Osteoporosis is a common bone disease causing 9 million new fractures each year. In addition to causing severe chronic pain to millions of people around the world, it also poses additional challenges to established medical procedures, especially bone and dental implants, for two main reasons.
1) First, osteoporosis systemically reduces bone mass, reduces the number and activity of osteoprogenitor cells, increases the risk of fracture, and prolongs the healing process.
2) Secondly, osteoporosis is accompanied by persistent inflammation, which destroys the local bone-immune balance, further destroys the integration of bone implants and hinders wound healing.
Therefore, although modern implants achieve high success rates under normal conditions, they still struggle to establish an ideal bone-implant structural connection and encounter more failures under osteoporotic conditions.
New approaches to improve bone-implant integration should address the fundamental dilemma of inflammation: appropriate inflammation is needed early on but should be suppressed later for better healing, especially under osteoporosis. However, precise switching of inflammation around implants in the body remains elusive.
Introduction to results:
In order to meet this challenge, Wang Chunming of the University of Macau, Dong Lei of Nanjing University and others designed a "burning bridges" coating material. The coating material contains glycans (acBSP) that can activate macrophages and covalently cross-linked Bisphosphonate (ALN) removes macrophages and coats titanium implants to improve bone implant integration in osteoporosis. The results were published in the journal Advanced Functional Materials.
Function of respective ingredients
Glycan acBSP has the unique activity of stimulating macrophage production of osteogenic (e.g., oncostatin M, OSM) and pro-angiogenic (e.g., vascular endothelial growth factor, VEGF) cytokines, which is ideal in this application of.
Bisphosphonates are the "triggers" of the "on-off" switch and have three effects:
i) Innovatively act as a cross-linker to bridge glycans and Ti surfaces;
ii) reacts to alkaline phosphatase (ALP), an early osteogenic marker with specific enzymatic activity that hydrolyzes phosphate bonds;
iii) Inducing macrophage apoptosis;
Burning bridges strategy
After implantation, acBSP stimulates macrophages to a desired pro-inflammatory and regenerative phenotype. Meanwhile, acBSP is covalently bonded to the Ti surface to cover ALN. As healing proceeds, osteoblast factors secreted by macrophages induce osteoblast differentiation and produce ALP, which rises to a certain level to begin to cleave the phosphate bond between ALN and Ti, thereby releasing ALN from the Ti surface. -acBSP complex. The hydrophobicity of the acetyl group and the hydrophilicity of the glucomannan sugar chain (and ALN) allow the complex to form nanoassemblies that can be further internalized by macrophages via carbohydrate receptors and trigger their apoptosis, leading to inflammation. subside.
To put it simply, after implantation, glycans instruct host macrophages to release bone-promoting cytokines ("turn on") and promote bone cell differentiation. Later, increasingly mature bone cells secrete alkaline phosphatase to cleave the glycan-bisphosphonate complex from the implant, thereby selectively killing pro-inflammatory macrophages that have completed their contribution (" closure”), thus promoting recovery in a “burning bridges” manner.
no other means needed
By physiologically switching inflammation "on-off", the coating enhanced bone implant integration and improved the immune microenvironment around the implant in osteoporotic rats. No other osteogenic cytokines, transgenic approaches, surgical procedures, or immunosuppressive drugs were used throughout and after implantation to achieve this therapeutic effect. No adverse effects caused by the coating were observed in animals. In vivo testing in an osteoporosis rat model showed that the coating significantly enhanced bone-implant integration (up to 88.4% contact rate) by regulating local inflammatory foci.
summary:
In summary, this article designed an intelligent, bioactive, and physiologically responsive glycan coating for Ti implants to improve their therapeutic performance under osteoporosis pathological conditions. Unlike traditional approaches that suppress host immune responses or inflammation, this coating system demonstrates "on-off" modulation of the healing response of local inflammation at the implant site, bidirectionally harnessing the ability of the host immune response to promote bone implant integration.
This immunomodulatory glycan coating represents an effective, safe, and universally applicable strategy for designing new biomaterial surfaces for a wide range of regenerative applications, particularly those serving patients with diseases such as osteoporosis. .
