Osteosarcoma (OS) is a highly malignant primary tumor frequently occurring in children and adolescents. The mainstay of therapy is neoadjuvant chemotherapy and surgical removal of the lesion yielding a 50–70% of 5-year survival rate. Unfortunately, chemotherapy is currently unable to induce complete tumor necrosis leaving residual tumor cells free to metastasize or recidivate, thus resulting in a 30% mortality. The major limitation in those patients is the development of multidrug resistance (MDR) and the low water solubility of drugs such as Paclitaxel (PTX) that is in fact not included in the majority of chemotherapy protocols for OS treatment. We thus hypothesized to prevent the emergence of MDR and obtain significant tumor reduction, by engineering innovative nanoparticles (NPs) able to vehiculate the PTX and induce a dual synergic action: the cytostatic effect of PTX and the cytotoxicity generated by reactive oxygen species produced from light triggered photoactivation (PDT) of Chlorin e6 photosensitizer. To further improve the efficacy and reduce the side effects of NPs systemic administration, Mesenchymal Stromal Cells (MSC) are used as a “Trojan horse” to deliver the NPs directly to tumor cells, taking advantage of MSC ability to selectively recognize and efficiently engraft in OS tumor stroma. HSA were conjugated with photosensitizer Ce6 and the functionalized protein was used to produce PTX loaded nanoparticles through desolvation technique and drug-induced protein self-assembly (PTX-Ce6@HSA NP). Human MSC lines, isolated from the Bone marrow (BM) of different donors, were then loaded with different dosages of nanoparticles and their ability to internalize and transport the NPs, migrate and induce cytotoxic ROS upon light treatment were tested in in vitro cultures. Preliminary results showed that MSC efficiently internalize PTX-Ce6@HSA NPs and the photosensitizer Ce6 remains active inside the cells for at least 3 days after loading. Electron microscopy performed onto loaded MSC showed that NPs internalization take places via clathrin mediated transport, whereas HPLC analysis demonstrated a release kinetics of PTX mediated by exocytosis. Finally, PTX-Ce6@HSA NPs loaded MSC co-cultured with the OS tumor cell line SaOS-2 showed a significant tumor cell growth reduction. So fare, advances in drug delivery have failed to produce specific tool to improve the overall survival of OS patients. However, given our preliminary In the future, our strategy could be intended as an innovative co-adjuvant approach for OS treatment to be performed right before surgery to eliminate residual tumors cells after tumor mass removal.
Demineralized bone matrix (DBM) is a natural, collagen-based, well-established osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM osteoinductivity. Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1–2 mm), medium (M, 0.5–1 mm), and small (S, < 0.5 mm). After demineralization, the three DBM samples were characterized by DTA analysis, XRD, ICP-OES, and FTIR. Data clearly showed a particle size-dependent alteration in collagen structure, with DBM-M being altered but not as much as DBM-S. The
The delay looks radiographically as a fracture callus not very evident or absent 6 months after osteosynthesis. Patients undergo a long period of immobilization and this fact causes the increase the social cost of the disease. The technique we suggest aims to the reduce the period of immobilization and as a consequence the management costs of the disease. Our technique includes the infiltration of the delay focus with platelet rich fibrin, bone marrow concentrated and demineralized bone matrix. Outpatients and radiographic checks were carried out 3, 6 and 12 months after surgery. The treatment was considered fail in case of absence of bone callus at 3 out of 4 corticals at the rx after 6 months from surgery.Introduction
Materials and methods
We retrospectively reviewed 101 consecutive patients
with 114 femoral tumours treated by massive bone allograft at our
institution between 1986 and 2005. There were 49 females and 52
males with a mean age of 20 years (4 to 74). At a median follow-up
of 9.3 years (2 to 19.8), 36 reconstructions (31.5%) had failed.
The allograft itself failed in 27 reconstructions (24%). Mechanical complications such as delayed union, fracture and
failure of fixation were studied. The most adverse factor on the
outcome was the use of intramedullary nails, followed by post-operative
chemotherapy, resection length >
17 cm and age >
18 years at the
time of intervention. The simultaneous use of a vascularised fibular
graft to protect the allograft from mechanical complications improved
the outcome, but the use of intramedullary cementing was not as
successful. In order to improve the strength of the reconstruction and to
advance the biology of host–graft integration, we suggest avoiding
the use of intramedullary nails and titanium plates, but instead
using stainless steel plates, as these gave better results. The
use of a supplementary vascularised fibular graft should be strongly
considered in adult patients with resection >
17 cm and in those
who require post-operative chemotherapy.