This paper presents a review of the rationale for the in vitro mineralization process, preparation methods, and clinical applications of mineralized collagen. The rationale for natural mineralized collagen and the related mineralization process has been investigated for decades. Based on the understanding of natural mineralized collagen and its formation process, many attempts have been made to prepare biomimetic materials that resemble natural mineralized collagen in both composition and structure. To date, a number of bone substitute materials have been developed based on the principles of mineralized collagen, and some of them have been commercialized and approved by regulatory agencies. The clinical outcomes of mineralized collagen are of significance to advance the evaluation and improvement of related medical device products. Some representative clinical cases have been reported, and there are more clinical applications and long-term follow-ups that currently being performed by many research groups.

In this study, human mesenchymal stem cells (hMSCs) were cultured on the hydroxyapatite (HA) and mineralized collagen (MC), and their proliferation, adhesion and differentiation, especially the molecular mechanisms on gene level were investigated. Proliferation and morphological responses of hMSCs and their osteogenic differentiation were detected by quantitative detection of alkaline phosphatase. Gene expression profilings were examined by microarrays and the gene expressions data were studied through gene ontology terms and pathway analyses. The results showed that MC promoted cell proliferation and osteogenic differentiation of hMSCs. Microarray analysis showed that MC was conducive to express osteogenesis-related genes, such as BMP-2, COL1A1, CTSK, and stimulate osteogenic differentiation, like osteoblast differentiation pathway and skeletal system development pathway.

Polymethyl methacrylate (PMMA) bone cement is a commonly used bone adhesive and filling material in percutaneous vertebroplasty and percutaneous kyphoplasty surgeries. However, PMMA bone cements have been reported to cause some severe complications, such as secondary fracture of adjacent vertebral bodies, and loosening or even dislodgement of the set PMMA bone cement, due to the over-high elastic modulus and poor osteointegration ability of the PMMA. In this study, mineralized collagen (MC) with biomimetic microstructure and good osteogenic activity was added to commercially available PMMA bone cement products, in order to improve both the mechanical properties and the cytocompatibility. As the compressive strength of the modified bone cements remained well, the compressive elastic modulus could be significantly down-regulated by the MC, so as to reduce the pressure on the adjacent vertebral bodies. Meanwhile, the adhesion and proliferation of pre-osteoblasts on the modified bone cements were improved compared with cells on those unmodified, such result is beneficial for a good osteointegration formation between the bone cement and the host bone tissue in clinical applications. Moreover, the modification of the PMMA bone cements by adding MC did not significantly influence the injectability and processing times of the cement.

To investigate the clinical results of treating Kummell’s Disease by using mineralized collagen modified polymethyl methacrylate bone cement, 23 cases (23 vertebras) who sustained Kummell’s Disease treated with mineralized collagen modified polymethyl methacrylate bone cement from July 2017 to February 2019 were reviewed retrospectively. The visual analogue scale, vertebral body height, Cobb angle, CT values pre-operation and post-operation as well as incidence of complications were observed. All the patients were successfully followed up with an average period of 11.3 months (ranging from 6 to 12 months). The patients could ambulate on the second day after the operation. The visual analogue scale scores significantly decreased from two days after the operation to the last follow-up compared with that before the operation (p < 0.05); the average vertebral height and local Cobb angle had significant recovery (p < 0.05); the CT value of the treated vertebra significantly increased compared with that before the operation (p < 0.05). Bone cement leakage occurred in one case, anterior edge leakage occurred in one case, and no clinical symptoms caused by bone cement leakage occurred. No re-fracture of the treated vertebral body or adjacent vertebral bodies were observed in the follow-ups. With good osteogenic activity and degradable absorption characteristics, mineralized collagen was compounded with the existing polymethyl methacrylate bone cement to reduce its strength in the vertebral body and enhance biocompatibility, the incidence of adjacent vertebral fractures and re-fractures within the injured vertebrae is significantly reduced, and good clinical results are obtained, which is worthy of popularization.