The global accumulation of ageing population is a serious problem
causing significant health and social burdens. Especially, aging results in reduced
bone regeneration potential and increased risk of morbidities and mortality, which
calls the urgent need for advanced therapeutic approaches to improve bone
regeneration in the aged patients. The aging associated poor bone regeneration
capacity can be attributed to the low-grade, sterile chronic inflammation termed
“inflammaging”, which result in detrimental environment for bone healing. The
pathogenesis of inflammaging is mainly due to the senescence of immune cells. The
senescent immune cells, especially senescent macrophages play a major role in
inflammaging via an inflammatory secretome (senescence-associated secretory
phenotype/SASP) which is due to ROS accumulation associated mitochondrial
dysfunction, energy metabolism change, decline in oxidized nicotinamide adenine
dinucleotide (NAD+) level and insufficient autophagy. In addition, the SASP can
turn the local young cells into senescent cells, a paracrine senescence effect to
facilitate senescent cell accumulation and inflammation, which can also be
attributed to the insufficient clearance of senescent cells due to phagocytosis
deficiency in senescent immune cells. Therefore, in aging bone environment, the
interplay between immune and skeletal cells, termed “osteoimmunosenescence” in
this review, not only generates a long-term chronical inflammatory environment to
reduce osteogenesis, but also induces senescence in young skeletal progenitor cells
to dampen their osteogenic differentiation potential, suggesting
osteoimmunosenescence should be considered as a key modulatory target for bone
regeneration biomaterials design for the aged patients. In this review, the
pathogenesis of inflammaging and the potential impact of osteoimmunosenescence
on bone regeneration have been discussed. In addition, to target
osteoimmunosenescence, two potential strategies are considered, one is advanced
immunomodulation to correct the inflammaging environment, the other is to target
immunosenescence, and the current and potential material approaches regarding
these two are summarized in this review. Furthermore, it proposes potential
strategies to design osteoimmunosenescence-modulating materials by targeting the
molecular intersection between senescence and inflammation and by flexibly
correct the local environment and environmental responsively induce osteogenesis.
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