Development and In Vivo Characterization of Probiotic Lysate-Treated Chitosan Nanogel as a Novel Biocompatible Formulation for Wound Healing

Wound healing is a physiological reaction to tissue injuries which plays a crucial role in replacing the destroyed tissues. Probiotics produce valuable compounds that possess antibacterial and anti-inflammatory activities, immunomodulatory effects, and angiogenesis traits leading to the promotion of wound healing. Chitosan nanostructures have versatile properties making them quickly produced into gels, scaffolds, nanoparticles, beads, and sponge structures that can be incorporated into wound healing processes. In the current study, three formulations from nanogel consisting of probiotic supernatant (Lactobacillus reuteri, Lactobacillus fermentum, and Bacillus subtilis sp. natto)-loaded chitosan nanogels were prepared from the culture of corresponding cultures. The chitosan nanogels were previously characterized by Zetasizer, FTIR, and TEM. The prepared formulations’ effectiveness and dressing activity were assessed by evaluating wound closure and histological trials in Sprague-Dawley rats. The results indicated that all probiotic lysate formulations have advantages over the wound healing process. However, Bacillus subtilis natto has a better wound healing quality, which is well known in pathology examination. The favorable effects of probiotic lysate nanogels, including the reasonable wound closing rate, good wound appearance, and satisfactory histological observation via in vivo examination, suggest it as a promising nominee for wound healing purposes.

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A Novel Effective Formulation of Bioactive Compounds for Wound Healing: Preparation, In Vivo Characterization, and Comparison of Various Postbiotics Cold Creams in a Rat Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8577116 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Nasim Golkar ◽

Yousef Ashoori ◽

Reza Heidari ◽

Navid Omidifar ◽

Seyedeh Narjes Abootalebi ◽

...

Keyword(s):

Wound Healing ◽

Bacillus Subtilis ◽

Lactobacillus Reuteri ◽

Healing Process ◽

Wound Healing Process ◽

Sprague Dawley ◽

Bioactive Substances ◽

Cold Cream ◽

Healing Property

The wound is a break in the integrity of the skin produced by injury, illness, or operation. Wound healing is an essential dynamic biological/physiological process that occurs in response to tissue damage. The huge health, economic, and social effects of wounds on patients and societies necessitate the research to find novel potential therapeutic agents in order to promote wound healing. Postbiotics, the newest member of the biotics family, are valuable functional bioactive substances produced by probiotics through their metabolic activity, which have several beneficial properties, including immunomodulatory, anti-inflammatory, antimicrobial, and angiogenesis characteristics, resulting in acceleration of wound healing. In the current study, three topical cold cream formulations containing postbiotics obtained from Lactobacillus fermentum, Lactobacillus reuteri, or Bacillus subtilis sp. natto probiotic strains were prepared. The effectiveness and wound healing activity of the developed postbiotics cold cream formulations were investigated compared to cold cream without postbiotics and no treatment via wound closure investigation, hydroxyproline content assay, and histological assessment in 25 Sprague Dawley rats divided into five groups. Interestingly, analysis of the results revealed that all three formulations containing postbiotics significantly accelerated the wound healing process. However, in general, the Bacillus subtilis natto cold cream manifested a better wound healing property. The pleasing wound healing characteristics of the topical postbiotics cold creams through the in vivo experiment suggest that formulations containing postbiotics can be considered as a promising nominee for wound healing approaches.

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N-Acetylcysteine Added to Local Anesthesia Reduces Scar Area and Width in Early Wound Healing—An Animal Model Study

International Journal of Molecular Sciences ◽

10.3390/ijms22147549 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7549

Author(s):

Wiktor Paskal ◽

Adriana M. Paskal ◽

Piotr Pietruski ◽

Albert Stachura ◽

Kacper Pełka ◽

...

Keyword(s):

Wound Healing ◽

Early Stage ◽

Healing Process ◽

Wound Healing Process ◽

Sprague Dawley ◽

Time Points ◽

Model Study ◽

Sprague Dawley Rats ◽

Animal Model Study ◽

Anesthetic Solution

The aim of the study was to evaluate if a pre-incisional N-acetylcysteine (NAC) treatment altered the process of wound healing in a rat model. The dorsal skin of 24 Sprague-Dawley rats was incised in six locations. Before the incisions were made, skin was injected either with lidocaine and epinephrine (one side) or with these agents supplemented with 0.015%, 0.03%, or 0.045% NAC (contralaterally). Photographic documentation of the wound healing process was made at 11 time points. Rats were sacrificed 3, 7, 14, or 60 days after incision to excise scars for histological analysis. They included: Abramov scale scoring, histomorphometry analysis, and collagen fiber arrangement assessment. Skin pretreated with 0.03% NAC produced the shortest scars at all analyzed time points, though this result was statistically insignificant. At this NAC concentration the scars had smaller areas on the third day and were narrower on the day 4 compared with all the other groups (p < 0.05). On day 7, at the same concentration of NAC, the scars had a higher superficial concentration index (p = 0.03) and larger dermal proliferation area (p = 0.04). NAC addition to pre-incisional anesthetic solution decreased wound size and width at an early stage of scar formation at all concentrations; however, with optimal results at 0.03% concentration.

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Efektivitas getah batang betadine (Jatropha multifida L.) terhadap penyembuhan luka pasca pencabutan gigi pada tikus Sprague-DawleyEffectiveness of betadine (Jatropha multifida L.) stem sap on the wound healing after tooth extraction in Sprague-Dawley rats

Jurnal Kedokteran Gigi Universitas Padjadjaran ◽

10.24198/jkg.v33i2.32563 ◽

2021 ◽

Vol 33 (2) ◽

pp. 145

Author(s):

Hendry Rusdy ◽

Astri Suryani Pasaribu Saruksuk ◽

Rahmi Syaflida Dalimunte ◽

Gostry Aldica Dohude

Keyword(s):

Wound Healing ◽

Tranexamic Acid ◽

Tooth Extraction ◽

Healing Process ◽

Control Group ◽

Wound Healing Process ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Jatropha Multifida ◽

Plant Sap

Pendahuluan: Pencabutan gigi merupakan prosedur yang sering dilakukan di kedokteran gigi. Setelah pencabutan gigi akan dihasilkan suatu perlukaan. Proses penyembuhan luka dapat dipercepat pada kondisi tertentu. Salah satu bahan alami yang dapat membantu proses penyembuhan luka adalah getah tanaman betadine (Jatropha multifida L.). Penelitian bertujuan untuk menganalisis efektivitas getah tanaman betadine terhadap penyembuhan luka dan terhadap tanda-tanda infeksi pasca pencabutan gigi Metode: Desain penelitian studi eksperimental laboratorium dengan rancangan penelitian post-test only control group design menggunakan 30 ekor tikus Sprague-Dawley. Teknik pengambilan sampel yaitu convenience sampling. Sampel dibagi menjadi 2 kelompok yaitu kelompok perlakuan dan kelompok kontrol. Kelompok perlakuan diberikan getah tanaman betadine dan kelompok kontrol diberikan asam traneksamat secara oral menggunakan sonde lambung. Tunggu selama 4 jam setelah pemberian getah tanaman betadine dan asam traneksamat. Anestesi pada tikus menggunakan ketamin 50 mg/kg berat badan secara intramuskular kemudian dilakukan pencabutan pada gigi tikus. Pengamatan dilakukan dengan melihat kriteria klinis pada hari 1,3,7 dan diperhatikan sampai luka sembuh serta lihat tanda-tanda infeksi. Analisis data dilakukan dengan uji normalitasShapiro Wilik. Hasil penelitian menunjukkan bahwa data berdistribusi tidak normal. Analisis data dilanjutkan menggunakan uji statistik mann whitney. Hasil: Terdapat perbedaan signifikan penyembuhan luka soket pasca pencabutan gigi setelah diberikan getah betadine dan asam traneksamat dengan nilai p=0,037 (p<0,005). Simpulan: Pemberian getah tanaman betadine terbukti lebih efektif terhadap proses penyembuhan luka soket pasca pencabutan gigi dibandingkan dengan pemberian asam traneksamat. Kata kunci: tikus Sprague-Dawley; penyembuhan luka; pencabutan gigi; getah batang betadine ABSTRACTIntroduction: Tooth extraction is a procedure often performed in dentistry. Tooth extraction will always cause injuries. However, the wound healing process can be accelerated under certain conditions. One of the natural ingredients that can accelerate the wound healing process is betadine (Jatropha multifida L.) plant sap. The study was aimed to analyzed the effect of betadine plant sap on wound healing and signs of infection after tooth extraction. Methods: Experimental laboratory study design with post-test only control group design was conducted towards 30 Sprague-Dawley rats. The sampling technique was convenience sampling. The sample was divided into two groups, the treatment group and the control group. The treatment group was administered with betadine plant sap, and the control group was administered with tranexamic acid orally using a gastric probe, then waited 4 hours after. The anaesthesia was then performed using 50 mg/kg body weight of ketamine intramuscularly. The extraction was performed after. Observations was conducted at the clinical criteria on days 1, 3, and 7 and continue to be monitored until the wound heals. Then, the signs of infection were observed. Data analysis was carried out using the Shapiro Wilk normality test. The results showed that the data was not normally distributed. Thus, data analysis was continued using the Mann Whitney statistical test. Results: The results showed a significant difference in the healing of socket wounds after tooth extraction after being administered with betadine sap and tranexamic acid with a value of p=0.037 (p<0.005). Conclusions: Administration of betadine plant sap is proven to be more effective in accelerating the healing process of socket wounds after tooth extraction than tranexamic acid. Keywords: Sprague-Dawley rats; wound healing; pencabutan gigi; getah batang betadine

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Effects of Albumin Infusion on Serum Levels of Albumin, Proinflammatory Cytokines (TNF-α, IL-1, and IL-6), CRP, and MMP-8; Tissue Expression of EGRF, ERK1, ERK2, TGF-β, Collagen, and MMP-8; and Wound Healing in Sprague Dawley Rats

International Journal of Inflammation ◽

10.1155/2020/3254017 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Arie Utariani ◽

Eddy Rahardjo ◽

David S. Perdanakusuma

Keyword(s):

Wound Healing ◽

Healing Process ◽

Serum Levels ◽

Tissue Expression ◽

Wound Healing Process ◽

Casein Diet ◽

Sprague Dawley ◽

Albumin Infusion ◽

Sprague Dawley Rats ◽

Protein Feed

In this study, we sought to determine the roles of albumin in wound healing, which is infused both pre- and postoperatively in malnourished patients presenting with hypoalbuminemia. For the purposes of the study, we used 25 male Sprague Dawley rats of predetermined weight and age, which were initially maintained in a standard environment and fed the same diet for 7 days prior to being segregated into one of the following five groups: A, control, normal protein feed (20% casein); B, hypoalbuminemia, 25% rat albumin infusion prior to surgery; C, hypoalbuminemia, normal protein feed (20% casein); D, hypoalbuminemia, 25% rat albumin infusion after surgery; and E, hypoalbuminemia, low-protein feed (casein 2%). The animals in all five groups were subjected to four deep incisions in their dorsal muscle fascia. On days 1, 3, 5, and 7 after surgery, ELISA was used to determine serum levels of TNF-α, IL-1, IL-6, CRP, and MMP-8, whereas immunohistochemistry was used to determine the tissue expression of EGFR, ERK1, ERK2, TGF-β, collagen, and MMP-8. Significant reductions in serum levels of TNF-α, IL-1, and CRP were detected in the groups receiving albumin infusion and the high-casein diet (P<0.05). The administration of albumin and a high-casein diet also increased the tissue expression of EGFR, ERK1, ERK2, TGF-β, and collagen and decreased that of MMP-8 relative to the hypoalbuminemia control (P<0.05). We propose that the administration of albumin promoted NF-κB signaling which, in turn, induced the transduction and transcription of factors involved in wound healing. Albumin infusion and dietary proteins play vital roles in accelerating the wound healing process, as they can contribute to correcting the hypoalbuminemic state. These findings provide insights that will contribute to our understanding of wound healing, particularly in malnourished patients.

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Pengaruh Aplikasi Gel Ekstrak Kulit Citrus Sinensis terhadap Epitelisasi pada Penyembuhan Luka Gingiva Tikus Sprague Dawley

Majalah Kedokteran Gigi Indonesia ◽

10.22146/majkedgiind.9012 ◽

2015 ◽

Vol 1 (1) ◽

pp. 86

Author(s):

Aqilla Tiara Kartiningtyas ◽

Prayitno Prayitno ◽

Sri Pramestri Lastianny

Keyword(s):

Wound Healing ◽

Sweet Orange ◽

Healing Process ◽

Orange Peel ◽

Control Group ◽

Wound Healing Process ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Orange Peel Extract ◽

Peel Extract

Penyembuhan luka merupakan mekanisme pertahanan jaringan, dengan epitelisasi sebagai salah satu parameternya. Kulit jeruk manis memiliki potensi dalam penyembuhan luka karena mengandung nutrisi yang memiliki peran dalam mempercepat penyembuhan luka. Penelitian ini bertujuan untuk mengetahui efek aplikasi topikal gel ekstrak kulit jerukmanis terhadap epitelisasi pada proses penyembuhan luka gingiva labial tikus Sprague Dawley. Dua puluh tujuh ekor tikus Sprague Dawley, berumur 2-3 bulan, dibagi dalam 3 kelompok, kontrol positif, perlakuan, dan kontrol negatif. Perlukaan pada gingiva labial mandibula dibuat dengan punch biopsy berdiameter 2,5 mm. Luka pada kelompok kontrolpositif diaplikasikan Aloclair, kelompok perlakuan diaplikasikan gel ekstrak kulit jeruk manis 10%, dan kelompok kontrol negatif diaplikasikan CMC-Na, masing-masing 2 kali sehari selama 1 menit secara topikal. Tiga ekor tikus dari tiap kelompok didekapitasi masing-masing pada hari ke-3, 7, dan 14. Jaringan luka diambil dan dibuat sediaan histologis dengan pengecatan Hemaktosilin Eosin. Pengukuran ketebalan epitel dilakukan dengan menggunakan Optilab yang dipasang pada mikroskop cahaya. Data ketebalan epitel dianalisis dengan menggunakan ANAVA dua jalur. Hasil pengukuran ketebalan epitel menunjukkan perbedaan yang tidak signifikan pada kelompok kontrol positif dengan perlakuan (p>0,05), namun menunjukkan perbedaan yang signifikan pada kelompok perlakuan dengan kontrol negatif (p<0,05) pada hari 3, 7, dan 14 setelah perlukaan. Kesimpulan dari penelitian ini adalah aplikasi topikal gel ekstrak kulit jeruk manis mempercepat epitelisasi pada proses penyembuhan luka gingiva labial tikus Sprague Dawley. Effect of Topical Application of Sweet Orange (Citrus sinensis) Peel Extract Gel on Epithelialization of Labial Gingival Wound Healing: In Vivo Studies in Sprague Dawley Rats. Wound healing is a defense mechanism from complex biological phenomenon, in which epithelialization occurs as one of its parameters. Sweet orange peelcontains nutrients that have role in enhancing wound healing process. The objective of this research is to determine the effect of topical application of sweet orange peel extract gel on epithelialization of wound healing process in labial mandibular gingiva of Sprague Dawley rats. Twenty seven Sprague Dawley rats were divided into 3 groups: positivecontrol, treatment, and negative control. Labial mandibular gingival was wounded using 2.5 mm diameter punch biopsy. Topically, each wound of positive control group was administered Aloclair, treatment group was administered 10% sweet orange peel extract gel, and negative control group was administered CMC-Na, twice a day for 1 minute. Three rats from each group were sacrificed for histological evaluation at 3, 7, and 14 days and the specimens were stained with HE. The measurement of the epithelial thickness used Optilab installed on microscope. The data obtained from the measurement was analyzed using two-way ANOVA. There was insignificant difference between positive control group and treatment group (p>0.05) while there was significant difference between treatment group and negative control group (p<0.05) observed at 3, 7, and 14 days. The conclusion of this research is that the application of sweet orange peel extract gel accelerates epithelialization of wound healing process in labial mandibular gingiva of Sprague Dawley rats.

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The Therapeutic Effect and In Vivo Assessment of Palmitoyl- GDPH on the Wound Healing Process

Pharmaceutics ◽

10.3390/pharmaceutics13020193 ◽

2021 ◽

Vol 13 (2) ◽

pp. 193

Author(s):

Nur Izzah Md Fadilah ◽

Mohd Basyaruddin Abdul Rahman ◽

Loqman Mohamad Yusof ◽

Noordin Mohamed Mustapha ◽

Haslina Ahmad

Keyword(s):

Wound Healing ◽

Healing Process ◽

Treated Group ◽

Biologically Active ◽

Wound Healing Process ◽

Sprague Dawley ◽

Liquid Form ◽

Control Drug ◽

Hair Follicle Growth

The standard treatment of open wounds via the direct usage of therapeutic agents is not without limitations with respect to healing. Small peptides can create a favorable milieu for accelerating the healing of wounds. This study presents the potential of a novel fatty acid conjugated tetrapeptide (palmitic acid-glycine-aspartic acid-proline-histidine; Palmitoyl-GDPH) in alleviating wound healing. Tetracycline was employed as a standard control drug following its significance in wound healing including biologically active and antimicrobial effects. The peptide in liquid form was applied on to a 4 cm2 full thickness wound surgically induced at the dorsum of Sprague Dawley (SD) rats. The in vivo wound treatment with Palmitoyl-GDPH for eighteen days, histologically demonstrated an almost perfect healing exhibited by increased re-epithelialization, enhanced collagen deposition, and diminished scar formation compared to the controls. In addition, the well-developed epidermal-dermal junction and ultimate stimulation of hair follicle-growth in the Palmitoyl-GDPH treated group indicated the wound to have healed as functionally viable tissues. In general, the much lower hemogram values in the Palmitoyl-GDPH group indicated that the ongoing healing is en route to an earlier recovery. Additionally, the liver, kidney, and pancreas function biomarkers being within normal limits indicated the relatively non-toxic nature of Palmitoyl-GDPH at the used dosage. These results indisputably supported the great potential of this newly synthesized Palmitoyl-GDPH to be used as an effective therapeutic agent for wound healing (this actually means creating a new wound).

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Single Dose of N-Acetylcysteine in Local Anesthesia Increases Expression of HIF1α, MAPK1, TGFβ1 and Growth Factors in Rat Wound Healing

International Journal of Molecular Sciences ◽

10.3390/ijms22168659 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8659

Author(s):

Wiktor Paskal ◽

Michał Kopka ◽

Albert Stachura ◽

Adriana M. Paskal ◽

Piotr Pietruski ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

Control Group ◽

Wound Healing Process ◽

Sprague Dawley ◽

Regenerative Processes ◽

Wound Site ◽

Post Surgery ◽

Sprague Dawley Rats ◽

Anesthetic Solution

In this study, we aimed to investigate the influence of N-acetylcysteine (NAC) on the gene expression profile, neoangiogenesis, neutrophils and macrophages in a rat model of incisional wounds. Before creating wounds on the backs of 24 Sprague–Dawley rats, intradermal injections were made. Lidocaine–epinephrin solutions were supplemented with 0.015%, 0.03% or 0.045% solutions of NAC, or nothing (control group). Scars were harvested on the 3rd, 7th, 14th and 60th day post-surgery. We performed immunohistochemical staining in order to visualize macrophages (anti-CD68), neutrophils (anti-MPO) and newly formed blood vessels (anti-CD31). Additionally, RT-qPCR was used to measure the relative expression of 88 genes involved in the wound healing process. On the 14th day, the number of cells stained with anti-CD68 and anti-CD31 antibodies was significantly larger in the tissues treated with 0.03% NAC compared with the control. Among the selected genes, 52 were upregulated and six were downregulated at different time points. Interestingly, NAC exerted a significant effect on the expression of 45 genes 60 days after its administration. In summation, a 0.03% NAC addition to the pre-incisional anesthetic solution improves neovasculature and increases the macrophages’ concentration at the wound site on the 14th day, as well as altering the expression of numerous genes that are responsible for the regenerative processes.

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Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

International Journal of Molecular Sciences ◽

10.3390/ijms22084087 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4087

Author(s):

Maria Quitério ◽

Sandra Simões ◽

Andreia Ascenso ◽

Manuela Carvalheiro ◽

Ana Paula Leandro ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

In Vitro Release ◽

Peptide Hormone ◽

Plga Nanoparticles ◽

Wound Healing Process ◽

Target Area ◽

Encapsulation Process

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

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In Vivo Testing of Sericin-Polyurethane Nanofiber Mats for Wound Healing in Rats

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.751.581 ◽

2017 ◽

Vol 751 ◽

pp. 581-585 ◽

Cited By ~ 1

Author(s):

Piyaporn Kampeerapappun ◽

Pornpen Siridamrong

Keyword(s):

Wound Healing ◽

Healing Process ◽

Active Agent ◽

L929 Cell ◽

Wound Healing Process ◽

Original Size ◽

Nanofiber Mats ◽

Dressing Materials

The objective of this study was to investigate sericin-polyurethane nanofiber cover (SUC) for wound dressing materials in a rat skin. Sericin-polyurethane blended nanofibers were fabricated by using electrospinning. The composition of 3%w/v polyurethane in ethanol and 19% w/v sericin were blended and electrospun at 15 kV, 20 cm from tip to collector with a feed rate of 6.2 ml/hr. The mats, approximately 1.5 mm thick, were sterile by gamma irradiation with a radiation dose of 15 kGy. The samples of in vitro and in vivo testing were separated into three groups; gauze, polyurethane nanofiber cover (UC), and SUC. In vitro cultured L929 cell lines were investigated with inverted microscope. It was found that cells migrated to SCU. For in vivo tests, the remaining wound in rats was measured on day 2-14 after excision. Compared to original size of wound samples, the size of the wound remained 24% for SUC, 33% for gauze, and 34% for UC at day 8. The sericin, an active agent, contained in SUC mats was about 5 µl at 1.5 ×1.5 cm. It can be concluded that sericin is non-toxic to cells and can promote wound healing process in rats.

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Loss of Diacylglycerol Kinase α Enhances Macrophage Responsiveness

Frontiers in Immunology ◽

10.3389/fimmu.2021.722469 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laryssa C. Manigat ◽

Mitchell E. Granade ◽

Suchet Taori ◽

Charlotte Anne Miller ◽

Luke R. Vass ◽

...

Keyword(s):

Wound Healing ◽

T Cell ◽

Healing Process ◽

Cell Activity ◽

Regulatory Function ◽

Burned Area ◽

Wound Healing Process ◽

Wound Model ◽

Complex Wound

The diacylglycerol kinases (DGKs) are a family of enzymes responsible for the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). In addition to their primary function in lipid metabolism, DGKs have recently been identified as potential therapeutic targets in multiple cancers, including glioblastoma (GBM) and melanoma. Aside from its tumorigenic properties, DGKα is also a known promoter of T-cell anergy, supporting a role as a recently-recognized T cell checkpoint. In fact, the only significant phenotype previously observed in Dgka knockout (KO) mice is the enhancement of T-cell activity. Herein we reveal a novel, macrophage-specific, immune-regulatory function of DGKα. In bone marrow-derived macrophages (BMDMs) cultured from wild-type (WT) and KO mice, we observed increased responsiveness of KO macrophages to diverse stimuli that yield different phenotypes, including LPS, IL-4, and the chemoattractant MCP-1. Knockdown (KD) of Dgka in a murine macrophage cell line resulted in similar increased responsiveness. Demonstrating in vivo relevance, we observed significantly smaller wounds in Dgka-/- mice with full-thickness cutaneous burns, a complex wound healing process in which macrophages play a key role. The burned area also demonstrated increased numbers of macrophages. In a cortical stab wound model, Dgka-/- brains show increased Iba1+ cell numbers at the needle track versus that in WT brains. Taken together, these findings identify a novel immune-regulatory checkpoint function of DGKα in macrophages with potential implications for wound healing, cancer therapy, and other settings.

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