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Biogenic collagen membranes (BCM) have been widely used in guided bone regeneration (GBR) owing to their biodegradability during tissue integration. However, their relatively high degradation rate and lack of pro-osteogenic properties limit their clinical outcomes. It is of great importance to endow BCM with tailored degradation as well as pro-osteogenic properties. In this study, a fluoride-modified polymer-induced liquid precursor (PILP) based biomineralization strategy was used to convert the collagen membrane from an organic phase to an apatite-based inorganic phase, thus achieving enhanced anti-degradation performance as well as osteogenesis. As a result, three phases of collagen membranes were prepared. The original BCM in the organic phase induced the mildest inflammatory response and was mostly degraded after 4 weeks. The organic-inorganic mixture phase of the collagen membrane evoked a prominent inflammatory response owing to the fluoride-containing amorphous calcium phosphate (F-ACP) nanoparticles, resulting in active angiogenesis and fibrous encapsulation, whereas the inorganic phase induced a mild inflammatory response and degraded the least owing to the transition of F-ACP particles into calcium phosphate with high crystallinity. Effective control of ACP is key to building novel apatite-based barrier membranes. The current results may pave the way for the development of advanced apatite-based membranes with enhanced barrier performances. [ABSTRACT FROM AUTHOR]

BACKGROUND: Biological hydroxyapatite (BHA)-based bone grafting materials have been widely used for bone regeneration in implant surgery. Much effort has been made in the improvement of their osteogenic property as it remains unsatisfactory for clinical use. Osteoimmunomodulation plays a significant role in bone regeneration, which is highly related to active inorganic ions. Therefore, attempts have been made to obtain osteoimmunomodulatory BHA-based bone grafting materials with optimized osteogenic property by ion doping. OBJECTIVE: To summarize and discuss the active inorganic ions doped into BHA and their effects on BHA-based bone grafting materials. METHOD: A literature search was performed in databases including Google Scholar, Web of Science and PubMed, with the elementary keywords of "ion doped" and "biological hydroxyapatite", as well as several supplementary keywords. All document types were included in this search. The searching period and language were not limited and kept updated to 2022. RESULTS: A total of 32 articles were finally included, of which 32 discussed the physiochemical properties of BHA-based biomaterials, while 12 investigated their biological features in vitro, and only three examined their biological performance in vivo. Various ions were doped into BHA, including fluoride, zinc, magnesium and lithium. Such ions improved the biological performance of BHA-based biomaterials, which was attributed to their osteoimmunomodulatory effect. CONCLUSION: The doping of active inorganic ions is a reliable strategy to endow BHA-based biomaterials with osteoimmunomodulatory property and promote bone regeneration. Further studies are still in need to explore more ions and their effects in the crosstalk between the skeletal and immune systems. [ABSTRACT FROM AUTHOR]