Abstract
Abstract
Wound healing is a biological complex process that involves several cell types under the control and regulation of several growth factors and cytokines. There have been efforts to study the therapeutic effects of granulocyte-macrophage colony-stimulating factor, platelet-derived growth factor, transforming growth factor-β, vascular endothelial growth factor and basic fibroblast growth factor on chronic wounds. In addition, the effects of biomaterials such as nano-fibrous chitin and chitosan have been proven to be effective on wound healing. Furthermore, stem cell therapy using adipose-derived stem cells (ASCs) has been developed as a new therapeutic method for wound repair and healing. In this review, we will summarize the role of stem cells; growth factors and biomaterials in wound healing and repair.
Introduction
Wound healing is a normal biological process following a soft tissue injury and it’s a highly organized cascade of events that includes phases such as haemostasis, inflammation, proliferation and remodelling [1]. Therefore, interference with any of the four stages during the wound healing can result into an impaired healing process [2]. During chronic wounds, regeneration of tissue is arrested in the inflammatory stage that can result to pathologic inflammation and failure of initiation of advanced stages of wound healing [3]. Mulder et al. stated that there is an abnormal production of inflammatory cytokines when there is a prolonged inflammatory phase [4]. Hence, the increased presence of neutrophils cells can act as a marker for chronic wounds [5,6]. According to Guo et al. the extracellular matrix (ECM) has been degraded as a result of an increase in inflammatory cells and which ultimately leads to increase in secretion of matrix metalloproteinases (MMPs) and loss of vital growth factors necessary for proper wound healing [7,8]. Table 1 shows the important factors involved in chronic wounds.
Table 1. Factors affecting chronic wounds.
Stem cells application in wound healing
Stem cells are cells that can retain prolonged self-renewal ability and can differentiate into numerous tissue types [9]. There are different sources of stem cells such as embryonic stem cells, induced pluripotent stem cells, bone marrow stem cells (BMSCs) and adipose-derived stem cells (ASCs) [10]. Various researchers have reported the use of stem cells as a potential wound healing agent in both preclinical and clinical cases, mainly in critical limb ischemia and diabetic wounds [11–13]. Aranguren et al. reported the administration of BMSCs and peripheral-derived mononuclear cells to patients with chronic wounds [13]. Topical delivery of bone marrow-derived mesenchymal stem cells (MSCs) on a collagen sponge scaffold has been reported by Yoshikawa et al. to show positive significant improvement in wound healing [14] in 18 of 20 patients. In other similar and separate clinical studies, autologous biograft and MSCs was demonstrated to improve a diabetic wound healing [15].
Adipose-derived stem cells role in wound healing
Park et al. [16] reported the examination of the secretion profile of ASCs in their study. They found out that the cells secreted by ASCs were transforming growth factor (TGF-β), vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), fibroblast growth factor 2 (FGF2) [17], fibronectin and collagen I [18], and these factors have been said to speed up the process of wound healing in normal and chronic wounds [19]. In another preclinical study of chronic wound, a mouse model is used to evaluate the efficiency of ASCs [20] full-thickness skin wound. Histological examination was done and it showed a prolonged healing time, increased epithelialization rate, increased rate of granulation tissue formulation and higher capillary formation rate when compared with control groups [21]. Altman et al. [22] reported that seeded ASCs on silk suture could be efficient in closing full-thickness skin wounds in mice (Table 2). ASCs can enhance tissue regeneration by either differentiating into skin type cells or by secreting paracrine factors, which results into initiation of healing process or inhibiting inflammatory response (Figure 1).
Published online:
15 February 2018Figure 1. Showing potential mechanism of skin repair by ASCs. This figure was adapted from [46] with copyright permission.
![]({"type":"image","src":"/na101/home/literatum/publisher/tandf/journals/content/ianb20/2018/ianb20.v046.sup01/21691401.2018.1439836/20220203/images/medium/ianb_a_1439836_f0001_c.jpg"})
Figure 1. Showing potential mechanism of skin repair by ASCs. This figure was adapted from [46] with copyright permission.
Table 2. Showing applications of ASCs in wound healing.
Adipose-derived stem cells and growth factors
ASCs have been reported to secrete several growth factors such as insulin-like growth factor (IGF), hepatocyte growth factor (HGF), transforming growth factor-beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF) [23]. ASCs also secrete factors in vitro that can stimulate proliferation of fibroblasts and keratinocytes. Wu et al. [24] demonstrated that injection of BMSCs markedly improved the closure of wound and strength in diabetic mouse model for wound healing. In another similar study, conditioned medium (CM) derived from BMSCs have been reported to enhance wound-healing response by Kim et al. They concluded in their study that CM derived from BMSCs increased collagen synthesis thereby leading to enhanced wound healing [18]. Galiano et al. [25] also in their study demonstrated that VEGF can possibly enhance wound healing in a genetically diabetic mice model. The healing process was confirmed by the angiogenesis in the wound bed and recruitment of BMSCs [26].
Clinical application of adipose-derived stem cells
Clinical application of ASCs as a therapeutic alternative is widely adopted because it’s easy to harvest fat tissue, abundant and ethical concerns does not in fact exist [27]. Recently, ASCs have been reported to be efficient in preclinical studies of chronic wounds and as such ASCs studies have progressed from translational phase into clinical trials [28]. Table 3 shows the use of ASCs in various available clinical trials [29]. Lendeckel et al. [30] were among the first researchers to report the clinical use of ASCs using stromal vascular fraction (SVF) in a case report to treat calvaria defect after head injury. In their report, they used fibrin glue combined with SVF [31]. They concluded that there was newly formed cranial bone after three months post-surgical treatment and there were also clear evidences of near total healing of calvaria defect. Mesimäki et al. in their study, reported that ASCs combined with bone morphogenic protein (BMP-2) and tricalcium phosphate scaffold resulted in effective healing of osteogenic defect [32]. The management and treatment of Crohn’s disease has been reported to be achieved via the administration of ASCs [33].
Table 3. Showing clinical trials, involving the use of ADSCs.
Growth factors and the process of wound healing
Platelet-derived growth factor (PDGF)
PDGF plays a vital role in each phase of wound healing process. As reported by Trengove et al., PDGF is released from de-granulating platelets following an injury into the wound fluid [34]. PDGF initiates inflammatory response by stimulating mitogenicity and chemotaxis abilities of cells such as neutrophils, macrophages, fibroblasts and smooth muscle cells to the site of the wound [35]. The role of PDGF has been identified during the epithelialization stage of wound healing to up-regulate the production of growth factors such as insulin growth factor (IGF)-1 and thrombospondin-1 and inturn IGF-1 increases the motility of keratinocyte cells and thrombospondin-1 inhibits proteolytic and enzymatic degradation of PDGF [36]. Becaplermin is an FDA rh-PDGF approved drug for the treatment of DFUs and has shown to fast-track the process of wound closure in DFUs in randomized clinical trials (Table 3).
Fibroblast growth factor (FGF)
Several members of the fibroblast growth factor family (FGF) have been reported to play important roles in the process of wound healing [37]. The sources of FGFs are keratinocytes, fibroblasts, endothelial cells, smooth muscle cells, chondrocytes and mast cells [38]. Di Vita et al. stated that during acute wound, there is a rise in the production of FGF-2 and are said to be responsible in granulation tissue formation, re-epithelialization and tissue remodelling [39]. Furthermore, synthesis and deposition of several extracellular matrix constituents and increased keratinocyte motility in vitro studies are regulated by FGF-2 [40]. Table 3 shows the use of FGF in available clinical trials [41].
Vascular endothelial growth factor (VEGF)
VEGF family consist of several members, and one of its member such as VEGF-A initiates the process of wound healing by promoting biological processes and events such as early angiogenesis and especially migration of endothelial cell [42]. Administration of VEGF-A has been reported to restore impaired angiogenesis process in diabetic ischemic limbs in an animal model as well as improving re-epithelialization process of diabetic wounds [43]. Table 4 shows randomized controlled trials using several VEGF-based therapies for wound healing.
Table 4. Showing application of growth factors and cytokines in wounds healing.
Biomaterials and wound healing process
Various reports on the useful effects of biomaterials such as chitin and chitosan for wound healing have surfaced recently [44]. Chitin and chitosan are the most applied biomaterials for wound healing, and recently isolation and production of nanofibrillar chitin and chitosan have been formulated and as such the use of chitin and chitosan has been exhibited in wound healing [45]. Table 5 and 6 represent the summary of the various uses of chitin and chitosan for wound healing, respectively.
Table 5. Showing the application of chitin in wound healing.
Table 6. Selected applications of chitosan as a wound-dressing biomaterial.
Conclusions
Biomaterials such as chitosan and chitin have been established to be an efficient biomaterial to stimulate wound healing. Various studies have reported that these biomaterials are non-toxic, biodegrading slow rate and biocompatible material that make chitin and chitosan important biomaterials for wound healing. The use and administration of growth factors and cytokines have been described to be necessary for the initiation and regulation of the process of wound healing and can also serve as a potential therapeutic alternative for healing wounds. Growth factors such as GM-CSF, PDGF, bFGF and VEGF have been shown to be a potential therapeutic means for wound healing in various randomized controlled trials. However, there is still need for larger randomized controlled trials to be carried out to investigate side-effect profiles and long-term effects. Furthermore, pre-clinical studies have shown that ASCs are effective for wound healing in animal models of chronic wounds. However, ASCs are said to secrete growth factors, cytokines and chemo-attractants that can promote the process of angiogenesis and increase blood supply thus supporting the tumour growth as such; more research work and clinical studies are still needed to extensively investigate this side-effects.
| Specific factors | Physiological factors |
|---|---|
| Exposure of wound to bacteria, viral or parasitic infections | Aging process can lead to development chronic wound |
| Reduced blood and oxygen flow to a wound | Chronic diseases such as cancer and genetic disorder diseases. |
| Presence of cancerous cells | Presence of alcohol and cannabis |
| Exposure of wound to radiation | Taking harmful drugs can lead to chronic wound |
| Trauma | Nutritional deficiencies |
| Secretion of local toxins | Presence of urea in the blood |
| Arterial/venous insufficiency | Impairment in the functions of the peripheral nerve |
Adapted from [46] with copyright permission.
| Reference | Methods |
|---|---|
| [11] | Shows the application of ASCs in the formulation of collagen gel |
| [24] | Demonstrated the use of ASCs in the design of an atelocollagen scaffold |
| [47] | Demonstrated the use of ASCs in the design of a silk fibroin scaffold |
| [25] | Reported the injection of ASCs |
| [18] | Reported the direct injection of ASCs |
| [29] | Reported the injection of ASCs |
| [21] | Reported the application of noncultured ASCs in the formulation of an atelocollagen matrix |
| [30] | Reported the use of ASCs in platelet-rich plasma |
| [32] | Demonstrated the direct injection of ASCs into chronic wounds |
| [33] | Demonstrated the direct injection of ASCs into chronic wounds |
| [34] | Demonstrated the injection of ASCs into flap |
| [38] | Demonstrated the direct injection of ASCs around the wound site |
| [40] | Reported the use of ASCs in the formulation of collagen gels |
| [42] | Showed the application of ASCs on acellular dermal matrix |
| [43] | Formulated a conditioned medium of genetically modified ASCs |
Adapted from [46] with copyright permission.
| Clinical trials | Clinical trial number |
|---|---|
| Allogenic ADSCs in Crohn’s Fistula | NCT01440699 |
| Autologous Cultured ADSCs on Complex and Crohn’s Fistula | NCT01314092 |
| Development of Bone Grafts Using ADSCs and Different Scaffolds | NCT01218945 |
| ADSCs to Treat Complex Perianal Fistulas | NCT01020825 |
| Safety and Effects of Autologous Adipose-Derived Stromal Cells Delivered in Patients with Renal Failure | NCT01453816 |
| Human Adipose-Derived MSCs for Critical Limb Ischemia in Diabetic Patients | NCT01257776 |
| Autologous ADSCs in Patients after Stroke | NCT01453829 |
| Autologous-Cultured Adipocytes in Patient with Depressed Scar | NCT00992147 |
Adapted from https://clinicaltrials.gov.
| Growth factor | Brand name | Administration | Wound type |
|---|---|---|---|
| Recombinant human granulocyte-macrophage colony-stimulating factor | Leukine | Subcutaneous injection | Chronic venous ulcers |
| Recombinant human granulocyte colony-stimulating factor | Leucomax | Second-degree burns | |
| Diabetic foot ulcers | |||
| Recombinant human platelet-derived growth factor | Regranex | Topical | Diabetic foot ulcers |
| Pressure ulcers | |||
| Recombinant human vascular endothelial growth factor. | Telbermin | Topical | Diabetic foot ulcers |
| Recombinant human basic fibroblast growth factor. | N/A | Topical | Pressure ulcers |
Adapted from [48] with copyright permission.
| Biomaterials | Cells/Animals | Results | Reference |
|---|---|---|---|
| Chitin | Fibroblast | Chitin demonstrated no positive effects on proliferation | [50] |
| Chitin | 3T6 | Migratory process is inhibited by chitin, chitosan. | [51] |
| Chitin | HUVECs | Migratory actions were improved by chitin and chitosan | [51] |
| Chitin | Bovine PMNs | The biomaterials activated bovine poly morphonuclear cells | [51] |
| Chitin | Canine PMNs | The biomaterials activated canine poly morphonuclear cells | [52] |
| Chitin | Canine PMNs | They are induced complement-mediated chemotactic actions | [53] |
| Chitin | Canine PMNs | Supernatants of canine polymorphonuclear cells incubated with chitin | [54] |
| Chitin | Macrophage | Chitin is a size-dependent stimulator of macrophage IL-17A production and its receptor expression | [55] |
| Chitin | Dog | Numbers of MN and polymorphonuclear neutrophils cells were bigger in the chitin group than in the control group. | [56] |
| Chitin-sponge | Dog, cow, cats | Chitin-sponges were used in 30 study cases as filling agents for surgical tissue defects. | [57] |
| Chitin-cotton | Dog, cow, cats | Chitin-cotton was used in 8 cases of trauma and 12 cases of abscess as a wound dressing | [57] |
| Chitin-flake | Dog, cow, cats | Chitin-flake was used in 9 cases of trauma as a wound dressing. | [57] |
| Chitin/NWF | Dog | The quantity of PGE2 in the exudate induced by chitin was about five times as high as that in the exudate induced by chitin. | [56] |
| Chitin | Dog | Chitin activated the complement components C3 and C5, but not C4 | [58] |
Adapted from [49] with copyright permission.
| Delivery method | Results | References |
|---|---|---|
| Hydrogels | Fast-tracked wound healing by fibroblast cell proliferation from rat skin | [60] |
| Films | Chitosan species of low degree of deacetylation induce adhesion and proliferationin children foreskin keratinocytes and fibroblasts | [61] |
| Hydrogels | Rapid haemostasis in mice | [62] |
| Fast-tracked wound healing | [62] | |
| Fast-tracked wound healing | [63] | |
| Skin reconstruction following a burn on a swine skin | [64] | |
| Reduced healing time and accelerated re-epithelialization in rats | [65] | |
| Gel powder | Full-thickness of cartilage healing therapy in rabbits | [66] |
| Chronic udder trauma close to the nipples in cows | [67] | |
| Dressing material | Fast wound healing in human subjects | [68] |
| Membranes | Fast wound healing in human trials | [68] |
| Artificial skin | Total colonization by fibroblasts in human subjects | [69] |
This table was adapted from [59] with copyright permission.
Related Research Data
Disclosure statement
There is no conflict of interest in this paper.
References
- Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89:219–229. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Mardani M. An overview of the effectiveness of the most important native medicinal plants of iran on hemorrhoid based on iranian traditional medicine textbooks. J Glob Pharma Technol. 2017;8:24–26. [Google Scholar]
- Hormozi M, Assaei R, Boroujeni MB. The effect of aloe vera on the expression of wound healing factors (TGFβ1 and bFGF) in mouse embryonic fibroblast cell: in vitro. Biomed Pharmacother. 2017;88:610–616. study. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Mulder GD, Vande Berg JS. Cellular senescence and matrix metalloproteinase activity in chronic wounds. Relevance to debridement and new technologies. J Am Podiatr Med Assoc. 2002;92:34–37. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Diegelmann RF, Evans MC. Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci. 2004;9:283–289. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Hasanzadeh-kiabi F, Negahdari B. Applications of drug anesthesia in control chronic pain. J Investig Surg. 2017;32. DOI:10.1080/08941939.2017.1397230 [Taylor & Francis Online], [Web of Science ®], [Google Scholar]
- Hasanzadeh-Kiabi F. Nano-drug for pain medicine. Drug Res. (Stuttg). 2017;68. DOI:10.1055/s-0043-120661 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Gosain A, DiPietro LA. Aging and wound healing. World J Surg. 2004;28:321–326. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Ahmadvand H, Khosrowbeygi A, Shahsavari G, et al. The effects of sodium selenite on serum lipid profile and atherogenic indexes in diabetic rats. Yafteh. 2015;16:36–43. [Google Scholar]
- Hormozi M, Soltanghoraei H, Zarnani AH, et al. The effect of 5’-(N-Ethylcarboxamido) Adenosine (NECA) on angiogenesis in transplanted human ovarian tissue. Fertil Steril. 2011;95:2560–2563.e1-5. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Hanson SE, Kleinbeck KR, Cantu D, et al. Local delivery of allogeneic bone marrow and adipose tissue‐derived mesenchymal stromal cells for cutaneous wound healing in a porcine model. J Tissue Eng Regen Med. 2016;10:E90–E100. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Procházka V, Gumulec J, Jalůvka F, et al. Cell therapy, a new standard in management of chronic critical limb ischemia and foot ulcer. Cell Transplant. 2010;19:1413–1424. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Aranguren XL, Verfaillie CM, Luttun A. Emerging hurdles in stem cell therapy for peripheral vascular disease. J Mol Med. 2009;87:3–16. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Yoshikawa T, Mitsuno H, Nonaka I, et al. Wound therapy by marrow mesenchymal cell transplantation. Plast Reconstr Surg. 2008;121:860–877. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Vojtaššák J, Danišovič L, Kubeš M, et al. Autologous biograft and mesenchymal stem cells in treatment of the diabetic foot. Neuroendocrinol Lett. 2006;27:134–137. [PubMed], [Web of Science ®], [Google Scholar]
- Moghaddasi M, Hormozi M, Delfan B, et al. The effects of olive leaf extract on corticostrone and dihydroepianderestron hormones after inducing cerebral hypoperfusion in male rats. Yafte. 2015;17:42–50. [Google Scholar]
- Hormozi M, Talebi S, Hassan AZ, et al. Effect of 5′-(N-Ethylcarboxamido) adenosine (NECA) on expression of VEGF and angiopoietin in the human ovarian cortex after transplantation to nude mice. Clin Biochem. 2011;44:S287. [Crossref], [Web of Science ®], [Google Scholar]
- Park BS, Jang KA, Sung JH, et al. Adipose-derived stem cells and their secretory factors as a promising therapy for skin aging. Dermatologic Surg. 2008;34:1323–1326. [PubMed], [Web of Science ®], [Google Scholar]
- Ghaemimanesh F, Rabbani HA, Ahmadian GHR, et al. Expression profile of neurotensin receptors in ovarian cancer cell lines. Yafteh. 2013;25:474–483. [Google Scholar]
- Zarei F, Negahdari B, Eatemadi A. Diabetic ulcer regeneration: stem cells, biomaterials, growth factors. Artif Cells Nanomedicine Biotechnol. 2017;46:26–32. [Taylor & Francis Online], [Web of Science ®], [Google Scholar]
- Nambu M, Kishimoto S, Nakamura S, et al. Accelerated wound healing in healing-impaired db/db mice by autologous adipose tissue-derived stromal cells combined with atelocollagen matrix. Ann Plast Surg. 2009;62:317–321. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Ahman AM, Yan Y, Matthias N. Human adipose-derived stem cells seeded on a silk fibroin-chitosan scaffold enhance wound repair in a murine soft tissue injury model. Stem Cells. 2009;27:250–258. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Hormozi M, Hosseini GL, Javadi E, et al. Measurement Of HDL subgroups (HLD2HLD3) by two methods of electrophoresis and precipitation. 2001. [Google Scholar]
- Nambu M, Ishihara M, Nakamura S, et al. Enhanced healing of mitomycin C-treated wounds in rats using inbred adipose tissue-derived stromal cells within an atelocollagen matrix. Wound Repair Regen. 2007;15:505–510. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Kim WS, Park BS, Park SH, et al. Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory factors. J Dermatol Sci. 2009;53:96–102. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Mardani M. Wound antiseptic plants: an overview of the most important medicinal plants in iran affecting wound infections. J Glob Pharma Technol. 2016;8:18–23. [Google Scholar]
- Hormozi M. Relationship between micronutrients and biochemical factors of the milk in lactating mothers referred to Khoramabad health and treatment centers. Yafteh. 2002;3:7–12. [Google Scholar]
- Zarei F, Daraee H. Recent progresses in breast reconstruction: stem cells, biomaterials, and growth factors. Drug Res (Stuttg). 2017;68. DOI:10.1055/s-0043-122490 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Lu F, Mizuno H, Uysal C. a, et al. Improved viability of random pattern skin flaps through the use of adipose-derived stem cells. Plast Reconstr Surg. 2008;121:50–58. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Blanton MW, Hadad I, Johnstone BH, et al. Adipose stromal cells and platelet-rich plasma therapies synergistically increase revascularization during wound healing. Plast Reconstr Surg. 2009;123:56S–64S. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Delfan B, Zarei F, Iravani S, et al. Vitamin E and Omega-3, 6 and 9 combinations versus Vitamin E in the treatment of mastodynia. Jundishapur J Nat Pharm Prod. 2015;10:e18659. [Crossref], [Web of Science ®], [Google Scholar]
- Amos PJ, Kapur SK, Stapor PC, et al. Human adipose-derived stromal cells accelerate diabetic wound healing: impact of cell formulation and delivery. Tissue Eng Part A. 2010;16:1–12. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Ebrahimian TG, Pouzoulet F, Squiban C, et al. Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing. Arterioscler Thromb Vasc Biol. 2009;29:503–510. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Uysal a. C, Mizuno H, Tobita M, et al. The effect of adipose-derived stem cells on ischemia-reperfusion injury: immunohistochemical and ultrastructural evaluation. Plast Reconstr Surg. 2009;124:804–815. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Mardani M, Asadi-Samani M, Rezapour S, et al. Evaluation of bred fish and seawater fish in terms of nutritional value, and heavy metals. J Chem Pharm Sci. 2016;9:1277–1283. [Google Scholar]
- Mardani M, Mahmoud B, Moradmand JS, et al. Comparison of the descurainia sophia and levostatin effect on the ldl cholesterol reduction, a clinical trial study. J Chem Pharm Sci. 2016;9:1329–1333. [Google Scholar]
- Ghafarzadeh M, Eatemadi A. Clinical efficacy of liposome-encapsulated Aloe vera on melasma treatment during pregnancy. J Cosmet Laser Ther. 2017;19:181–187. [Taylor & Francis Online], [Web of Science ®], [Google Scholar]
- Nie C, Yang D, Xu J, et al. Locally administered Adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis. Cell Transplant. 2011;20:205–216. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Jaferian S, Soleymaninejad M, Negahdari B, et al. Stem cell, biomaterials and growth factors therapy for hepatocellular carcinoma. Biomed Pharmacother. 2017;88:1046–1053. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Lee SH, Lee JH, Cho KH. Effects of human adipose-derived stem cells on cutaneous wound healing in nude mice. Ann Dermatol. 2011;23:150–155. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Jaferian S, Soleymaninejad M, Daraee H. Verapamil (VER) enhances the cytotoxic effects of docetaxel and vinblastine combined therapy against non-small cell lung cancer cell lines. Drug Res. (Stuttg). 2017;68. DOI:10.1055/s-0043-117895 [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Huang S-P, Hsu C-C, Chang S-C, et al. Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound healing in a murine model of a full-thickness defect. Ann Plast Surg. 2012;69:656–662. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Song S-H, Lee M-O, Lee J-S, et al. Genetic modification of human adipose-derived stem cells for promoting wound healing. J Dermatol Sci. 2012;66:98–107. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Nadri S, Mahmoudvand H, Taee N, et al. Promethazine and oral midazolam preanesthetic children medication. Pediatr Emerg Car. 2018;34. DOI:10.1097/PEC.0000000000001389 [Crossref], [Web of Science ®], [Google Scholar]
- Zarei F, Negahdari B. Recent progresses in plastic surgery using adipose-derived stem cells, biomaterials and growth factors. J. Microencapsul. 2017;34:1–25. [Taylor & Francis Online], [Web of Science ®], [Google Scholar]
- Hassan WU, Greiser U, Wang W. Role of adipose-derived stem cells in wound healing. Wound Repair Regen. 2014;22:313–325. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Altman AM, Yan YS, Matthias N, et al. IFATS collection: human adipose-derived stem cells seeded on a silk fibroin-chitosan scaffold enhance wound repair in a murine soft tissue injury model. Stem Cells. 2009;27:250–258. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Barrientos S, Brem H, Stojadinovic O, et al. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen. 2014;22:569–578. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Azuma K, Izumi R, Osaki T, et al. Chitin, chitosan, and its derivatives for wound healing: old and new materials. J Funct Biomater. 2015;6:104–142. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Mori T, Okumura M, Matsuura M, et al. Effects of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro. Biomaterials. 1997;18:947–951. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Okamoto Y, Inoue A, Miyatake K, et al. Effects of Chitin/Chitosan and their Oligomers/Monomers on migrations of macrophages. Macromol Biosci. 2003;3:587–590. [Crossref], [Web of Science ®], [Google Scholar]
- Usami Y, Okamoto Y, Minami S, et al. Migration of canine neutrophils to chitin and chitosan. J Vet Med Sci. 1994;56:1215–1216. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Usami Y, Minami S, Okamoto Y, et al. Influence of chain length of N-acetyl-D-glucosamine and D-glucosamine residues on direct and complement-mediated chemotactic activities for canine polymorphonuclear cells. Carbohydr Polym. 1997;32:115–122. [Crossref], [Web of Science ®], [Google Scholar]
- Usami Y, Okamoto Y, Takayama T, et al. Chitin and chitosan stimulate canine polymorphonuclear cells to release leukotriene B4 and prostaglandin E2. J Biomed Mater Res. 1998;42:517–522. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Da Silva CA, Hartl D, Liu W, et al. TLR-2 and IL-17A in chitin-induced macrophage activation and acute inflammation. J Immunol. 2008;181:4279–4286. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Okamoto Y, Minami S, Matsuhashi A, et al. Polymeric N-Acetyl-D-Glucosamine (Chitin) induces histionic activation in dogs. J Vet Med Sci. 1993;55:739–742. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- OKAMOTO Y, MINAMI S, MATSUHASHI A, et al. Application of polymeric N-acetyl-D-glucosamine (chitin) to veterinary practice. J Vet Med Sci. 1993;55:743–747. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Minami S, Suzuki H, Okamoto Y, et al. Chitin and chitosan activate complement via the alternative pathway. Carbohydr Polym. 1998;36:151–155. [Crossref], [Web of Science ®], [Google Scholar]
- Patrulea V, Ostafe V, Borchard G, et al. Chitosan as a starting material for wound healing applications. Eur J Pharm Biopharm. 2015;97:417–426. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Ribeiro MP, Espiga A, Silva D, et al. Development of a new chitosan hydrogel for wound dressing. Wound Repair Regen. 2009;17:817–824. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Chatelet C, Damour O, Domard A. Influence of the degree of acetylation on some biological properties of chitosan films. Biomaterials. 2001;22:261–268. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Ishihara M, Ono K, Sato M, et al. Acceleration of wound contraction and healing with a photocrosslinkable chitosan hydrogel. Wound Repair Regen. 2001;9:513–521. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Ishihara M, Nakanishi K, Ono K, et al. Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process. Biomaterials. 2002;23:833–840. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Boucard N, Viton C, Agay D, et al. The use of physical hydrogels of chitosan for skin regeneration following third-degree burns. Biomaterials. 2007;28:3478–3488. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Alemdaroğlu C, Değim Z, Celebi N, et al. An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor. Burns. 2006;32:319–327. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Hoemann CD, Sun J, Légaré A, et al. Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthr Cartil. 2005;13:318–329. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Jin Y, Ling PX, He YL, et al. Effects of chitosan and heparin on early extension of burns. Burns. 2007;33:1027–1031. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Azad AK, Sermsintham N, Chandrkrachang S, et al. Chitosan membrane as a wound-healing dressing: characterization and clinical application. J Biomed Mater Res Part B Appl Biomater. 2004;69:216–222. [Crossref], [PubMed], [Web of Science ®], [Google Scholar]
- Damour O, Gueugniaud PY, Berthin-Maghit M, et al. A dermal substrate made of collagen-GA-chitosan for deep burn coverage: first clinical uses. Clin Mater. 1994;15:273–276. [Crossref], [PubMed], [Google Scholar]