RMD/
Articles/
2504000254
  • Open Access
  • Review
Insights into Bioengineering Approaches for Aging Bone Regeneration: Strategies to Target Osteoimmunosenescence
  • Lan Xiao 1, 2, †,   
  • Wendong Gao 1, 2, †,   
  • Jinfu Wu 3,   
  • Itsasne Erezuma 4,   
  • Alireza Dolatshahi-Pirouz 5,   
  • Joana Silva-Correia 6, 7,   
  • Yinghong Zhou 2, 8,   
  • Antonia Rujia Sun 2, 9,   
  • Indira Prasadam 2, 9,   
  • Ross Crawford 2, 9,   
  • Joaquim Miguel Oliveira 6, 7,   
  • Gorka Orive 5, 10, 11, 12, 13,   
  • Chengtie Wu 3,   
  • Yin Xiao 1, 2, *

Received: 22 Oct 2024 | Revised: 08 Jan 2025 | Accepted: 15 Jan 2025 | Published: 22 Jan 2025

Abstract

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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DOI
10.53941/rmd.2025.100001
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Volume 2, Issue 1
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Xiao, L.; Gao, W.; Wu, J.; Erezuma, I.; Dolatshahi-Pirouz, A.; Silva-Correia, J.; Zhou, Y.; Sun, A. R.; Prasadam, I.; Crawford, R.; Oliveira, J. M.; Orive, G.; Wu, C.; Xiao, Y. Insights into Bioengineering Approaches for Aging Bone Regeneration: Strategies to Target Osteoimmunosenescence. Regenerative Medicine and Dentistry 2025, 2 (1), 1. https://doi.org/10.53941/rmd.2025.100001.
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