From Inflammation to Current and Alternative Therapies Involved in Wound Healing

Serra, Mônica da Costa; Barroso, Wermerson Assunção; Silva, Neemias Neves da; Silva, Selma do Nascimento; Borges, Antônio Carlos Romão; Abreu, Iracelle Carvalho; Borges, Marilene Oliveira da Rocha

doi:10.1155/2017/3406215

Cited by 143 publications

(131 citation statements)

References 207 publications

(210 reference statements)

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“…Table 2 summarizes the parameters used to simulate acute wound healing dynamics in a bacterial system. Table 2 and ODEs in equations (1)(2)(3)(4)(5)(6)(7)(8).…”

Section: Wound Healing Design Strategymentioning

confidence: 99%

“…Acute healing is classically defined by four consecutive phases distinct in function and histological characteristics: the hemostasis phase involving blood coagulation, the inflammatory phase in which the wound is debrided of foreign material, the proliferation phase when granulation tissue forms and the wound closes, and finally the remodelling phase which includes improving the tensile strength of the wound [2]. Together, the phases demonstrate relay-like dynamics of cellular densities and functions, coordinated by the secretion of various signals [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Bacterial Controller Aided Wound Healing: A Case Study in Dynamical Population Controller Design

Green

Ren

et al. 2019

Preprint

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Wound healing is a complicated biological process consisting of many types of cellular dynamics and functions regulated by chemical and molecular signals. Recent advances in synthetic biology have made it possible to predictably design and build closed-loop controllers that can function appropriately alongside biological species. In this paper we develop a simple dynamical population model mimicking the sequential relay-like dynamics of cellular populations involved in the wound healing process. Our model consists of four nodes and five signals whose parameters we can tune to simulate various chronic healing conditions. We also develop a set of regulator functions based on type-1 incoherent feed forward loops (IFFL) that can sense the change from acute healing to incomplete chronic wounds, improving the system in a timely manner. Both the wound healing and type-1 IFFL controller architectures are compatible with available synthetic biology experimental tools for potential applications.

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“…Table 2 summarizes the parameters used to simulate acute wound healing dynamics in a bacterial system. Table 2 and ODEs in equations (1)(2)(3)(4)(5)(6)(7)(8).…”

Section: Wound Healing Design Strategymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bacterial Controller Aided Wound Healing: A Case Study in Dynamical Population Controller Design

Green

Ren

et al. 2019

Preprint

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“…Without appropriate regulation of their activity, macrophages can drive the initiation and progression of many diseases 7,8 . In particular, loss of regulation can lead to insufficient pro-inflammatory activity, leading to incomplete clearance of pathogens and/or tissue debris, impaired pro-regenerative response, chronic inflammation, and infection 6,9,18 . Recent efforts to regulate dysfunctional macrophages have focused on cell-based therapies, such as delivery of mesenchymal stem cells (MSCs) or macrophages conditioned ex vivo toward anti-inflammatory and pro-regenerative "M2" phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Experimental control of macrophage pro-inflammatory dynamics using predictive models

Weinstock

Forsmo

Wilkinson

et al. 2019

Preprint

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Macrophage activity is a major component of the healthy response to infection and injury that consists of tightly regulated early pro-inflammatory activation followed by anti-inflammatory and regenerative activity. In numerous diseases, however, macrophage polarization becomes dysregulated and can not only impair recovery, but can also promote further injury and pathogenesis, e.g. after injury, in diabetes, or in Alzheimer's disease. Dysregulated macrophages may either fail to polarize or become chronically polarized, resulting in increased production of cytotoxic factors, diminished capacity to clear pathogens, or failure to promote tissue regeneration.In these cases, a method of predicting and dynamically controlling macrophage polarization will enable a new strategy for treating diverse inflammatory diseases. In this work, we developed a model-predictive control framework to temporally regulate macrophage polarization. Using RAW 264.7 macrophages as a model system, we enabled temporal control by identifying transfer function models relating the polarization marker iNOS to exogenous pro-and anti-inflammatory stimuli. These stimuli-to-iNOS response models were identified using linear autoregressive with exogenous input terms (ARX) equations and were coupled with nonlinear elements to account for experimentally identified supra-additive and hysteretic effects. Using this model architecture, we were able to reproduce experimentally observed temporal iNOS dynamics induced with lipopolysaccharides (LPS) and interferon gamma (IFN-γ). Moreover, the identified model enabled the design of time-varying input trajectories to experimentally sustain the duration and magnitude of iNOS expression. By designing transfer function models with the intent to predict cell behavior, we were able to predict and experimentally obtain temporal regulation of iNOS expression using LPS and IFN-γ from both naïve and non-naïve initial states. Moreover, our data driven models revealed decaying magnitude of iNOS response to LPS stimulation over time that could be recovered using combined treatment with both LPS and IFN-. Given the importance of dynamic tissue macrophage polarization and overall inflammatory regulation to a broad number of diseases, the temporal control methodology presented here will have numerous applications for regulating immune activity dynamics in chronic inflammatory diseases.3

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“…The healing process of wounds has different stages, starting from the bedsores to the restoration of the damaged tissue. These stages are hemostasis, inflammation, proliferation, epithelialization, and scar maturation (repair) [4, 5]. …”

Section: Introductionmentioning

confidence: 99%

Characterization of the Cicatrization Process in Diabetic Foot Ulcers Based on the Production of Reactive Oxygen Species

Delis

Rosa

Souza

et al. 2018

Journal of Diabetes Research

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The present study aims at evaluating the correlation between the free radical formation and the healing action of lower limbs' ulcers in a randomized controlled trial with the use of an adhesive derived from natural latex associated with a light-emitting diode (LED) circuit. The sample consists of 15 participants with lower limb lesions divided into three groups: group 1 case (5 participants) received the proposed dressing system adhesive of the natural latex associated with the LED circuit; group 2 control (5 participants) received the dressings at home performed by nurses according to and established by the clinic of wounds (treated with calcium alginate or silver foam); and group 3 (5 participants) also received the dressing in their homes with the use of the dressing adhesive derived from the natural latex associated with the LED circuit. The collected data were analyzed qualitatively and quantitatively by electron paramagnetic resonance for determination of free radical formation. Kruskal-Wallis statistical test was used to evaluate the effect of treatment on the lower limb's ulcer cicatrization process and its correlation with free radical. The results obtained corroborated the hypothesis about the reduction of the quantity of these molecules in the end of treatment related to the healing wound.

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From Inflammation to Current and Alternative Therapies Involved in Wound Healing

Cited by 143 publications

References 207 publications

Bacterial Controller Aided Wound Healing: A Case Study in Dynamical Population Controller Design

Bacterial Controller Aided Wound Healing: A Case Study in Dynamical Population Controller Design

Experimental control of macrophage pro-inflammatory dynamics using predictive models

Characterization of the Cicatrization Process in Diabetic Foot Ulcers Based on the Production of Reactive Oxygen Species

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