Biomimetic immunomodulation strategies for effective tissue repair and restoration.

Inflammation plays a central role in wound healing following injury or disease and is mediated by a precise cascade of cellular and molecular events. Unresolved inflammatory processes lead to chronic inflammation and fibrosis, which can result in prolonged wound healing lasting months or years that hampers tissue function. Therapeutic interventions mediated by immunomodulatory drugs, cells, or biomaterials, are therefore most effective during the inflammatory phase of wound healing when a pro-regenerative environment is essential. In this review, we discuss the advantages of exploiting knowledge of the native tissue microenvironment to develop therapeutics capable of modulating the immune response and promoting functional tissue repair. In particular, we provide examples of the most recent biomimetic platforms proposed to accomplish this goal, with an emphasis on those able to induce macrophage polarization towards a pro-regenerative phenotype.

Explants of intact endometrium to model bovine innate immunity and inflammation ex vivo.

PROBLEM: Bacterial infections commonly cause bovine endometritis and infertility via innate immune pathways. However, mechanistic studies using isolated cells or chopped tissue may be compromised by the disruption of endometrial architecture and release of damage-associated molecular patterns. So, this study aimed to establish an ex vivo model of intact bovine endometrium to study innate immunity and inflammation. METHOD OF STUDY: Intact bovine endometrium explants were collected using a sterile 8-mm punch biopsy and cultured ex vivo with bacteria or pathogen-associated molecules. Interleukin accumulation was measured, and tissue viability was assessed by microscopy, TdT-mediated biotin-dUTP nick-end labelling and lactate dehydrogenase assay. RESULTS: Intact endometrium explants accumulated IL-6, IL-1ß and IL-8 in response to Gram-negative or Gram-positive bacteria, and their purified pathogen-associated molecules; inflammatory responses were dependent on the stage of oestrous cycle. Explants of intact endometrium maintained viability and tissue architecture, and had lower basal accumulation of interleukins compared with explants using chopped endometrium. CONCLUSION: This study established a tractable ex vivo model of intact endometrium to explore the mechanisms of immunity and inflammation in the bovine endometrium.