonate urethane and silicone. Propolis was integrated with a uniform layer of TXA in variable concentrations: 2.5, 5.0, and 7.5 vol % of propolis. This design of the TXA-SNAP-propolis (T-SP) wound dressing allows TXA to form a more stable clot by preventing the lysis of fibrin. The lactate dehydrogenase-based platelet adhesion assay showed an increase in fibrin activation with 7.5% T-SP as compared with control within the first 15 min of its application. A scanning electron microscope (SEM) confirmed the presence of a dense fibrin network stabilizing the clot for fabricated dressing. The antibacterial activity of NO and propolis resulted in a 98.9 ± 1% and 99.4 ± 1% reduction in the colony-forming unit of Staphylococcus aureus and multidrug-resistant Acinetobacter baumannii, respectively, which puts forward the fabricated dressing as an emergency first aid for traumatic injuries, preventing excessive blood loss and soil-borne infections.

Gelatin-based biomaterials and gelatin as an additive for chronic wound repair.

Disturbing or disrupting the regular healing process of a skin wound may result in its progression to a chronic state. Chronic wounds often lead to increased infection because of their long healing time, malnutrition, and insufficient oxygen flow, subsequently affecting wound progression. Gelatin-the main structure of natural collagen-is widely used in biomedical fields because of its low cost, wide availability, biocompatibility, and degradability. However, gelatin may exhibit diverse tailored physical properties and poor antibacterial activity. Research on gelatin-based biomaterials has identified the challenges of improving gelatin's poor antibacterial properties and low mechanical properties. In chronic wounds, gelatin-based biomaterials can promote wound hemostasis, enhance peri-wound antibacterial and anti-inflammatory properties, and promote vascular and epithelial cell regeneration. In this article, we first introduce the natural process of wound healing. Second, we present the role of gelatin-based biomaterials and gelatin as an additive in wound healing. Finally, we present the future implications of gelatin-based biomaterials.

Topical gel preparation from Staphylococcus epidermidis isolate extract accelerated healing on incision wound model in rats

A wound is a disorder of skin integrity caused by physical trauma or disease. Wound healing is a natural restorative response to tissue injury. It is a complex dynamic physiological process involving several overlapping phases. Although wound management has been applied, however, some time it is associated withmajor drawbak including invasiveness, antibiotic resistance, and high costs. Natural medicines are being developed for wound management to resolve the drawback. Commensal Staphylococcus epidermidis was proven to play a role in natural wound healing process. This study aimed to investigate the wound healingactivity of a topical gel preparation containing S. epidermidis isolate extract on an incision wound model in rats. The methanol extract of S. epidermidis isolate was prepared by maceration and used as an active ingredient of the topical gel using NaCMC as a gelling agent. A physical stability test was carried out by assessingorganoleptic properties, pH value, homogeneity, dispersion, and viscosity of the gel preparation. The gel preparation was then topically applied once-daily for 11 d on incision wound model of male white rats (Rattus norvegicus). The wound healing was observed daily and calculated using Morton’s formula. Nosignificant change in the physical stability parameters of the gel preparation was observed during observation on day 1, 7, and 14 (p>0.05). A significant increase in wound healing after the application of the gel preparation compared to negative control was observed (p<0.05). In contrast, no significant difference inwound healing between the gel preparation and the positive control group was observed (p>0.05). In conclusion, the topical gel preparation from S. epidermidis isolate extract accelerates healing on incision wound models in rats.

Collagen-Based Scaffolds for Chronic Skin Wound Treatment.

Chronic wounds, commonly known as ulcers, represent a significant challenge to public health, impacting millions of individuals every year and imposing a significant financial burden on the global health system. Chronic wounds result from the interruption of the natural wound-healing process due to internal and/or external factors, resulting in slow or nonexistent recovery. Conventional medical approaches are often inadequate to deal with chronic wounds, necessitating the exploration of new methods to facilitate rapid and effective healing. In recent years, regenerative medicine and tissue engineering have emerged as promising avenues to encourage tissue regeneration. These approaches aim to achieve anatomical and functional restoration of the affected area through polymeric components, such as scaffolds or hydrogels. This review explores collagen-based biomaterials as potential therapeutic interventions for skin chronic wounds, specifically focusing on infective and diabetic ulcers. Hence, the different approaches described are classified on an action-mechanism basis. Understanding the issues preventing chronic wound healing and identifying effective therapeutic alternatives could indicate the best way to optimize therapeutic units and to promote more direct and efficient healing.

Regenerative potential of mesenchymal stromal cells in wound healing: unveiling the influence of normoxic and hypoxic environments.

The innate and adaptive immune systems rely on the skin for various purposes, serving as the primary defense against harmful environmental elements. However, skin lesions may lead to undesirable consequences such as scarring, accelerated skin aging, functional impairment, and psychological effects over time. The rising popularity of mesenchymal stromal cells (MSCs) for skin wound treatment is due to their potential as a promising therapeutic option. MSCs offer advantages in terms of differentiation capacity, accessibility, low immunogenicity, and their central role in natural wound-healing processes. To accelerate the healing process, MSCs promote cell migration, angiogenesis, epithelialization, and granulation tissue development. Oxygen plays a critical role in the formation and expansion of mammalian cells. The term "normoxia" refers to the usual oxygen levels, defined at 20.21 percent oxygen (160 mm of mercury), while "hypoxia" denotes oxygen levels of 2.91 percent or less. Notably, the ambient O2 content (20%) in the lab significantly differs from the 2%-9% O2 concentration in their natural habitat. Oxygen regulation of hypoxia-inducible factor-1 (HIF-1) mediated expression of multiple genes plays a crucial role in sustaining stem cell destiny concerning proliferation and differentiation. This study aims to elucidate the impact of normoxia and hypoxia on MSC biology and draw comparisons between the two. The findings suggest that expanding MSC-based regenerative treatments in a hypoxic environment can enhance their growth kinetics, genetic stability, and expression of chemokine receptors, ultimately increasing their effectiveness.

GEL EXTRACTION OF EARTHWORMS (Lumbricus rubellus) TO THE NUMBER OF FIBROBAL CELLS IN MALE WISTAR RATS (Rattus norvegiccus) GINGIVAL WOUND HEALING

Introduction: Gingiva is one of the oral mucosa that is most susceptible to injury, one of the factors is surgical procedures such as curettage which will be followed by a natural wound healing process. When a wound occurs, the cells that act as the building blocks of ground substance and the formation of collagen fibers in closing the wound are fibroblast cells. Many people think of earthworms (Lumbricus rubellus) only as animal feed or fish feed, but earthworms have many properties in antiperetic, antispasmodic, antidiuretic, antiasmatic, antihypertensive, antiallergic, anti-inflammatory, and have fibrinolytic activity. The purpose of this study was to determine the effect of the application of earthworm (Lumbricus rubellus) extract gel on the number of fibroblast cells in the gingival wound healing process of male Wistar (Rattus norvegicus) rats. Materials and Methods : This research method used in vivo laboratory experiments on wistar rats with three treatment groups, namely the group receiving 80% earthworm extract gel, and the control group giving placebo gel (CMC-Na 2%) which was observed on day 3. Results and Discussion: The results showed that there was a significant difference in the mean score of the number of fibroblasts on day 3 in the treatment group and the control group. The treatment group was given an 80% concentration of earthworm (Lumbricus rubellus) extract gel, which was 418.67, while the control group on day 3 was 270.33. Conclusion: It can be concluded that the gel extract of earthworm (Lumbricus rubellus) concentrate 80% is effective in increasing the number of fibroblast cells in the healing process of rat gingival wounds.

Reconstruction of large volume breast excision area with volume replacement after using V mammoplasty technique

The main goal in breast cancer surgery should be to perform safe surgery within the framework of oncological principles and to achieve the ideal cosmetic appearance that will not impair the person's quality of life. With this aspect, oncoplastic breast cancer surgery, which was developed for the solution of situations where classical breast-conserving surgery methods are insufficient, is being applied at increasing rates today. The cosmetic success of breast-conserving surgery can be understood after radiotherapy is given. The tissue gap formed in a lumpectomy is closed by the organization of the tissue fluid accumulated in the excision area over time. Fibrosis, which will develop during the natural wound-healing process, increases significantly after radiotherapy and may cause a change in appearance. In oncoplastic techniques, the defect is closed primarily by shifting the breast tissue, thus preserving the cosmetic.
 As an example, our study aimed to present the V mammoplasty technique applied to a premenopausal patient in the fourth decade with atypical ductal hyperplasia covering the entire inner half of one breast, with moderate ptosis and macromastia. 
 Today, breast cancer is accepted as a chronic disease and multidisciplinary teamwork is required for effective treatment. General surgeons play an important role in this team in terms of the interventional treatment of the disease and the preservation of the patient's quality of life. For this purpose, it is necessary for them to know and be able to apply most of the low and high-difficulty levels of oncoplastic techniques.

Biocide loaded shear-thinning hydrogel with anti-biofilm efficacy cures topical infection.

The continuous intervention of multidrug-resistant (MDR) bacterial infections worsens and slows the dynamicity of natural wound healing processes. Fortunately, antibiotics, metal ions, or metal nanoparticle-loaded antimicrobial hydrogels have been developed to tackle infections at injury sites and speed up the healing process. Despite their success, these marketed released based hydrogels are still limited owing to their lack of broad-spectrum activity, inability to tackle biofilm-associated infections, susceptibility towards resistance development, fast release kinetics, and mild to moderate toxicity. To address these shortcomings, we report the development of a biocompatible, shear-thinning, injectable gellan-gelatin hydrogel loaded with a peptidomimetic potent biocide (ASAM-10). The hydrogel upon sustained biocide release (60% within 72 h), displays a broad-spectrum antibacterial activity with negligible in vitro (hemolysis < 20%) and in vivo toxicity (no adverse effects on dermal layer of mice). Besides tackling bacterial dormant subpopulation (1-6 Log reduction), the optimized hydrogel is able to disrupt the preformed bacterial biofilm and even kill the biofilm-trapped pathogens with enhanced pathogenicity. Above all, the lead hydrogel was proficient in tackling methicillin-resistant Staphylococcus aureus (MRSA) wound infections in a mouse model through its safe topical administration. Overall, the biocide-loaded hydrogel can be considered as a promising candidate to combat MDR chronic infections at the wound site.

Developing novel plant waste-based hydrogels for skin regeneration and infection detection in diabetic wounds

More than 70,000 diabetic patients have amputations annually due to wound care complications. Poor circulation and hyperglycemia-related nerve damage, which are complications of diabetes, prevent natural wound-healing processes. The purpose of this investigation is to develop a hydrogel to aid skin regeneration by creating an extracellular matrix for fibroblast growth with antibacterial and infection-detection properties. We developed two natural hydrogels based on pectin and potato peels and characterized the gels for fibroblast compatibility through rheology, scanning electron microscopy, swelling, degradation, and cell cytotoxicity assays. All five assays indicated that potato peel starch and citrus pectin were capable of mimicking natural skin, with a relevant pore diameter and stiffness. Both groups were able to absorb 40 times their weight before naturally degrading and supported upwards of 500% NIH 3T3 fibroblast proliferation. Additionally, anthocyanin, a pigmented flavonoid, was encapsulated in hydrogels and used as an infection biomarker and preventative agent. We conducted a pH responsivity test and time-to-kill antibacterial assay, validating the ability of anthocyanin to noticeably change colors in hydrogels and assert bactericidal effects even at low concentrations. A concentration of 200 milligrams could prevent bacteria growth and showed no effect on fibroblast growth. Overall, this experiment fabricated various hydrogels capable of acting as skin substitutes and counteracting infections to facilitate wound healing. Following further testing and validation, these hydrogels could help alleviate the 13-billion-dollar financial burden of foot ulcer treatment.

Evaluation of clinical and histological effects of KGF-2 and NGF on corneal wound healing in an experimental alkali burn rabbit model

Endogenously produced peptide growth factors such as keratinocyte growth factor-2 (KGF-2) and nerve growth factor (NGF) play a key role in the natural corneal wound healing process. However, this self-healing ability of the corneal tissue is often impaired in cases of severe corneal damage, as in corneal alkali injuries. In the present study, we investigated the clinical and histopathological effects of topical recombinant human keratinocyte growth factor-2 and nerve growth factor treatments in a rabbit model of corneal alkali burn. After induction of an alkali burn, 24 rabbits were divided equally into three groups: control group, KGF-2 group, and NGF group. Clinical parameters including epithelial healing, opacification, neovascularization and central corneal thickness were evaluated on the first (D1), seventh (D7) and fourteenth (D14) days after injury. Corneal histology was performed using hematoxylin/eosin (H&E) and Masson's Trichrome stains. Immunohistochemical staining for matrix metalloproteinase-2 (MMP-2), MMP-9 and transforming growth factor-β (TGF-β) was performed. On D14, the percentage of epithelial defect and opacity were significantly less in the KGF-2 and NGF groups compared to the control group (p < 0.05). There was no significant difference between the groups in central corneal thickness. In the evaluation of neovascularization on D14, the NGF group was significantly less vascularized than the control group (p = 0.011). Histological examination showed a significant increase in stromal edema and inflammation in the control group compared to both treatment groups (p < 0.05). There was also a significant difference between the NGF and control groups in histological evaluation of epithelial repair and vascularization (p < 0.05). When immunoreactivity of MMP-2, MMP-9 and TGF-β was examined, there was a significant increase in the control group compared to the NGF group (p < 0.05). Taken together, both NGF and KGF-2 treatments were effective for early re-epithelialization and decrease in inflammation, opacity and neovascularization after corneal alkali burn. The inhibitory effect of NGF treatment on chemical-induced neovascularization was found to be superior to KGF-2 treatment.

In vivo study of beta-glucan-based biogenic synthesis of silver nanocomposite using Schizophyllum commune for wound dressings in a rat burn model

Bacterial infection is a significant barrier to the natural wound healing process. Silver nanoparticles have antibacterial activity through the destruction of DNA and bacterial membranes. In the present study, a green method was introduced to synthesize silver nanoparticles produced by the Schizophyllum commune. The antibacterial mat loaded with 0.5, 1, and 3% (w/w) of bioactive silver nanoparticles were produced in polyvinyl alcohol (PVA) and schizophyllan (SPG) solution (20:80) with electrospun (PVA/SPG). Then the physicochemical properties of silver nanoparticles and the mats PVA/SPG containing silver nanoparticles were investigated. An animal model also examined antimicrobial activity, cytotoxicity, adhesion, and grade II burn ulcers. The results showed that spherical silver nanoparticles with a diameter of about 40 nm were produced and completely scattered on the nanofibers according to TEM images. A non-covalent interaction was revealed between SPG and AgNPs; the nanofibers were hydrophilic. Nanofibers containing silver nanoparticles had intense antimicrobial activity against E. coli and S. aureus. This inhibition increases with increasing concentration. The cytotoxicity and adhesion results showed that the PVA/SPG-AgNPs 1% sample had the best effect on fibroblast cells. The 1% sample was tested for the animal model, and after 14 days, it had a practical effect on the control. At 14 days post-treatment, a skinny epithelial layer was formed and covered the wound area, and these nanofibers were suitable for wound dressing. Consequently, PVA/SPG-AgNPs nanofibers could be a good option to cover burn wounds by speeding up the wound healing process and treatment costs.

Local wound management: A review of modern techniques and products.

Management of wounds is a commonly performed and essential aspect of small animal veterinary medicine. Appropriate wound management is a difficult art to master, due to the inherent complexity of the clinical scenario, as well as the ever-evolving nature of the field with the constant addition of new products and techniques. This article reviews key concepts that may help the practitioner better understand the natural process of wound healing, factors that delay healing and strategies to help improve the local wound environment to make it more conducive to healing during open wound management. The concept of wound bed preparation is defined before common local wound management strategies, such as wound lavage and debridement, are discussed in more detail. Key aspects of the management of biofilms and appropriate use of antimicrobial agents are also reviewed. Finally, the concept of moist wound healing and its impact in modern wound management is explained before a broad variety of types of wound dressings are reviewed, with a particular focus on active dressings.

Photobiomodulation Therapy through a Novel Flat-Top Hand-Piece Prototype Improves Tissue Regeneration in Amphioxus (Branchiostoma lanceolatum): Proposal of an Ethical Model for Preclinical Screening

Despite the literature providing compelling evidence for the medical efficacy of photobiomodulation (PBM) therapy, its consistency in terms of accuracy and standardization needs improving. Identification of new technology and reliable and ethical biological models is, therefore, a challenge for researchers working on PBM. We tested the reliability of PBM irradiation through a novel delivery probe with a flat-top beam profile on the regenerating amphioxus Branchiostoma lanceolatum. The caudalmost 9 ± 1 myotomes, posterior to the anus, were excised using a sterile lancet. Animals were randomly split into three experimental groups. In the control group, the beam area was bounded with the 635-nm red-light pointer (negligible power, &lt;0.5 mW) and the laser device was coded to irradiate 810 nm and 0 W. In Group laser-1, the beam area was bounded with the same 635-nm red-light pointer and irradiated at 810 nm, 1 W in CW for 60 s, spot-size 1 cm2, 1 W/cm2, 60 J/cm2, and 60 J; irradiation was performed every day for two weeks. In Group laser-2, the beam area was bounded with the same 635-nm red-light pointer and irradiated at 810 nm, 1 W in CW for 60 s, spot-size 1 cm2, 1 W/cm2, 60 J/cm2, and 60 J; irradiation was performed on alternate days for four weeks. We observed that PBM improved the natural wound-healing and regeneration process. The effect was particularly evident for the notochord. Daily irradiation better supported the regenerative process.

An Overview on the Recent Advances in the Treatment of Infected Wounds: Antibacterial Wound Dressings.

A wound can be surgical cuts from an operation or due to accident and trauma. The infected wound, as a result of bacteria growth within the damaged skin, interrupts the natural wound healing process and significantly impacts the quality of life. Wound dressing is an important segment of the skincare industry with its economic burden estimated at $ 20.4 billion (in 2021) in the global market. The results of recent clinical trials suggest that the use of modern dressings can be the easiest, most accessible, and most cost-effective way to treat chronic wounds and, hence, holds significant promise. With the sheer number of dressings in the market, the selection of correct dressing is confusing for clinicians and healthcare workers. The aim of this research is to review widely used types of antibacterial wound dressings, as well as emerging products, for their efficiency and mode of action. In this review, introducing antibiotics and antibacterial nanoparticles as two important and clinically widely used categories of antibacterial agents is focused. The perspectives and challenges for paving the way for future research in this field are also discussed.

Chronic venus ulcer pain reduction and full recovery by an autologous blood clot: A case study

Introduction: Venous Leg Ulcers (VLU) can be associated with severe pain, having a tremendous effect on the ulcer treatment and eventually the patient’s quality of life. Dressing removal and procedures are the main cause for VLU pain, however, background pain is common in chronic wounds, with numerous patients needing analgesics to manage the pain. ActiGraft is an autologous whole blood clot, created by the patient’s own peripheral blood, at a point of care to treat cutaneous wounds. ActiGraft mimics the Extracellular Matrix (ECM) by creating a protective scaffold, that promotes the acceleration of the wound healing process. Case study: We here by describe a case study of a 63-year-old patient who exhibits a 1-year-old VLU, that went under advanced treatments previously with no improvement. This was the result of the deterioration of a simple scratch that extended to a spreading wound, covering a large area of the shin. The patient experienced high pain levels and consumed large amounts of analgesics during the past year of his life, with no significant relief. The patient suffered severe pain and was unable to sleep for more than a 3 hour period, every single night. ActiGraft weekly application was able to change the pain form during the first treatment and followingly reduce the pain levels with a constant decrease in wound pain with every application. ActiGraft treatment was able to promote the healing process, achieving a complete wound healing after receiving 16 weeks of constant treatment. Discussion: Pain associated with VLU has a major effect on the patient’s quality of life and can significantly impact the ability to efficiently treat the ulcer. ActiGraft treatment progressed the wound toward complete healing and reduced the pain level from the wound, suggested to have an anti-inflammatory effect, which contributes to the reduction of pain levels and initiating the natural wound healing process. Conclusion: ActiGraft was found to have a significant effect in reducing wound pain levels, having an impact on the patient’s quality of life, and also progressing hard-to-heal wounds toward complete healing. This synergetic effect establishes ActiGraft as an effective wound healing product in patients with multiple comorbidities, who are suffering from severe background pain related to their wound. Keywords: VLU; autologous blood clot; pain.

Formulation and Evaluation of Fish Collagen Extract into Thin Films

Collagen is a macromolecule of connective tissues in animals and it is cosmopolitan in skin, bones, teeth, tendons, ligament, cartilage, eyes, blood vessels, gut and inter-vertebral discs. Collagen is attracting attention as a biomaterial with several properties such as inducing natural process of blood platelets, cell differentiation, and wound healing, through physical and chemical modifications. The present study was aimed to extract collagen from fish skin and formulate into collagen thin films. Fish collagen thin film was prepared using solvent casting method by using gelatin, sodium alginate, CMC, PEG and ferric oxide, and the formulations were named as F1 to F5. The prepared thin films were cut into strips of area 2X2 cm2 and evaluated for organoleptic evaluations, film weight, thickness, folding endurance, drug content of films, surface pH, disintegration time, in-vitro dissolution studies, moisture loss and uptake and stability studies. The results of the analysis parameters such as weight, thickness, percentage transparency, swelling property, surface pH and folding endurance depends on the concentration of sodium alginate and PEG used. Accelerated stability studies have not shown much remarkable changes in the reading of weight, disintegration time and surface pH, thus it indicates that temperature would not alter the properties of the thin film. From the results of percentage drug release collagen is released fast from F3 (60% in 10 min), and the total drug release was obtained in a span of 40 min, this formulation can be used for the preparation of thin films and F3 total drug release was obtained in 60 min

Tissue Engineering-Based Strategies for Diabetic Foot Ulcer Management.

Significance: Diabetic foot ulcers (DFU) are a mounting problem with the increasingly frail population. Injuries that would otherwise heal are kept open by risk factors such as diabetes, obesity, and age-related conditions, which interferes with the natural wound healing processes. Recent Advances: This review summarizes recent advancements in the field of tissue engineering for the treatment of DFUs. FDA-approved approaches, including signaling-based therapies, stem cell therapies, and skin substitutes are summarized and cutting-edge experimental technologies that have the potential to manage chronic wounds, such as skin printing, skin organogenesis, skin self-assembly, and prevascularization, are discussed. Critical Issues: The standard of care for chronic wounds involves wound debridement, wound dressings, and resolving the underlying cause such as lowering the glycemic index and reducing wound pressure. Current DFU treatments are limited by low wound closure rates and poor regrown skin quality. New adjuvant therapies that facilitate wound closure in place of or in conjunction with standard care are critically needed. Future Directions: Tissue engineering strategies are limited by the plasticity of adult human cells. In addition to traditional techniques, genetic modification, although currently an emerging technology, has the potential to unlock human regeneration and can be incorporated in future therapeutics.

The Regenerative Potential of bFGF in Dental Pulp Repair and Regeneration.

Regenerative endodontic therapy intends to induce the host’s natural wound-healing process, which can restore the vitality, immunity, and sensitivity of the inflammatory or necrotic pulp tissue destroyed by infection or trauma. Myriads of growth factors are critical in the processes of pulp repair and regeneration. Among the key regulatory factors are the fibroblast growth factors, which have turned out to be the master regulators of both organogenesis and tissue homeostasis. Fibroblast growth factors, a family composed of 22 polypeptides, have been used in tissue repair and regeneration settings, in conditions as diverse as burns, ulcers, bone-related diseases, and spinal cord injuries. Meanwhile, in dentistry, the basic fibroblast growth factor is the most frequently investigated. Thereby, the aim of this review is 2-fold: 1) foremost, to explore the underlying mechanisms of the bFGF in dental pulp repair and regeneration and 2) in addition, to shed light on the potential therapeutic strategies of the bFGF in dental pulp–related clinical applications.

In silico investigations on curcuminoids from Curcuma longa as positive regulators of the Wnt/\u03b2-catenin signaling pathway in wound healing

BackgroundCurcuma longa (Turmeric) is a traditionally used herb in wound healing. The efficacy of fresh turmeric paste to heal wounds has already been investigated in multiple ethnobotanical studies. Wnt/β-catenin signaling pathway plays a significant role in wound healing and injury repair processes which has been evident in different in vitro studies. This study aims to analyze the potentiality of curcuminoids (curcumin I, curcumin II and curcumin III) from Curcuma longa to bind and enhance the activity of two intracellular signaling proteins- casein kinase-1 (CK1) and glycogen synthase kinase-3β (GSK3B) involved in Wnt/β-catenin signaling pathway. This study is largely based on a computer-based molecular docking program which mimics the in vivo condition and works on a specific algorithm to interpret the binding affinity and poses of a ligand molecule to a receptor. Subsequently, drug likeness property, ADME/Toxicity profile, pharmacological activity, and site of metabolism of the curcuminoids were also analyzed.ResultsCurcumin I showed better affinity of binding with CK1 (− 10.31 Kcal/mol binding energy) and curcumin II showed better binding affinity (− 7.55 Kcal/mol binding energy) for GSK3B. All of the ligand molecules showed quite similar pharmacological properties.ConclusionCurcumin has anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant, and anti-infective properties. Curcumin has also anti-inflammatory and wound healing properties. It hastens wound healing by acting on different stages of the natural wound healing process. In this study, three curcumins from Curcuma longa were utilized in this experiment in a search for a drug to be used in wound healing and injury repair processes. Hopefully, this study will raise research interest among researchers.

Coupling between macrophage phenotype, angiogenesis and bone formation by calcium phosphates

The ability of calcium phosphate (CaP) materials to induce bone formation varies with their physicochemical properties, with surface topography as one of the most crucial triggers. In view of the natural wound healing processes (e.g., inflammation, angiogenesis, tissue formation and remodeling) initiated after surgical implantation, we here comparatively investigated the biological cascades occurring upon ectopic implantation of a tricalcium phosphate with submicron surface topography (TCP-S, osteoinductive) and a tricalcium phosphate with micron-scale topography (TCP-B, non-osteoinductive). In vitro, TCP-S facilitated M2 polarization of macrophages derived from a human leukemic cell line (THP-1) as shown by the enhanced secretion of TGF-β and CCL18. Interestingly, the conditioned media of polarized M2 macrophages on TCP-S enhanced tube formation by human umbilical vein endothelial cells (HUVECs), while had no influence on the osteogenic differentiation of human bone marrow stromal cells (HBMSCs). Following an intramuscular implantation in canines, TCP-S locally increased typical M2 macrophage markers (e.g., IL-10) at week 1 to 3 and enhanced blood vessel formation after week 3 as compared to TCP-B. Bone formation was observed histologically in TCP-S 6 weeks after implantation, and bone formation was inhibited when an angiogenesis inhibitor (KRN633) was loaded onto TCP-S. No bone formation was observed for TCP-B. The data presented herein suggest strong links between macrophage polarization, angiogenesis and CaP-induced bone formation. Statement of significanceThe ability of calcium phosphate (CaP) materials to induce bone formation varies with their physicochemical properties, and the key physicochemical properties relevant to CaP-induced bone formation have been outlined in the last two decades. However, the biological mechanism underlying this material-driven osteoinduction remains largely unknown. This manuscript presented demonstrates strong links between surface topography, macrophage polarization, angiogenesis and bone formation in CaP materials implanted in non-osseous sites. The finding may provide new clues for further exploring the possible mechanism underlying osteoinduction by CaP materials.