Monika Kozak Ljunggren

Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation

Extracellular matrix proteins like collagen promote regeneration as implants in clinical studies. However, collagens are large and unwieldy proteins, making small functional peptide analogs potenti ...

Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae

Background Cysteine proteinases of Fasciola hepatica are important candidates for vaccine antigens because of their role in fluke biology and host-parasite relationships. In our previous experiments, we found that a recombinant cysteine proteinase cloned from adult F. hepatica (CPFhW) can protect rats against liver fluke infections when it is administered intramuscularly or intranasally in the form of cDNA. We also observed considerable protection upon challenge following mucosal vaccination with inclusion bodies containing recombinant CPFhW produced in Escherichia coli. In this study, we explore oral vaccination, which may be the desired method of delivery and is potentially capable of preventing infections at the site of helminth entry. To provide antigen encapsulation and to protect the vaccine antigen from degradation in the intestinal tract, transgenic plant-based systems are used. Methodology In the present study, we aimed to evaluate the protective ability of mucosal vaccinations of 12-week-old rats with CPFhW produced in a transgenic-plant-based system. To avoid inducing tolerance and to maximise the immune response induced by oral immunisation, we used the hepatitis B virus (HBV) core protein (HBcAg) as a carrier. Animals were immunised with two doses of the antigen and challenged with 25 or 30 metacercariae of F. hepatica. Conclusions We obtained substantial protection after oral administration of the plant-produced hybrids of CPFhW and HBcAg. The highest level of protection (65.4%) was observed in animals immunised with transgenic plants expressing the mature CPFhW enzyme flanked by Gly-rich linkers and inserted into c/e1 epitope of truncated HBcAg. The immunised rats showed clear IgG1 and IgM responses to CPFhW for 4 consecutive weeks after the challenge.

Optimisation of conductive polymer biomaterials for cardiac progenitor cells

The characterisation of biomaterials for cardiac tissue engineering applications is vital for the development of effective treatments for the repair of cardiac function. New ‘smart’ materials developed from conductive polymers can provide dynamic benefits in supporting and stimulating stem cells via controlled surface properties, electrical and electromechanical stimulation. In this study we investigate the control of surface properties of conductive polymers through a systematic approach to variable synthesis parameters, and how the resulting surface properties influence the viability of cardiac progenitor cells. A thorough analysis investigating the effect of electropolymerisation parameters, such as current density and growth, and reagent variation on physical properties provides a fundamental understanding of how to optimise conductive polymer biomaterials for cardiac progenitor cells.

Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants

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Stimulation of Tendon Healing With Delayed Dexamethasone Treatment Is Modified by the Microbiome

Background: The immune system reflects the microbiome (microbiota). Modulation of the immune system during early tendon remodeling by dexamethasone treatment can improve rat Achilles tendon healing. The authors tested whether changes in the microbiota could influence the effect of dexamethasone treatment. Hypothesis: A change in microbiome would influence the response to dexamethasone on regenerate remodeling, specifically tendon material properties (peak stress). Study Design: Controlled laboratory study. Methods: Specific opportunist and pathogen-free female rats were housed separately (n = 41) or together with specific pathogen-free rats carrying opportunistic microbes such as Staphylococcus aureus (n = 41). After 6 weeks, all co-housed rats appeared healthy but now carried S aureus. Changes in the gut bacterial flora were tested by API and RapID biochemical tests. All rats (clean and contaminated) underwent Achilles tendon transection under aseptic conditions. Flow cytometry was performed 8 days postoperatively on tendon tissue. Sixty rats received subcutaneous dexamethasone or saline injections on days 5 through 9 after transection. The tendons were tested mechanically on day 12. The predetermined primary outcome was the interaction between contamination and dexamethasone regarding peak stress, tested by 2-way analysis of variance. Results: Dexamethasone increased peak stress in all groups but more in contaminated rats (105%) than in clean rats (53%) (interaction, P = .018). A similar interaction was found for an estimate of elastic modulus (P = .021). Furthermore, dexamethasone treatment reduced transverse area but had small effects on peak force and stiffness. In rats treated with saline only, contamination reduced peak stress by 16% (P = .04) and elastic modulus by 35% (P = .004). Contamination led to changes in the gut bacterial flora and higher levels of T cells (CD3+CD4+) in the healing tendon (P < .05). Conclusion: Changes in the microbiome influence tendon healing and enhance the positive effects of dexamethasone treatment during the early remodeling phase of tendon healing. Clinical Relevance: The positive effect of dexamethasone on early tendon remodeling in rats is strikingly strong. If similar effects could be shown in humans, immune modulation by a few days of systemic corticosteroids, or more specific compounds, could open new approaches to rehabilitation after tendon injury.