Microbial Stimulation for Bone Regeneration

Bone has an inherent ability to heal itself; however, in cases of large defects caused by trauma, disease, or surgical resection, this natural repair is insufficient. Autografts remain the clinical gold standard but are limited by donor site morbidity, restricted availability, and additional surgical burden. Consequently, calcium phosphate (CaP) biomaterials have been widely explored as substitutes. Traditionally, research has focused on their structural and osteoconductive properties, but advances in osteoimmunology highlight that immune responses plays an important role in the success of bone healing. This emerging field of osteoimmunomodulation proposes that biomaterials should be designed to actively influence the immune environment.

This thesis explores the use of microbial components as immune-modulatory cues to enhance bone regeneration. Pathogen-associated molecular patterns (PAMPs), recognized by innate immune receptors, were incorporated into CaP-based substitutes. The study assessed the effects of selected microbial components on bone regeneration through a combination of in vitro cell culture assays and in vivo animal models. Special attention was given to the role of innate immune memory in shaping osteoblast and osteoclast activity.

The findings demonstrate that microbial components exert divergent effects on bone healing. BCG and CpG ODN C induced favorable responses that promoted osteoblast differentiation and bone formation, whereas Poly(I:C) and LPS hindered bone formation. Moreover, macrophage training with BCG enhanced osteogenic potential and supported osteoclast function, while tolerization with LPS suppressed both osteoblast and osteoclast differentiation. These results establish that the type and regulation of immune activation are pivotal for determining whether bone regeneration succeeds or fails.

The research confirms that the immune system is not a passive participant but an active regulator of bone healing. A controlled, well-balanced inflammatory response can stimulate regeneration, whereas excessive or chronic immune activation impedes it. Importantly, the study highlights that innate immune memory, shaped by past microbial exposures, can influence patient-specific healing outcomes, offering opportunities for personalized approaches in regenerative medicine.