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Potential role of bromelain in clinical and therapeutic applications

Rathnavelu V, Alitheen NB, Sohila S, Kanagesan S, Ramesh R

Biomed Rep, 2016 Sep;5(3):283-288.
PMID: 27602208

Pineapple has been used as part of traditional folk medicine since ancient times and it continues to be present in various herbal preparations. Bromelain is a complex mixture of protease extracted from the fruit or stem of the pineapple plant. Although the complete molecular mechanism of action of bromelain has not been completely identified, bromelain gained universal acceptability as a phytotherapeutic agent due to its history of safe use and lack of side effects. Bromelain is widely administered for its well-recognized properties, such as its anti-inflammatory, antithrombotic and fibrinolytic affects, anticancer activity and immunomodulatory effects, in addition to being a wound healing and circulatory improvement agent. The current review describes the promising clinical applications and therapeutic properties of bromelain.

Matched MeSH terms: Wound Healing
Fulltext Signaling pathways promoting epithelial mesenchymal transition in oral submucous fibrosis and oral squamous cell carcinoma

Shetty SS, Sharma M, Fonseca FP, Jayaram P, Tanwar AS, Kabekkodu SP, et al.

Jpn Dent Sci Rev, 2020 Nov;56(1):97-108.
PMID: 32874377 DOI: 10.1016/j.jdsr.2020.07.002

Epithelial-mesenchymal transition (EMT) is a critical process that occurs during the embryonic development, wound healing, organ fibrosis and the onset of malignancy. Emerging evidence suggests that the EMT is involved in the invasion and metastasis of cancers. The inflammatory reaction antecedent to fibrosis in the onset of oral submucous fibrosis (OSF) and the role of EMT in its malignant transformation indicates a hitherto unexplored involvement of EMT. This review focuses on the role of EMT markers which are regulators of the EMT mediated complex network of molecular mechanisms involved in the pathogenesis of OSF and OSCC. Further the gene enrichment analysis and pathway analysis supports the association of the upregulated and downregulated genes in various EMT regulating pathways.

Matched MeSH terms: Wound Healing
Fulltext Comprehensive Review of Hybrid Collagen and Silk Fibroin for Cutaneous Wound Healing

Naomi R, Ratanavaraporn J, Fauzi MB

Materials (Basel), 2020 Jul 10;13(14).
PMID: 32664418 DOI: 10.3390/ma13143097

The use of hybridisation strategy in biomaterials technology provides a powerful synergistic effect as a functional matrix. Silk fibroin (SF) has been widely used for drug delivery, and collagen (Col) resembles the extracellular matrix (ECM). This systematic review was performed to scrutinise the outcome of hybrid Col and SF for cutaneous wound healing. This paper reviewed the progress of related research based on in vitro and in vivo studies and the influence of the physicochemical properties of the hybrid in wound healing. The results indicated the positive outcome of hybridising Col and SF for cutaneous wound healing. The hybridisation of these biomaterials exhibits an excellent moisturising property, perfectly interconnected structure, excellent water absorption and retention capacity, an acceptable range of biodegradability, and synergistic effects in cell viability. The in vitro and in vivo studies clearly showed a promising outcome in the acceleration of cutaneous wound healing using an SF and Col hybrid scaffold. The review of this study can be used to design an appropriate hybrid scaffold for cutaneous wound healing. Therefore, this systematic review recapitulated that the hybridisation of Col and SF promoted rapid cutaneous healing through immediate wound closure and reepithelisation, with no sign of adverse events. This paper concludes on the need for further investigations of the hybrid SF and Col in the future to ensure that the hybrid biomaterials are well-suited for human skin.

Matched MeSH terms: Wound Healing
Management of dry socket with low-level laser therapy

Kamal A, Salman B, Ar NH, Samsudin AR

Clin Oral Investig, 2021 Mar;25(3):1029-1033.
PMID: 32562076 DOI: 10.1007/s00784-020-03393-3

OBJECTIVE: The aim of this study is to investigate the efficacy of delivering low-level laser therapy (LLLT) in the management of dry socket at University Dental Hospital Sharjah.
MATERIALS AND METHOD: Forty-five patients with dry socket were divided into two treatment groups. Group I dry socket patients (n = 30) received conventional treatment while group II patients (n = 15) were irradiated with LLLT at a setting of 200-mW, 6-J, continuous-wave mode using an R02 tipless handpiece (Fotona Er:YAG, Europe), on the buccal, lingual, and middle surfaces of the socket for 30 s from a delivery distance of 1 cm. Pain score and quantification of granulation tissue in the socket were recorded at 0, 4, and 7 days post-dry socket treatment.
RESULTS: Results showed that the LLLT-irradiated group II sockets showed a much lower VAS pain score of 1-2 as early as day 4, and a richer amount of granulation tissue compared to the conventional treated group I socket. The amount and rate of granulation tissue formation in the dry socket are inversely proportional to the pain score showing significant clinical effectiveness of LLLT on promoting the healing of the dry socket, with improvement in symptoms (P = .001). Conventionally treated dry sockets take at least 7 days to match the effective healing of an LLLT-irradiated dry socket.
CONCLUSION: LLLT irradiation influences biomodulation of dry socket healing by dampening inflammation, promoting vascularization, stimulating granulation, and controlling pain symptoms.
CLINICAL RELEVANCE: LLLT may be an additional effective tool for managing dry sockets in general dental practice.

Matched MeSH terms: Wound Healing
In vitro evaluation of antioxidant and antibacterial activities of Eucheuma cottonii extract and its in vivo evaluation of the wound-healing activity in mice

Teo BSX, Gan RY, Abdul Aziz S, Sirirak T, Mohd Asmani MF, Yusuf E

J Cosmet Dermatol, 2021 Mar;20(3):993-1001.
PMID: 32659861 DOI: 10.1111/jocd.13624

BACKGROUND: Eucheuma Cottonii is a type of red algae obtained from Sabah with main active component, sulfated polysaccharide or k-carrageenan.
AIMS: The objective of this research was to evaluate the antioxidant, antibacterial and potential wound-healing properties in aqueous extraction of E cottonii in order to meet the increasing demand for halal and natural cosmeceutical products.
METHODS AND RESULTS: Aqueous extract of E cottonii was investigated for active compounds by phytochemical screening and IR spectroscopy. Antioxidant activity was carried out using DPPH method, and the IC50 value was 1.99 mg/mL. Antibacterial activity was examined against Staphylococcus Aureus using Kirby-Bauer disk diffusion method and showed 10.03 ± 0.06 mm zone of inhibition, achieved by 200 mg/mL of extracts. A wound was made by skin excision of area around 100 mm2 on each mouse. Test group was treated with aqueous extract gel (10% w/w); meanwhile, the mice that were treated with honey acted as the positive control group and the untreated mice as negative control group. Results showed that the wound contraction rate inclined to aqueous extracts as compared to untreated group (P wound healing for aqueous extracts and untreated group were 87.7% ± 2.0% and 57.6% ± 5.3%, respectively.
CONCLUSION: Aqueous extract was found to be comparable to the honey in wound healing.

Matched MeSH terms: Wound Healing
Fulltext Profiles and biological values of sea cucumbers: a mini review

Siti Fathiah Masre

Life Sciences, Medicine and Biomedicine, 2018;2(4):7-11.
MyJurnal

Sea cucumbers, blind cylindrical marine invertebrates that live in the ocean intertidal beds have more than thousand species available of varying morphology and colours throughout the world. Sea cucumbers have long been exploited in traditional treatment as a source of natural medicinal compounds. Various nutritional and therapeutic values have been linked to this invertebrate. These creatures have been eaten since ancient times and purported as the most commonly consumed echinoderms. Some important biological activities of sea cucumbers including anti-hypertension, anti-inflammatory, anti-cancer, anti-asthmatic, anti-bacterial and wound healing. Thus, this short review comes with the principal aim to cover the profile, taxonomy, together with nutritional and medicinal properties of sea cucumbers.

Matched MeSH terms: Wound Healing
Fulltext Acceleration of wound healing by orthosiphon stamineus leaf extract in rats

Mahmood, A.A., Hapipah, M.A., Noor, S.M., Kuppusamy, U.R., Salmah, I., Salmah, I., et al.

ASM Science Journal, 2009;3(1):51-57.
MyJurnal

The effects of topical application of Orthosiphon stamineus leaf extract on the rate of wound healing and histology of the healed wound were assessed. Four groups of adult male Sprague Dawley rats were experimentally wounded in the posterior neck area. A thin layer of blank placebo was applied topically to wounds of Group 1 rats. Wounds of experimental animals (Group 2 and 3) were dressed with placebo containing 5% and 10% O. stamineus extract, respectively. A thin layer of Intrasite gel® was applied topically to wounds of Group 4 animals as reference. Macroscopically, wounds dressed with placebo containing 5% (healed on day 14.50 ± 0.43) and 10% (healed on day 13.83 ± 0.21) O. stamineus extract each or Intrasite gel® (healed on day 13.13 ± 0.42) significantly accelerated the rate of wound healing compared to wounds dressed with blank placebo. Histological analysis of healed wounds confirmed the results. Wounds dressed with placebo containing 5%, 10% O.stamineus or Intrasite gel® showed markedly less scar width at wound enclosure and granulating tissue contained markedly more collagen, proliferating fibroblast with angiogenesis, and no inflammatory cells compared to wounds dressed with blank placebo. In conclusion, placebo containing 5% or 10% O. stamineus on extract-dressed wounds significantly accelerated the rate of wound healing in rats.

Matched MeSH terms: Wound Healing
Fulltext Determining the effectiveness of the different preparation protocols for platelet-rich plasma (PRP) in yielding higher concentrations of platelets

Kavitha, G., Sangeetha, V.N., Shani, S., Murali, M.R., Raja, E.A., Rukmanikanthan, S., et al.

JUMMEC, 2011;14(2):1-6.
MyJurnal

INTRODUCTION: Despite the various methods described in producing platelet-rich plasma (PRP), it is well established that this biological product in its many preparations have been proven to enhance wound healing. However, very little have been known about the efficacy of these methods hence there is a lack of evidence in the superiority of one method over another. Thus, a study was conducted to compare these different protocols to determine which produces the highest concentration of platelets.
METHODS: Peripheral blood was obtained from 24 healthy volunteers. Four different protocols using similar 2 step centrifugation methods of preparing PRP were applied to an equal number of samples in this study. Platelet counts were performed on whole blood (without processing), PRP preparations and platelet-poor plasma (PPP).
RESULTS: All protocols produced higher amounts of platelet concentrates in PRP preparations than plasma. However, centrifugation at 150g for 10 minutes followed by another at 450g at 10 minutes produces significantly higher amount of platelets concentration (p<0.05)
CONCLUSION: Optimizing the protocols to produce PRP appears to be important in obtaining a maximal yield of platelet concentrate. Here the protocol described has shown to provide significant concentration yield over all others.
Keywords: platelet-rich-plasma, growth factors, centrifugal forces

Matched MeSH terms: Wound Healing
Low-factor consumption for major surgery in haemophilia B with long-acting recombinant glycoPEGylated factor IX

Escobar MA, Tehranchi R, Karim FA, Caliskan U, Chowdary P, Colberg T, et al.

Haemophilia, 2017 Jan;23(1):67-76.
PMID: 27480487 DOI: 10.1111/hae.13041

INTRODUCTION: Surgery in patients with haemophilia B carries a high risk of excessive bleeding and requires adequate haemostatic control until wound healing. Nonacog beta pegol, a long-acting recombinant glycoPEGylated factor IX (FIX), was used in the perioperative management of patients undergoing major surgery.
AIM: To evaluate the efficacy and safety of nonacog beta pegol in patients with haemophilia B who undergo major surgery.
METHODS: This was an open-label, multicentre, non-controlled surgery trial aimed at assessing peri- and postoperative efficacy and safety of nonacog beta pegol in 13 previously treated patients with haemophilia B. All patients received a preoperative nonacog beta pegol bolus injection of 80 IU kg-1 . Postoperatively, the patients received fixed nonacog beta pegol doses of 40 IU kg-1 , repeated at the investigator's discretion. Safety assessments included monitoring of immunogenicity and adverse events.
RESULTS: Intraoperative haemostatic effect was rated 'excellent' or 'good' in all 13 cases. Apart from the preoperative injection, none of the patients needed additional doses of nonacog beta pegol on the day of surgery. The median number of postoperative doses of nonacog beta pegol was 2.0 from days 1 to 6 and 1.5 from days 7 to 13. No unexpected intra- or postoperative complications were observed including deaths or thromboembolic events. No patients developed inhibitors.
CONCLUSIONS: These results indicated that nonacog beta pegol was safe and effective in the perioperative setting, allowing major surgical interventions in patients with haemophilia B with minimal peri- and postoperative concentrate consumption and infrequent injections as reported with standard FIX products.
KEYWORDS: Phase III; factor IX; haemophilia B; long-acting recombinant factor IX; nonacog beta pegol; surgery

Matched MeSH terms: Wound Healing
Fulltext The Effects Of CO2 Laser On Oral Lichen Planus And Lichenoid Lesions

Kok, T.C., Ong, S.T.

Ann Dent, 2001;8(1):-.
MyJurnal

The purpose of this study is to assess the effectiveness of C02 laser in relieving symptoms associated with Oral lichen planus (aLP) and lichenoid lesions (aLL) and the event of healing. Six patients were selected for this study with 13 sites treated. Each lesion was ablated with C02 laser and the wound allowed to heal undisturbed. Prior to treatment, 4 patients had both unprovoked and provoked pain and 2 patients rated for provoked pain only. After laser ablation, five out of six patients treated recorded no pain / 0 pain score. One month post-laser, the treated area was almost the same colour as the surrounding normal mucosa and soft in texture in all but one patient in which there was some fibrosis and residual plaque-like patch. Weconclude that the use of C02 laser in the treatment of aLP and aLL shows positive results in relieving symptoms associated with these lesions.

Matched MeSH terms: Wound Healing
Fulltext A review on hydroxyapatite-based scaffolds as a potential bone graft substitute for bone tissue engineering applications

Krishnamurithy, G.

JUMMEC, 2013;16(2):1-6.
MyJurnal

The biocompatibility and similarity of hydroxyapatite (HA) to the mineral composition of the bone has made HA a potential candidate in bone tissue engineering (BTE). Over the past few decades, its application as bone graft in combination with stem cells has gained much importance. The use of bone marrow-derived mesenchymal stromal cells (MSCs) will enhance the rate and quality of defect repair. However, application of hydroxyapatite as a material to develop a 3-dimension scaffold or carrier to support MSCs in vitro is still in its infant stage. This review will discuss the source, manufacturing methods and advantages of using HA scaffolds in bone tissue engineering applications.

Matched MeSH terms: Wound Healing
Fulltext Patching up the bone – a case report of autologous fibrin matrix in combination with autogenous bone graft for bone and soft tissue regeneration

Mohd Kherman Suparman, Hazmyr Abdul Wahab, Nazer Berahim, Tengku Intan Baizura Tengku Jamaluddin

Malaysian Dental Journal, 2017;2017(1):1-12.
MyJurnal

Platelet Rich Fibrin (PRF) is a natural autologous fibrin matrix and is an effective biomaterial product. The application of PRF in oral surgery is not limited to tissue regeneration, but it has been utilized in several minor and major oral surgical procedures. Numerous studies have proven that either alone or in combination with bone graft, PRF acts as bone and soft tissue regeneration and it is able to stimulate physiological wound healing. This case report will introduce the utilization of PRF combined with autogenous bone graft in restoring four walls dental socket defect due to post-surgical extraction complication and plan for implant placement in the future. It acts in the form of a resorbable membrane and stem cell connector to the bone. After 3 months post-surgery review, there was no signs of infection or tissue rejection and the harvested bone was still viable. The PRF is comparable to commercially available membrane in the market, where clinical results can be predicted and possibility of reduction in post-surgical complications is achieved. This is due to 1) its compatibility with bone graft materials notably autogenous type, 2) induced neovascularisation and 3) reduction in inflammatory reaction. Our team is confident that the result of PRF at the edentulous region for rehabilitation purposes is beneficial and cost-effective to our patients.

Matched MeSH terms: Wound Healing
Fulltext Combination effect of argan oil and low frequency electromagnetic field on open wound in mice

Siti F. Masre, Muzamir, M.K, Sabarina, I., Jehan, N., Yanti Rosli

Jurnal Sains Kesihatan Malaysia, 2018;16(101):41-45.
MyJurnal

This study was conducted to evaluate the effect of argan oil with the exposure of low frequency electromagnetic field (EMF) on open wound healing in mice. Eighteen male mice (20-40 g) were divided into three groups: phosphate buffer saline (PBS) as negative control, solcoseryl gel as positive control, and argan oil with the exposure of low frequency EMF, 1.2 mT (treatment group). Full thickness wounds (4 mm diameter) were induced on the shaved dorsal of the mouse. All mice were sacrificed on day 12 after the final treatment. Macroscopic observation, wound contraction rate, histopathology analysis and total protein content were examined in this study. Results showed that wounds treated with argan oil and exposed to low frequency EMF has a significant increase in wound contraction rate (p < 0.05) and total protein content (p < 0.05). Moreover, histopathological analysis on the wound tissues displayed complete re-epithelization with thick and dense collagen fibers in the argan oil with low frequency EMF exposure treated group. In conclusion, topical treatment of argan oil with low frequency EMF exposure yield a better healing progress and showed the ability to accelerate wound healing

Matched MeSH terms: Wound Healing
Fulltext The guru-UKM method: synergistic effect of hydrogel, hydrofibre and dermal conservation in burn wound management

Farrah-Hani Imran, Ian, Chik, Kelly, Enda Gerard, Razman Jarmin

International Medical Journal Malaysia, 2018;17(3):89-94.
MyJurnal

Initial wound care idioms were designed around a moist dressing in presumed better wound healing. As wound care advances, innovations of dressings were formed. In the Guru-UKM Method (GUM), we combined two well-established dressings producing a synergistic effect in burn wound management. Patients with deep partial thickness burns were selected for the GUM. From the time of admission, they receive 2 cycles of paraffin tulle dressings once every two days to allow demarcation, then are reassessed for suitability of the GUM technique. We discuss 7 different burn cases that presented to our Burn Unit from January 2014 – June 2015.All dressings should create a suitable moist environment for healing, yet should be a painless dressing to help the patient return to normal function as soon as possible. In burn wounds, a suitable dressing ideally also biochemically debrides fibrin and softens hardened eschar and slough, without necessitating the patient to undergo general anaesthesia and surgical debridement. The Guru-UKM Method is a combination dressing technique that facilitates optimal burn wound management.

Matched MeSH terms: Wound Healing
The treatment of wounds

Cameron JAP

Journal of the Malaya Branch of the British Medical Association, 1939;3:297-304.

Matched MeSH terms: Wound Healing
Fulltext Physical, mechanical, chemical and biological properties data of gellan gum incorporating titanium dioxide nanoparticles biofilm

Razali MH, Ismail NA, Amin KAM

Data Brief, 2020 Jun;30:105478.
PMID: 32346560 DOI: 10.1016/j.dib.2020.105478

Gellan gum incorporating titanium dioxide nanoparticles biofilm was synthesized and characterized using UV, FTIR and XRD to study their physical and chemical properties. The mechanical properties were measured using universal mechanical testing. Meanwhile, the biological properties were investigated towards for antibacterial and cell proliferation. This comprehensive data are relevant with the research article entitled "Gellan gum incorporating titanium dioxide nanoparticles biofilm as wound dressing: Physicochemical, mechanical, antibacterial properties and wound healing studies" [1].

Matched MeSH terms: Wound Healing
Maggot debridement therapy to treat hard-to-heal diabetic foot ulcers: a single-centre study

Nair HK, Ahmad NW, Ismail AA, Alabed AAA, Zheming BO, Kaur G, et al.

J Wound Care, 2021 12 01;30(Sup12):S30-S36.
PMID: 34882006 DOI: 10.12968/jowc.2021.30.Sup12.S30

OBJECTIVE: Maggot debridement therapy (MDT) has seen a resurgence in recent years in the treatment of hard-to-heal wounds, as a result of rising antibiotic resistance. The sterilised larvae of Lucilia cuprina have been used in MDT in Malaysia since 2003, with encouraging results for the treatment of hard-to-heal diabetic wounds. We report a case series of 30 patients selected from our clinic by convenient sampling with diabetic lower limb ulcers treated with MDT. The average age of patients receiving MDT was >50 years. Of the 30 patients in the study, nine were female and 21 were male. All patients had underlying diabetes, two patients had leg ulcers and 28 patients had diabetic foot ulcers. Sterilised Lucilia cuprina larvae were applied via a standard method of 10 maggots per square centimetre and dressed with sterile gauze. The study endpoint was defined as ≤5% coverage with slough or necrotic tissue following three successive applications of MDT. In this study, maximum debridement of wounds was achieved in 96.6% (29 patients) of our patients, with ≤5% coverage with slough or necrotic tissue, in addition to a reduction in wound-related pain, as assessed by a visual analogue scale. No adverse events were reported. The findings of this study support the use of MDT as a safe, efficacious, and cost-effective method of managing diabetic wounds.

Matched MeSH terms: Wound Healing
Third-degree burn mouse treatment using recombinant human fibroblast growth factor 2

Tran-Nguyen TM, Le KT, Nguyen LT, Tran TT, Hoang-Thai PC, Tran TL, et al.

Growth Factors, 2020 12;38(5-6):282-290.
PMID: 34415815 DOI: 10.1080/08977194.2021.1967342

Fibroblast growth factor 2 (FGF-2) is a multifunctional protein that has major roles in wound healing, tissue repair, and regeneration. This therapeutic protein is widely used for burn treatment because it can stimulate cell proliferation and differentiation, angiogenesis, and extracellular matrix remodeling. In this study, we developed a simple method using a controlled heated brass rod to create a homogenous third-degree burn murine model and evaluated the treatment using recombinant human FGF-2 (rhFGF-2). The results indicated that the wound area was 0.83 ± 0.05 cm2 and wound depth was 573.42 ± 147.82 μm. Mice treated with rhFGF-2 showed higher rates of wound closure, granulation tissue formation, angiogenesis, and re-epithelialization than that of phosphate-buffered saline (PBS)-treated group. In conclusion, our lab-made rhFGF-2 could be a potentially therapeutic protein for burn treatment as well as a bioequivalent drug for other commercial applications using FGF-2.

Matched MeSH terms: Wound Healing
Fulltext Role of MicroRNA in Proliferation Phase of Wound Healing

Soliman AM, Das S, Abd Ghafar N, Teoh SL

Front Genet, 2018;9:38.
PMID: 29491883 DOI: 10.3389/fgene.2018.00038

Wound healing is a complex biological process that is generally composed of four phases: hemostasis, inflammation, proliferation, and remodeling. The proliferation phase is crucial for effective healing compared to other phases. Many critical events occur during this phase, i.e., migration of fibroblasts, re-epithelialization, angiogenesis and wound contraction. Chronic wounds are common and are considered a major public health problem. Therefore, there is the increasing need to discover new therapeutic strategies. MicroRNA (miRNA) research in the field of wound healing is in its early phase, but the knowledge of the recent discoveries is essential for developing effective therapies for the treatment of chronic wounds. In this review, we focused on recently discovered miRNAs which are involved in the proliferation phase of wound healing in the past few years and their role in wound healing.

Matched MeSH terms: Wound Healing
Fulltext Evaluation of in vitro wound healing efficacy of breadfruit derived starch hydrolysate

Amin, Z.M., Koh, S.P., Tan, C.P., Yeap, S.K., Hamid, N.S.A., Long, K.

International Food Research Journal, 2017;24(4):1771-1781.
MyJurnal

To study the wound healing efficacy of breadfruit starch hydrolysate, an in vitro wound scratch assay was conducted, in which the migration rate of wounded NIH 3T3 fibroblasts was determined. Wounds treated with lower dextrose equivalent (DE), (DE 10-14) starch hydrolysate were found capable to improve the wound healing of NIH 3T3 fibroblast cell with the percentage of wound closure improvement of 77%, respectively when compared with higher DE range (DE 15-19 and DE 20-24). The findings obtained in the BrdU uptake and MTT viability assays confirmed the wound healing properties of breadfruit starch hydrolysate as the starch hydrolysate-treated wounded NIH 3T3 fibroblasts were able to proliferate well and no cytotoxicity was observed. Together, these findings indicated that the newly developed breadfruit starch hydrolysate performed better than commercial (COM) starch hydrolysate of the same DE ranges. In conclusion, breadfruit starch hydrolysate had better functional properties than did starch hydrolysates derived from other sources and that they could play a beneficial role in wound healing applications.

Matched MeSH terms: Wound Healing

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