Deep Wound Healing Research Articles

Copper-MOF and tannic acid-empowered composite cryogel as a skin substitute for accelerated deep wound healing

The effective management of deep skin wounds remains a significant healthcare challenge that often deteriorates with bacterial infection, oxidative stress, tissue necrosis, and excessive production of wound exudate. Current medical approaches, including traditional wound dressing materials, cannot effectively address these issues. There is a great need to engineer advanced and multifunctional wound dressings to address this multifaceted problem effectively. Herein, a rationally designed composite cryogel composed of a Copper Metal-Organic Framework (Cu-MOF), tannic acid (TA), polyvinyl alcohol (PVA), and zein protein has been developed by freeze-thaw technique. Cryogels display a remarkable swelling capacity attributed to their interconnected microporous morphology. Moreover, dynamic mechanical behaviour with the characteristics of potent antimicrobial, antioxidant, and biodegradation makes it a desirable wound dressing material. It was further confirmed that the material is highly biocompatible and can release TA and copper ions in a controlled manner. In-vivo skin irritation in a rat model demonstrated that composite cryogel did not provoke any irritation/inflammation when applied to the skin of a healthy recipient. In a deep wound model, the composite cryogel significantly accelerates the wound healing rate. These findings highlight the multifunctional nature of composite cryogels and their promising potential for clinical applications as advanced wound dressings.

CaO2-Cu2O micromotors accelerate infected wound healing through antibacterial functions, hemostasis, improved cell migration, and inflammatory regulation.

During the wound tissue healing process, the relatively weak driving forces of tissue barriers and concentration gradients lead to a slow and inefficient penetration of bioactive substances into the wound area, consequently showing an impact on the effectiveness of deep wound healing. To overcome these challenges, we constructed biocompatible CaO2-Cu2O "micromotors". These micromotors reacted with the fluids at the wound site, releasing oxygen bubbles and propelling particles deep into the wound tissue. In vitro experimental results revealed that these micromotors not only exhibited antibacterial and hemostatic functions but also facilitated the migration of dermal fibroblasts and vascular endothelial cells, while modulating the inflammatory microenvironment. A methicillin-resistant Staphylococcus aureus infected full-thickness-wound model was created in rats, in which CaO2-Cu2O micromotors markedly expedited the wound healing process. Specifically, CaO2-Cu2O provided a sterile microenvironment for wounds and increased the amounts of M1-type macrophages during infection and inflammation. During the proliferation and remodeling stages, the amount of M1 macrophages gradually decreased, while the amount of M2 macrophages increased, and CaO2-Cu2O did not prolong the inflammatory period. Furthermore, the introduction of a regenerated silk fibroin (RSF) film on the wound surface successfully enhanced the therapeutic effects of CaO2-Cu2O against the infected wound. The combined application of oxygen-producing CaO2-Cu2O micromotors and a RSF film demonstrates significant therapeutic potential and emerges as a promising candidate for the treatment of infected wounds.

The Significant Potential of Simonkolleite Powder for Deep Wound Healing under a Moist Environment: In Vivo Histological Evaluation Using a Rat Model.

In the present work, simonkolleite powder consisting of Zn5(OH)8Cl2·H2O composition was proposed as a new candidate material for the healing of deep wounds in a moist environment. The powder was synthesized using a solution process and evaluated for wound-healing effects in rats. The pH value of physiological saline at 37 °C using the simonkolleite powder was 7.27, which was the optimal pH value for keratinocyte and fibroblast proliferation (range: 7.2-8.3). The amount of Zn2+ ions sustainably released from simonkolleite powder into physiological saline was 404 mmol/L below cytotoxic ion concentrations (<500 mmol/L), and the rhombohedral simonkolleite was accordingly converted to monoclinic Zn5(OH)10·2H2O. To evaluate the wound-healing effect of simonkolleite powder, the powder was applied to a full-thickness surgical wound reaching the subcutaneous tissue in the rat's abdomen. The histological analysis of the skin tissues collected after 1, 2, and 4 weeks found that angiogenesis, collagen deposition, and maturation were notedly accelerated due to the Zn2+ ions released from simonkolleite powder. The simonkolleite regenerated collagen close to autologous skin tissue after 4 weeks. The hair follicles, one of the skin appendages, were observed on the regenerative skin in the simonkolleite group at 4 weeks but not in the control group. Therefore, simonkolleite was hypothesized to stimulate the early regeneration of skin tissue in a moist environment, compared with commercial wound dressing material. These results suggested that simonkolleite could offer great potential as new wound dressing material.

Can L-PRF be helpful for delayed deep wound healing after a tracheotomy or lymph node dissection in a pN0 status?: A case report

Leukocyte platelet-rich fibrin (L-PRF) is used for its ability to deliver high concentrations of autologous growth factors to host tissues, to promote tissue repair. This report describes the case of a 48-year-old woman with tongue cancer treated surgically (pT3pN0), who experienced a delay of five weeks in the process of deep wound healing after a tracheotomy and cervical lymph node dissection that was treated with L-PRF. The patient had no risk factors for delayed wound healing, except for active preoperative smoking. Several attempts were made to stimulate bleeding and edge-to-edge closure, without conclusive results. However, five days after L-PRF placement, the subcutaneous tissues were adhering to the deep planes in both wounds. Fifteen days after L-PRF treatment, a complete wound healing was observed which allowed initiation of postoperative radiotherapy. This case report questions the potential of L-PRF for patients with a pN0 status, not only in superficial wounds, but also in deep wound healing. However, the use of L-PRF for patients with a pN1 status is not recommended, given the possible presence of tumour cells in the tissues, and the activation of these tumour cells by the growth factors present in L-PRF. This report supports the idea that L-PRF can contribute to deep soft tissue healing for patients with a pN0 status due to its positive clinical healing effects.

A Preclinical Validation of Iron Oxide Nanoparticles for Treatment of Perianal Fistulizing Crohn's Disease.

Fistulizing anoperineal lesions are severe complications of Crohn’s disease (CD) that affect quality of life with a long-term risk of anal sphincter destruction, incontinence, permanent stoma, and anal cancer. Despite several surgical procedures, they relapse in about two-thirds of patients, mandating innovative treatments. Ultrasmall particles of iron oxide (USPIO) have been described to achieve in vivo rapid healing of deep wounds in the skin and liver of rats thanks to their nanobridging capability that could be adapted to fistula treatment. Our main purpose was to highlight preclinical data with USPIO for the treatment of perianal fistulizing CD. Twenty male Sprague Dawley rats with severe 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced proctitis were operated to generate two perianal fistulas per rat. At day 35, two inflammatory fistulas were obtained per rat and perineal magnetic resonance imaging (MRI) was performed. After a baseline MRI, a fistula tract was randomly drawn and topically treated either with saline or with USPIO for 1 min (n = 17 for each). The rats underwent a perineal MRI on postoperative days (POD) 1, 4, and 7 and were sacrificed for pathological examination. The primary outcome was the filling or closure of the fistula tract, including the external or internal openings. USPIO treatment allowed the closure and/or filling of all the treated fistulas from its application until POD 7 in comparison with the control fistulas (23%). The treatment with USPIO was safe, permanently closed the fistula along its entire length, including internal and external orifices, and paved new avenues for the treatment of perianal fistulizing Crohn’s disease.

In vitro evaluation of a synthetic (Biobrane®) and a biopolymer (Epicite) wound dressing with primary human juvenile and adult fibroblasts after different colonization strategies

BackgroundThe three-dimensional [3D] wound dressings Biobrane® and Epicite are used in the wound management. Fibroblasts are important for successful deep wound healing. The direct effect of Biobrane® and Epicite on human fibroblasts, particularly of juvenile individuals, remains unclear. Therefore, this study compared the survival and growth characteristics of juvenile and adult dermal fibroblasts on Biobrane® and Epicite using different culture models. MethodMurine (L929), primary juvenile and adult human fibroblasts were seeded on both materials using two dimensional (2D, slide culture) or 3D culture at the medium-air interface and dynamical rotatory culture. Cell adherence, viability, morphology, actin cytoskeleton architecture and DNA content were monitored. Scanning electron microscopy (SEM) analyses could be only performed from Biobrane®. Permeability of both materials were tested. ResultsThe majority of all tested fibroblasts species survived on both dressings with no significant differences between 1 and 14 days. Juvenile and adult fibroblasts exerted typical fibroblast morphology with spindle-shaped cell bodies on the materials. SEM visualized morphological differences between murine and human fibroblasts on Biobrane®. Juvenile and adult fibroblasts colonized Biobrane® in rotatory culture after 7 days the most. The Biobrane® rotatory culture of L929 and juvenile fibroblasts showed after 7 days the significantly highest DNA amount. No major gender differences could be observed. Biobrane® had a higher permeability than Epicite. ConclusionBoth wound dressing can be colonized by fibroblasts suggesting their high cytocompatibility. Fibroblast survival and morphology on Biobrane® and Epicite depended on the culture system and the fibroblast source.

Contribution of the Transcription Factors Sp1/Sp3 and AP-1 to Clusterin Gene Expression during Corneal Wound Healing of Tissue-Engineered Human Corneas.

In order to reduce the need for donor corneas, understanding of corneal wound healing and development of an entirely tissue-engineered human cornea (hTECs) is of prime importance. In this study, we exploited the hTEC to determine how deep wound healing affects the transcriptional pattern of corneal epithelial cells through microarray analyses. We demonstrated that the gene encoding clusterin (CLU) has its expression dramatically repressed during closure of hTEC wounds. Western blot analyses confirmed a strong reduction in the expression of the clusterin isoforms after corneal damage and suggest that repression of CLU gene expression might be a prerequisite to hTEC wound closure. Transfection with segments from the human CLU gene promoter revealed the presence of three regulatory regions: a basal promoter and two more distal negative regulatory regions. The basal promoter bears DNA binding sites for very potent transcription factors (TFs): Activator Protein-1 (AP-1) and Specificity protein-1 and 3 (Sp1/Sp3). By exploiting electrophoretic mobility shift assays (EMSA), we demonstrated that AP-1 and Sp1/Sp3 have their DNA binding site overlapping with one another in the basal promoter of the CLU gene in hCECs. Interestingly, expression of both these TFs is reduced (at the protein level) during hTEC wound healing, thereby contributing to the extinction of CLU gene expression during that process. The results of this study contribute to a better understanding of the molecular mechanisms accounting for the repression of CLU gene expression during corneal wound healing.

Impact of skeletonized harvesting of the internal thoracic artery on intrasternal microcirculation considering preparation quality.

Previous studies have demonstrated the impact of internal thoracic artery (ITA) harvesting on microcirculation in parasternal tissues. However, the impact of skeletonized ITA harvesting on intrasternal microcirculation is unknown. Intraskeletal tissue perfusion has been proven to be crucial for deep wound healing. Furthermore, the impact of different levels of surgical preparation quality on intrasternal microcirculation has not been investigated yet. Sternal microcirculation (sLDP) was monitored with a novel Laser Doppler Perfusion needle probe, while the ITA was skeletonized in a pig model. To mimic different levels of preparation quality, satellite veins were either coagulated or not during preparation. To show the effect of ideally avoiding any surgical manipulation on sLDP, the ITA was clipped in a third sham-harvested group. sLDP was reduced highly significant to 71 [standard deviation (SD): 9]% (P < 0.001) after skeletonized harvesting of the ITA. Coagulation of the satellite veins as a detrimental surgical factor resulted in a significantly stronger reduction of sLDP to 56 (SD: 11)% (P < 0.05) compared to sLDP with non-coagulated satellite veins. ITA clipping reduced sLDP highly significant to 71 (SD: 8)% (P < 0.001) in the sham-operated group. ITA harvesting markedly impairs microcirculation of the sternum but remains unavoidable when coronary artery bypass grafting should be performed. Nevertheless, excessive surgical damage and coagulation of satellite veins is avoidable and should be reduced to a minimum to minimize the risk of deep sternal wound healing complications.

Growth characteristics of human juvenile, adult and murine fibroblasts: a comparison of polymer wound dressings.

Fibroblasts are important for the successful healing of deep wounds. However, the influence exerted by Cuticell, a natural polymer on fibroblasts and by the synthetic polymer, Suprathel, made of poly-L-lactic acid, is not sufficiently characterised. This study compared the survival and growth characteristics of human juvenile and adult dermal fibroblasts as well as murine fibroblast cell line L929, on a natural polymer with those of a synthetic polymer using different culture models. Murine, juvenile and adult human fibroblasts were seeded on both the natural and synthetic polymers using statical slide culture or the medium air interface and dynamical rotatory culture. Cell adherence, viability, morphology and actin cytoskeleton architecture were monitored for 1-7 days. Biomaterial permeability was checked with a previously established diffusion chamber. The majority of the murine and adult human fibroblasts survived in slide and rotatory cultures on both wound dressings. The fibroblasts seeded on the synthetic polymer exhibited phenotypically a typical spread shape with multiple cell adhesion sites earlier than those on the natural polymer. The highest survival rates in all tested fibroblast species over the entire observation time were detected in rotatory culture (mean: >70%). Nevertheless, it led to cell-cluster formation on both materials. In the medium air interface culture, few adult fibroblasts adhered and survived until the seventh day of culture on both the natural and synthetic polymers, and no viable juvenile and L929 fibroblasts could be found by day seven. Apart from a significant higher survival rate of L929 in slide culture on the natural polymer compared with the synthetic polymer at the end of the culturing period (p<0.0001), and a higher cell survival of L929 on the natural polymer in medium air interface culture, only minor differences between both materials were evident. This suggested a comparable cytocompatibility of both materials. Permeability testing revealed slightly higher permeance of the natural polymer compared with the synthetic polymer. Cell survival rates depended on the culture system and the fibroblast source. Nevertheless, the juvenile skin fibroblasts were the most sensitive. This observation suggests that wound dressings used in treating children should be tested beforehand with juvenile fibroblasts to ensure the dressing does not compromise wound healing. Future experiments should also include the response of compromised fibroblasts, for example, from burn patients.

Recombinant Spidroins as the Basis for New Materials.

Spider web proteins are unique materials created by nature that, considering the combination of their properties, do not have analogues among natural or human-created materials. Obtaining significant amounts of these proteins from natural sources is not feasible. Biotechnological manufacturing in heterological systems is complicated by the very high molecular weight of spidroins and their specific amino acid composition. Obtaining recombinant analogues of spidroins in heterological systems, mainly in bacteria and yeast, has become a compromise solution. Because they can self-assemble, these proteins can form various materials, such as fibers, films, 3D-foams, hydrogels, tubes, and microcapsules. The effectiveness of spidroin hydrogels in deep wound healing, as 3D scaffolds for bone tissue regeneration and as oriented fibers for axon growth and nerve tissue regeneration, was demonstrated in animal models. The possibility to use spidroin micro- and nanoparticles for drug delivery was demonstrated, including the use of modified spidroins for virus-free DNA delivery into animal cell nuclei. In the past few years, significant interest has arisen concerning the use of these materials as biocompatible and biodegradable soft optics to construct photonic crystal super lenses and fiber optics and as soft electronics to use in triboelectric nanogenerators. This review summarizes the latest achievements in the field of spidroin production, the creation of materials based on them, the study of these materials as a scaffold for the growth, proliferation, and differentiation of various types of cells, and the prospects for using these materials for medical applications (e.g., tissue engineering, drug delivery, coating medical devices), soft optics, and electronics. Accumulated data suggest the use of recombinant spidroins in medical practice in the near future.

A Novel Ecm Patch Combines Human Fibroblast-Derived Matrix and Mesenchymal Stem Cells for Advanced Deep Wound Healing

Decellularized extracellular matrix (ECM)-based scaffold has been a very useful resource for effective tissue regeneration. In this study, we report a novel ECM patch that physically combines human fibroblast-derived matrix (hFDM) and polyvinyl alcohol (PVA) hydrogel. hFDM was obtained after decellularization of in vitro cultured human fibroblasts. We investigated the basic characteristics of hFDM itself using immunofluorescence (fibronectin, collagen type Ⅰ) and angiogenesis related factors analysis. Successful incorporation of hFDM with PVA produced an hFDM/PVA patch, which showed an excellent cytocompatibility with human mesenchymal stem cells (hMSCs), as assessed via cell adhesion, viability, and proliferation. Moreover, in vitro scratch assay using human dermal fibroblasts showed a significant improvement of cell migration when treated with the paracrine factors orignated from the hMSCs-incorporated hFDM. To evaluate therapeutic effect on wound healing, hMSCs were seeded on the hFDM/PVA patch and they were then transplanted into mouse full-thickness wound model. Among four experimental groups (control, PVA, hFDM/PVA, hMSC/hFDM/PVA), we found that hMSC/hFDM/PVA patch accelerated the wound closure with time. More notably, histology and immunofluorescence demonstrated that compared to normal skin tissue, hMSC/hFDM/PVA patch could lead to significantly advanced tissue regeneration, as confirmed via nearly normal epidermis thickness, skin adnexa regeneration (hair follicle), mature collagen deposition, and neovascularization. Additionally, cell tracking of pre-labelled hMSCs suggegsts the in vivo retention of transplanted cells in the wound region after transplantation of hMSC/hFDM/PVA patch. Taken together, our engineered ECM patch demonstrates a strong regeneration potential toward advanced wound healing.

Bioengineered Skin Substitutes: the Role of Extracellular Matrix and Vascularization in the Healing of Deep Wounds.

The formation of severe scars still represents the result of the closure process of extended and deep skin wounds. To address this issue, different bioengineered skin substitutes have been developed but a general consensus regarding their effectiveness has not been achieved yet. It will be shown that bioengineered skin substitutes, although representing a valid alternative to autografting, induce skin cells in repairing the wound rather than guiding a regeneration process. Repaired skin differs from regenerated skin, showing high contracture, loss of sensitivity, impaired pigmentation and absence of cutaneous adnexa (i.e., hair follicles and sweat glands). This leads to significant mobility and aesthetic concerns, making the development of more effective bioengineered skin models a current need. The objective of this review is to determine the limitations of either commercially available or investigational bioengineered skin substitutes and how advanced skin tissue engineering strategies can be improved in order to completely restore skin functions after severe wounds.

Bioengineered smart trilayer skin tissue substitute for efficient deep wound healing.

Skin substitutes for deep wound healing require meticulous designing and fabrication to ensure proper structural and functional regeneration of the tissue. Range of physical and mechanical properties conducive for regeneration of different layers of skin is a prerequisite of an ideal scaffold. However, single or bilayer substitutes, lacking this feature, fail to heal full thickness wound. Complete scar free regeneration of skin is still a big challenge. This study reports fabrication of a trilayer scaffold, from biodegradable polymers that can provide the right ambience for simultaneous regeneration of all the three layers of skin. The scaffold was developed through optimization of different fabrication techniques, namely, casting, electrospinning and lyophilisation, for obtaining a tailored trilayer structure. It has mechanical strength similar to skin layers, can maintain a porosity-gradient and provides microenvironments suitable for simultaneous regeneration of epidermis, dermis and hypodermis. A co-culture model, of keratinocytes and dermal fibroblasts, confirms the efficiency of the scaffold in supporting proliferation and differentiation of different types of cells, into organized tissue. The scaffold showed improved and expedited wound healing in-vivo. Taken together, these compelling evidences successfully established the engineered trilayer scaffold as a promising template for skin tissue regeneration in case of deep wound.

29-Year-Old Woman With Fever and Bilateral Lower Extremity Lesions

29-Year-Old Woman With Fever and Bilateral Lower Extremity Lesions

2016 TERMIS - Americas Conference and Exhibition San Diego, CA December 11-14, 2016.

Tissue Engineering Part AVol. 22, No. S1 AbstractsFree Access2016 TERMIS - Americas Conference and Exhibition San Diego, CA December 11–14, 2016Published Online:1 Dec 2016https://doi.org/10.1089/ten.tea.2016.5000.abstractsAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byPreparation and Characterization of Goat Hoof Keratin/Gelatin/Sodium Alginate Base Biofilm for Tissue Engineering Application30 December 2019 | Integrated Ferroelectrics, Vol. 202, No. 1In vitro Biological Evaluation of Small Intestinal Submucosa - Chitosan / Hyaluronic Acid Tridimensional Scaffolds as Deep Wound Healing Dressings Volume 22Issue S1Dec 2016 InformationCopyright 2016, Mary Ann Liebert, Inc.To cite this article:2016 TERMIS - Americas Conference and Exhibition San Diego, CA December 11–14, 2016.Tissue Engineering Part A.Dec 2016.S-1-S-156.http://doi.org/10.1089/ten.tea.2016.5000.abstractsPublished in Volume: 22 Issue S1: December 1, 2016PDF download

Microphase Separation and Gelation of Methylcellulose in the Presence of Gallic Acid and NaCl as an In Situ Gel-Forming Drug Delivery System.

Novel hydrogels of methylcellulose (MC) with gallic acid (GA) and NaCl were developed for an in situ gel-forming delivery system. Plain MC and GA/NaCl/MC were characterized using micro-differential scanning calorimetry (micro-DSC), rheological and turbidity methods. The gelation temperatures of MC were reduced to body temperature with adding GA/NaCl. GA and NaCl caused slightly different effects on the gelation/degelation temperatures during heating/cooling, respectively, based on the different sensitivities of these three techniques. The gelation mechanism was investigated by UV spectrophotometry, and the hydrophobic interaction between the aromatic ring of GA and MC was verified. The NaCl/MC hydrogel had smaller micropores than GA/MC and MC, indicating a greater cross-linked density. Doxycycline (DX) was loaded into the systems and demonstrated a synergistic effect of DX/GA. Both GA and DX exhibited a sustained release. The hydrogel of GA/4NaCl/MC could be potentially used for the in situ delivery of DX for deep wound healing.

Organ Repair, Hemostasis, and In Vivo Bonding of Medical Devices by Aqueous Solutions of Nanoparticles

AbstractSutures are traumatic to soft connective tissues, such as liver or lungs. Polymer tissue adhesives require complex in vivo control of polymerization or cross‐linking reactions and currently suffer from being toxic, weak, or inefficient within the wet conditions of the body. Herein, we demonstrate using Stöber silica or iron oxide nanoparticles that nanobridging, that is, adhesion by aqueous nanoparticle solutions, can be used in vivo in rats to achieve rapid and strong closure and healing of deep wounds in skin and liver. Nanoparticles were also used to fix polymer membranes to tissues even in the presence of blood flow, such as occurring after liver resection, yielding permanent hemostasis within a minute. Furthermore, medical devices and tissue engineering constructs were fixed to organs such as a beating heart. The simplicity, rapidity, and robustness of nanobridging bode well for clinical applications, surgery, and regenerative medicine.

Organ repair, hemostasis, and in vivo bonding of medical devices by aqueous solutions of nanoparticles.

Sutures are traumatic to soft connective tissues, such as liver or lungs. Polymer tissue adhesives require complex in vivo control of polymerization or cross-linking reactions and currently suffer from being toxic, weak, or inefficient within the wet conditions of the body. Herein, we demonstrate using Stöber silica or iron oxide nanoparticles that nanobridging, that is, adhesion by aqueous nanoparticle solutions, can be used in vivo in rats to achieve rapid and strong closure and healing of deep wounds in skin and liver. Nanoparticles were also used to fix polymer membranes to tissues even in the presence of blood flow, such as occurring after liver resection, yielding permanent hemostasis within a minute. Furthermore, medical devices and tissue engineering constructs were fixed to organs such as a beating heart. The simplicity, rapidity, and robustness of nanobridging bode well for clinical applications, surgery, and regenerative medicine.

Integration and Regression of Implanted Engineered Human Vascular Networks During Deep Wound Healing

The ability of vascularized constructs to integrate with tissues may depend on the kinetics and stability of vascular structure development. This study assessed the functionality and durability of engineered human vasculatures from endothelial progenitors when implanted in a mouse deep burn-wound model. Human vascular networks, derived from endothelial colony-forming cells in hyaluronic acid hydrogels, were transplanted into third-degree burns. On day 3 following transplantation, macrophages rapidly degraded the hydrogel during a period of inflammation; through the transitions from inflammation to proliferation (days 5-7), the host's vasculatures infiltrated the construct, connecting with the human vessels within the wound area. The growth of mouse vessels near the wound area supported further integration with the implanted human vasculatures. During this period, the majority of the vessels (∼60%) in the treated wound area were human. Although no increase in the density of human vessels was detected during the proliferative phase, they temporarily increased in size. This growth peaked at day 7, the middle of the proliferation stage, and then decreased by the end of the proliferation stage. As the wound reached the remodeling period during the second week after transplantation, the vasculatures including the transplanted human vessels generally regressed, and few microvessels, wrapped by mouse smooth muscle cells and with a vessel area less than 200 μm² (including the human ones), remained in the healed wound. Overall, this study offers useful insights for the development of vascularization strategies for wound healing and ischemic conditions, for tissue-engineered constructs, and for tissue regeneration.

Efficacy of chitin-PAA-GTMAC gel in promoting wound healing: animal study

Acrylic grafted chitin (chitin-PAA) was modified with glycidyltrimethylammonium chloride (GTMAC) with the aim of promoting wound healing. The chitin-PAA-GTMAC gels with different GTMAC contents were compared with the original chitin-PAA gel and Intrasite gel for their efficacy in deep wound healing of Wistar rats. Four full-thickness wounds were made on the dorsal skin of rats and then each was treated with 4 materials; chitin-PAA, chitin-PAA-GTMAC(1:4), chitin-PAA-GTMAC(1:10) and Intrasite gel. During 18 days of treatment, the wounds were visually observed and calculated for wound size using image analysis program. Skin wound tissues of sacrificed rats were processed for routine histological observation and immunohistochemistry of proliferating cell nuclear antigen (PCNA). The wounds covered with the chitin derivatives either with or without GTMAC showed a significant reduction in wound size in day 9 in comparison with day 12 for those covered with Intrasite gel. The faster rate and the better pattern of epidermal development observed in histological study as well as the higher dermal cell proliferation (PCNA expression) also demonstrated the better efficiency in wound healing of the chitin derivatives than Intrasite. The earliest epidermal development of the wounds treated with chitin-PAA-GTMAC (1:4) among the tested materials suggested the most promising of this material for the treatment of full-thickness open wound.