Cutaneous wound healing could be distinguished into two main types: embryonic and adult. Embryonic healing in contrast to adult is faster, scar-less and consists of early, middle, and late phases. Actin ring is formed during the early phase and its cables pull the edges of the wound towards apposite sites during the following middle phase. De novo expression of healing specific genes is initiated also during middle phase. However, process of the wound healing continues under the closed wound in the late phase which has been poorly described. Adult wound healing is more complex, longer, and is divided into 4 phases: haemostasis, inflammation, proliferation, and remodelling phase. Adult wound healing might end with the scar. Pivotal role in the wound healing is given to matrix metalloproteinases (MMPs). These remodelling enzymes are important for releasing cytokines, inducing apoptosis, and degradation of extracellular matrix. Our laboratory performed temporal RNA-sequencing of the healing tissue using tailbud stage and swimming tadpole embryos. Results showed predominant expression of four mmps: mmp1.L, mmp7.S, mmp8.S, and mmp9.L. Injury or amputation caused the upregulation and their expression level peaked at 3-6 hours post injury which corresponds with late phase of healing. Thus, I focused on...

<p>The mechanical behavior of tissues at the macroscale is tightly coupled to cellular activity at the microscale and tuned by microstructure at the mesoscale. Dermal wound healing is a prominent example of a complex system in which multiscale mechanics regulate restoration of tissue form and function. In cutaneous wound healing, a fibrin matrix is populated by fibroblasts migrating in from a surrounding tissue made mostly out of collagen. Fibroblasts both respond to mechanical cues such as fiber alignment and stiffness as well as exert active stresses needed for wound closure. </p> <p>To model wound healing mechanobiology, we first develop a multiscale model with a two-way coupling between a microscale cell adhesion model and a macroscale tissue mechanics model. Starting from the well-known model of adhesion kinetics proposed by Bell, we extend the formulation to account for nonlinear mechanics of fibrin and collagen and show how this nonlinear response naturally captures stretch-driven mechanosensing. We then embed the new nonlinear adhesion model into a custom finite element implementation of tissue mechanical equilibrium. Strains and stresses at the tissue level are coupled with the solution of the microscale adhesion model at each integration point of the finite element mesh. In addition, solution of the adhesion model is coupled with the active contractile stress of the cell population. The multiscale model successfully captures the mechanical response of biopolymer fibers and gels, contractile stresses generated by fibroblasts, and stress-strain contours observed during wound healing. We anticipate this framework will not only increase our understanding of how mechanical cues guide cellular behavior in cutaneous wound healing, but will also be helpful in the study of mechanobiology, growth, and remodeling in other tissues. </p> <p>Next, we develop another multiscale model with a bidirectional coupling between a microscale cell adhesion model and a mesoscale microstructure mechanics model. By mimicking the generation of fibrous network in experiment, we established a discrete fiber network model to simulate the microstructure of biopolymer gels. We then coupled the cell adhesion model to the discrete model to obtain the solution of microstructure equilibrium. This multiscale model was able to recover the volume loss of fibrous gels and the contraction from cells in the networks observed in experiment. We examined the influence of RVE size, stiffness of single fibers and stretch of the gels. We expect this work will help bridge the activity of cell to the microstructure and then to the tissue mechanics especially in wound healing. We hope this work will provide more rigorous understanding in the study of mechanobiology.</p> <p>At last, we established a computational model to accurately capture the mechanical response of fibrin gels which is a naturally occurring protein network that forms a temporary structure to enable remodeling during wound healing and a common tissue engineering scaffold due to the controllable structural properties. We formulated a strategy to quantify both the macroscale (1–10 mm) stress-strain response and the deformation of the mesoscale (10–1000 microns) network structure during unidirectional tensile tests. Based on the experimental data, we successfully predict the strain fields that were observed experimentally within heterogenous fibrin gels with spatial variations in material properties by developing a hyper-viscoelastic model with non-affined evolution under stretching. This model is also potential to predict the macroscale mechanics and mesoscale network organization of other heterogeneous biological tissues and matrices.</p>

No description available.

Syftet med denna litteraturstudie är att jämföra larvterapi och konventionella metoder vid behandling av svårläkta sår utifrån följande perspektiv: upprensning av sår, duration av sårläkning och patienternas upplevelse. Polit & Becks (2006) modell användes vid arbete med denna litteraturstudie. Sökning av relevant litteratur gjordes i tre databas: PubMed, CINAHL och The Cochrane Library. Relevanta artiklar granskades med hjälp av granskningsprotokollerna modifierade av författarna efter Willman (2006). Nio olika studier har undersökts i denna litteraturstudie. Studierna utreder dels larvterapins effektivitet i upprensning av sår samt larvernas läkningsförmåga och dels hur patienterna upplever larvterapi. Detta sattes i relation till konventionella behandlingsmetoder. Resultaten är positiva i larvterapins favör. Larvterapi är ett effektivt sätt att rensa upp nekrotisk och inflammerad vävnad i svårläkta sår. Såren rensas och läker fortare med få biverkningar jämfört med konventionella behandlingar. Dessutom bildas granulationsvävnad snabbare, vilket är en förutsättning för sårets läkning. Korrekt information och involvering av patienten skapar en positiv attityd i denna behandlingsform. Ett stort behov finns för detta i sårläkningens område pga ökade restriktioner av antibiotikaanvändning och ett önskat minskat lidande hos patienter med svårläkta sår. Det finns stora möjligheter för larvterapin om den fortsätter att utforskas. / The aim of this literature study is to compare larva therapy and conventional methods in treatment of ulcers on the basis of the following perspective: debridement of ulcers, duration of wound healing and patients´ experience. Polit & Becks (2006) model was used when working with this literature study. Search of relevant literature was done in three databases: PubMed, CINAHL and The Cochrane Library. Relevant articles were checked with the help of checklists modified of authors after Willman (2006). Nine different studies have been examined. The studies partly investigate the larva therapy’s effectiveness in debridement of ulcers and maggots´ capability in healing and partly how patients experience the larva therapy. This was set in relation to conventional treatment methods. The results are positive in larva therapy’s favour. Ulcers are debrided and healed quicker with few secondary effects compared to conventional treatments. Larva therapy is an effective way to debride necrotic and inflamed tissue in ulcers. Moreover new granulation tissue forms faster which is a condition for wound healing. Correct information and patients´ participation creates a positive attitude for this treatment. There is a big need for this in wound healing because of increased restrictions of use of antibiotics and desired decreased suffering for patients with ulcers. There are many possibilities with larva therapy if it continues to be researched.

Honungens terapeutiska egenskaper utgör en grund för dess användning vid behandling av svårläkta sår vilket kan vara ett alternativ till andra konventionella metoder. Syftet med föreliggande studie var att undersöka vetenskaplig litteratur för att belysa vilka effekter användning av honung kan ha i samband med svårläkta sår samt patienters tillfredställelse med behandlingen. En systematisk modell med sju steg användes som metod för denna studie. Litteratursökningen genomfördes i databaserna PubMed, CINAHL, Medline och Cochrane Library. Relevanta artiklar granskades med hjälp av protokoll modifierad av författarna. Resultatet av 8 inkluderade studier (9 artiklar) visar att behandling med honung möjligtvis är likvärdig konventionell behandling vid svårläkta bensår. Mer forskning av hög kvalitet behövs för att säkert fastställa effektiviteten avseende behandling med honung.Nyckelord: honung, komplementär medicinsk behandling, litteraturstudie, svårläkta bensår, sårläkning. / Therapeutic properties of honey forms a basis for its use in the treatment of recalcitrant wounds which can be an alternative to other conventional methods. The purpose of this study was to examine the scientific literature to illustrate which effects the use of honey may be associated with regarding ulcers and patients' experience of treatment. A systematic model with seven stages was used as a method for this study. The literature search was conducted in PubMed, CINAHL, Medline and the Cochrane Library. Relevant articles were reviewed according to protocol modified by the authors. The results of the eight included studies (nine articles) show that honey is probably equal treatment to other conventional treatments for healing of recalcitrant leg wounds. More high quality research is needed to evaluate the effectiveness of honey treatment. Keywords: honey, complementary medical treatment, literature review, recalcitrant leg ulcers, wound healing.

No description available.

Controlled cell assembly is essential for fabricating in vitro models that mimic native tissue architecture. Conventional tissue engineering techniques are time-consuming and offer limited control over the spatial organization of cells within the assembled cell aggregates. We describe a label-free, scaffold-free, rapid cell manipulation technique to assemble cells into layered aggregates. Suspensions of cells in a culture medium with higher magnetic susceptibility are seeded into wells of a 96-well plate placed on a quartet magnet array. An FDA-approved paramagnetic agent is added to the regular cell culture medium to enhance the magnetic susceptibility. The inhomogeneous magnetic field and the susceptibility difference drive cells toward the lowest magnetic field region on the well surface. Two cell types are sequentially added to the wells to form layer-on-layer aggregates within 6 h. Next, the label-free technique is extended to develop a cell migration assay. Besides being time-consuming, the traditional scratch-based cell migration assay is not reproducible, whereas the alternate physical barrier-based method is expensive. Annular aggregates of human bronchial epithelial cells (HBEC3 KT) are formed within 3 h using a coaxially arranged ring-cylinder magnet array. The effects of the paramagnetic agent on cell viability, metabolism, and transcriptional profiles are investigated. The closures of the circular cell-free areas enclosed by HBEC3 KT are analyzed at different times in response to various signaling molecules and surface conditions. Further, we demonstrate the formation of the annular aggregates on human lung fibroblast-laden collagen hydrogel surfaces. The cell-free area closures on hydrogel surfaces in response to signaling molecules are analyzed. The high reproducibility and scalability of the label-free method make it amenable for preclinical research. / Thesis / Doctor of Philosophy (PhD) / Cell cultures are essential tools for studying cell functions under controlled conditions. A better understanding of cell behavior in tissues is required to develop effective treatments for diseases. The organized arrangement of cells in tissues controls tissue functions. The existing culture techniques are time-consuming and have limited control over the cellular arrangement. We describe a simple, rapid, and inexpensive bioprinting technique to arrange cells in layers, which resembles the cellular organization in tissues, such as the skin. The layered structures are formed in standard well plates within 6 h. Cell movement is an essential cell function in various biological processes, such as wound healing. Using the bioprinting method, we form ring-shaped cellular structures within 3 h to study cell movements in response to various signals. The ring structures enclose cell-free areas, which are populated over time as the cells move from the ring into the cell-free regions. The bioprinting method is easy to use and can rapidly form organized cellular structures for drug testing.

Traditional methods for dermal wound closure such as sutures and staples are invasive and can result in soft tissue trauma, increasing the likelihood of localized inflammation and infections. Alternately, while tissue adhesive alternatives can effectively seal and adhere to the wounds, they can also present safety concerns relating to immunogenic responses and tissue toxicity. Herein, we fabricate injectable, adhesive, and cytocompatible poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA)-dopamine (DA) hydrogels co-crosslinked via hydrazone and self-polymerized dopamine crosslinks that exhibit high water retention, improved tissue adhesiveness, and effective tissue regeneration properties. POEGMA-DA hydrogels exhibit independently tunable gelation properties based on their dual crosslinking mechanism, allowing for gelation as fast as 24 s (allowing for injection and rapid filling of irregularly-shaped wounds) while achieving relevant compressive moduli of up to 37 kPa and in vitro skin adhesion strengths of up to 1.2 kPa. The POEGMA-DA hydrogels induced no significant inflammation while demonstrating high interfacial adhesiveness in a stented skin excisional mouse model, enabling efficient dermal tissue regeneration by supporting collagen remodelling and enabling the regeneration of hair follicles, sebaceous glands, and blood vessels at the excision site over the 14-day study timeline. As such, injectable POEGMA-DA hydrogels represent a relevant non-toxic and adhesive alternative wound closure system for treating deep dermal wounds. / Thesis / Master of Applied Science (MASc) / Effective wound healing and subsequent tissue regeneration after a physical injury requires a moist sterile environment, the presence of oxygen, nutrients and enzymes, an efficient blood supply to the wound site, and a controlled inflammatory response to initiate the healing process. External methods of closing the wound to prevent infection aid in faster healing like sutures, staples, and liquid sealants which can result in infections and/or the stimulation of an inflammatory response that can hinder tissue restoration. Hydrogels, water-swellable polymer networks, represent an alternative solution that can both suppress infection while simultaneously promoting wound healing. Hydrogels have a similar structure to soft tissues like skin and can thus provide a supportive environment for cells to promote tissue regeneration and restore tissue structure and function. The swelling of hydrogels in water is highly beneficial for providing moisture at the wound site; however, this high degree of water retention also means they have a hard time sticking to tissues. To address this challenge, hydrogels can be modified with a component naturally derived from marine mussels that allows them to stick to their wet habitats, helping hydrogels to stick to the wound site while healing. In this thesis, mussel-inspired hydrogels are designed and can spontaneously gel and stick to a wound site to accelerate the restoration of the structure and function of skin. These biodegradable and injectable hydrogels are effective in accelerating wound closure with minimal evidence of scarring while suppressing negative inflammatory reactions and restoring the structure of skin by promoting the regeneration of hair follicles, sebaceous glands and blood vessels.

Bakgrund: Svårläkta bensår är ett omfattande och komplext problem inom vård och omsorg. Läkningsprocessen är ofta långdragen och innebär ett stort lidande för patienten med negativ inverkan på livskvaliteten. Faktorer som kan påverka sårläkningsprocessen med fokus på nutrition och dess inflytande på sårläkningen vid bensår har studerats i denna litteraturstudie. Syfte: Syftet var att beskriva nutritionens betydelse för läkning av bensår. Metod: En beskrivande litteraturstudie där resultatet inkluderar 15 artiklar med kvantitativ ansats. Artiklar söktes systematiskt genom databasen PubMed, varav två artiklar hittades via manuell sökning. Huvudresultat: Bensårspatienter föreligger risk för undernäring trots övervikt eller fetma och undernäring är ett vanligt förekommande. Det påvisas ett samband mellan risk för undernäring och sårtillslutningshastighet. Negativ association påvisades gällande sårläkningsprocessen vid brist på D-vitamin, C-vitamin, A-vitamin, zink, protein och albumin. Bensårspatienter som fick näringstillskott fick ett ökat intag av flera näringsämnen och ett positivt samband associeras med sårläkningsprocessen. Ett tudelat resultat huruvida järn påverkade bensårspatienterna tas i beaktande då en del patienter visade en överlag hög järnkonsumtion medan vissa patienter påvisade sig ha en allvarligt minskad nivå av järn i plasma. Slutsats: Resultatet i denna litteraturstudie ger en tydlig indikation på att näringsintaget spelar en väsentlig roll vid läkning av bensår. Samband mellan olika näringsbristtillstånd och försämrad sårläkning framkommer, trots att tillgänglig forskning idag är bristfällig. Det påvisas lyckade resultat gällande näringstillskott till bensårspatienter för att behandla/förebygga brister av olika näringsämnen, vilket har resulterat i en mer framgångsrik sårläkning. / Background: Difficult-to-heal leg ulcers are an extensive and complex problem in healthcare. The healing process is long and involves suffering for the patient with a negative impact on their quality of life. This literature review studied factors that can influence the wound healing process with a focus on nutrition and its influence on wound healing in leg ulcers. Purpose: The aim was to describe the importance of nutrition for the healing of leg ulcers. Method: A descriptive literature study where the result contains 15 articles with quantitative approaches. Articles were systematically searched through the database PubMed, of which two articles were found by manual search. Main results: Leg ulcer patients are at risk for undernourishment despite being overweight or obese, and malnutrition is a common occurrence. A relationship between the risk for undernourishment and wound closure rate is demonstrated. A negative association was demonstrated regarding the wound healing process and deficiency of vitamin D, vitamin C, vitamin A, zinc, protein and albumin was demonstrated. Leg ulcer patients who received nutritional supplements increased the intake of several nutrients and a positive relationship is associated with the wound healing process. A two-sided result whether iron affected the leg ulcer patients is taken into account as some patients showed an overall high iron consumption while some patients were shown to have a severely reduced level of iron in plasma. Conclusion: The results of this literature study gave a clear indication that nutritional intake plays an essential role in the healing of leg ulcers. Connections between various nutritional deficiency states and impaired wound healing are emerging, despite the fact that the research available today is insufficient. Successful results have been demonstrated regarding nutritional supplementation to leg ulcer patients to treat/prevent deficiencies of various nutrients, which resulted in successful wound healing.

Chronic wound healing can be seriously impeded by the formation of biofilms, infections, peri-wound edema, hematoma, osteomyelitis, and the formation of reactive oxidative species (ROS). We hypothesize that a scaffold created from Silver-Doped Nanoceria (AgCNP) embedding silk can be beneficial to aid the wound healing process, inhibit inflammation and prevent microorganisms from forming a biofilm over the wound. Current wound healing methods such as intradermal injections are not advantageous to use since they can cause unwanted responses elsewhere in the body other than the wound site. Silk, however, has a positive impact on the wound healing effect and can be used as an alternative delivery method to deliver the drugs to the target site rather than intradermal injections since its degradability is controllable and it is bioresorbable, therefore it can get absorbed by the body and degrade safely without causing bodily harm. AgCNPs are used as they have antimicrobial/antioxidant properties to scavenge harmful ROS species at the wound site and can also modify silk for UV protection. As silk's degradability can be controlled, our experiment will involve collecting data on release studies conducted in vitro to see how long it takes for the silk patch to release the drugs. Our goal is to ensure the drug is not released immediately but rather over a longer controlled time manner to protect the wound while healing.