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Research Unit 2165

The Research Unit 2165 Regeneration in Aged Individuals: Using Bone Healing as a Model System to Characterise Regeneration under Compromised Conditions aims to understand the basic mechanisms that impede the otherwise effective healing process along the two pathways of early immune response and restoration of mechanical competence through aging.  

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The field of regenerative medicine aims at restoring the original structure and function of cells and tissues in order to re-establish endogenous tissue integrity. A number of therapeutic strategies are currently under development and being evaluated in pre-clinical models or clinical trials. However, such innovative therapies are mainly needed to treat patient groups where healing conditions are impaired, such as in aged patients. Thus, with the expansion of aged populations, these therapies need to be assessed for their ability to specifically address the needs of this particular patient group. It is therefore mandatory for the field of regenerative medicine to understand the basic mechanisms of how healing in general is altered by immunological and mechanical constraints in aged patients and patients with age-related diseases. Importantly, conditions that represent positive stimuli in young patients can manifest as negative stress factors in aged patients. An optimal treatment strategy for the elderly can only exist when a profound understanding of the underlying mechanisms has been achieved.

In contrast to all other tissues of the human body, bone has a rare and unique feature: it is capable of re-establishing its initial structure and function by means of endogenous healing cascades. Despite this extraordinary feature, bone regeneration is also prone to failure due to its complexity. In a number of critical clinical cases of elderly patients the impaired healing is further exacerbated, such as in immune-compromised patients or in patients that have a deficiency in their mechano-adaptive capacity. In these cases, the endogenous healing cascade is disturbed and these mechanisms are interlinked and influence one another, which may in certain clinical cases lead to an additive or synergistic impairment of the healing process. Also metabolic conditions such as diabetes/insulin resistance and obesity with a very high prevalence in aged patients should be taken into account in this respect. It was the aim of this Research Unit to further unravel the mechanisms that hamper an otherwise effective healing process along the two cascades of immune response and mechanical competence by means of aging/compromised conditions.

The overall goal of FOR 2165 was to investigate the influence of aging on the bone healing processes from the sub-cellular to the organ level, by focusing on well-characterized mechano-sensation and immune pathways in age and pathology induced clinical challenges. This allowed us to analyse signalling pathways involved in compromised conditions to gain a more detailed understanding of the altered processes that need consideration in the development of new treatment approaches. Understanding the molecular mechanisms behind the conversion of positive stimuli into stressors under compromised conditions of bone healing may provide a blueprint for other organ systems where regeneration appears even more challenging or does not naturally occur.




Founded by the DFG (Project Number: 249509554)
Funding Period 2014-2022