Abstract
Previous studies performed using polysaccharide-based matrices supplemented with hydroxyapatite (HA) particles showed their ability to form in subcutaneous and intramuscular sites a mineralized and osteoid tissue. Our objectives are to optimize the HA content in the matrix and to test the combination of HA with strontium (Sr-HA) to increase the matrix bioactivity. First, non-doped Sr-HA powders were combined to the matrix at three different ratios and were implanted subcutaneously for 2 and 4 weeks. Interestingly, matrices showed radiolucent properties before implantation. Quantitative analysis of micro-CT data evidenced a significant increase of mineralized tissue formed ectopically with time of implantation and allowed us to select the best ratio of HA to polysaccharides of 30% (w/w). Then, two Sr-substitution of 8% and 50% were incorporated in the HA powders (8Sr-HA and 50Sr-HA). Both Sr-HA were chemically characterized and dispersed in matrices. In vitro studies performed with human mesenchymal stem cells (MSCs) demonstrated the absence of cytotoxicity of the Sr-doped matrices whatever the amount of incorporated Sr. They also supported osteoblastic differentiation and activated the expression of one late osteoblastic marker involved in the mineralization process i.e. osteopontin. In vivo, subcutaneous implantation of these Sr-doped matrices induced osteoid tissue and blood vessels formation.
Highlights
For patients encountering a surgical bone reconstruction, new developments in orthopaedic and cranio-maxillofacial surgery are expected, especially for non-union fractures, large bone defects, bone physiopathologies and bone reconstruction following tumor resection [1]
Tissue-engineered constructs are labor intensive to produce with low throughput, and these advanced cell therapies are associated with stringent regulatory hurdles
While the use of Bone Morphogenic Proteins (BMPs) has been approved for specific bone regeneration applications, their use is contraindicated in an oncological context, due to concerns that this anabolic growth factor may contribute to tumor cell proliferation [7]
Summary
For patients encountering a surgical bone reconstruction, new developments in orthopaedic and cranio-maxillofacial surgery are expected, especially for non-union fractures, large bone defects, bone physiopathologies and bone reconstruction following tumor resection [1]. In such clinical context, the reconstruction of large volume defects remains challenging because of a lack of vascularization of the newly formed tissue. When considering an oncological context for bone reconstruction, autologous undifferentiated cells with capacity for self-renewal have a potential for tumor formation. The development of cell-free and growth factor-free approaches for the replacement of diseased or damaged bone tissue is expected for such specific clinical needs
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