Controlled drug release for tissue engineering.

Bone defects caused by trauma or pathological events are major clinical and socioeconomic burdens. Thus, the efforts of regenerative medicine have been focused on the development of non-biodegradable materials resembling bone features. Consequently, the use of bioactive glass as a promising alternative to inert graft materials has been proposed. Bioactive glass is a synthetic silica-based material with excellent mechanical properties able to bond to the host bone tissue. Indeed, when immersed in physiological fluids, bioactive glass reacts, developing an apatite layer on the granule’s surface, playing a key role in the osteogenesis process. Moreover, the contact of bioactive glass with biological fluids results in the increase of osmotic pressure and pH due to the leaching of ions from granules’ surface, thus making the surrounding environment hostile to microbial growth. The bioactive glass antimicrobial activity is effective against a wide selection of aerobic and anaerobic bacteria, either in planktonic or sessile forms. Furthermore, bioglass is able to reduce pathogens’ biofilm production. For the aforementioned reasons, the use of bioactive glass might be a promising solution for the reconstruction of bone defects, as well as for the treatment and eradication of bone infections, characterized by bone necrosis and destruction of the bone structure.

Recent Evidence on Bioactive Glass Antimicrobial and Antibiofilm Activity: A Mini-Review.

A great deal of research is ongoing in the area of tissue engineering (TE) for bone regeneration. A possible improvement in restoring damaged tissues involves the loading of drugs such as proteins, genes, growth factors, antibiotics, and anti-inflammatory drugs into scaffolds for tissue regeneration. This mini-review is focused on the combination of the local delivery of antibiotic agents with bone regenerative therapy for the treatment of a severe bone infection such as osteomyelitis. The review includes a brief explanation of scaffolds for bone regeneration including scaffolds characteristics and types, a focus on severe bone infections (especially osteomyelitis and its treatment), and a literature review of local antibiotic delivery by the combination of scaffolds and drug-delivery systems. Some examples related to published studies on gentamicin sulfate-loaded drug-delivery systems combined with scaffolds are discussed, and future perspectives are highlighted.

https://www.mdpi.com/1424-8247/10/4/96/pdf

Biodegradable Scaffolds for Bone Regeneration Combined with Drug-Delivery Systems in Osteomyelitis Therapy.

Advances in dual functional antimicrobial and osteoinductive biomaterials for orthopaedic applications

An insight into functionalized calcium based inorganic nanomaterials in biomedicine: Trends and transitions.

The ability of silica calcium phosphate nanocomposite (SCPC75) for the controlled sequential delivery of vancomycin (Vanc) and rhBMP2 was evaluated. Fourier transform infrared spectroscopy analyses of the SCPC75 showed an increase in the bond energy of the PO4 (-3) due to the interactions with negatively charged moieties of Vanc. Furthermore, a decrease in the bond energy of the Si-O-Si functional groups was observed after rhBMP2 adsorption. In conjunction with the differences in bond site and bond energy at the ceramic/drug interface, significant differences in drug release kinetics and bioceramic dissolution rate were found. UV-vis spectrometry showed a burst release of Vanc in the first 8 h followed by a sustained release stage for up to 28 days. ELISA showed first-order release kinetics of rhBMP2 without burst release. The rhBMP2 release from SCPC75 was associated with a significantly lower rate of Ca and a higher rate of Si dissolutions when compared with Vanc release over identical time periods. Differences in the release kinetic profiles of Vanc and rhBMP2 from the SCPC75-Vanc/SCPC75-rhBMP2 scaffolds at 70/30, 50/50, or 20/80 ratios allowed for sequential drug release profiles that could be exploited to customize doses and release duration of each drug. The released rhBMP2 significantly upregulated MC3T3-E1 expression of collagen type I, osteopontin, and osteocalcin mRNA by 12.6-, 3.3-, and 2.4-fold, respectively. The released Vanc demonstrated bactericidal effects on Staphylococcus aureus in vitro. These results suggest the potential of SCPC75-Vanc-rhBMP2 scaffolds in the treatment of damaged and/or infected bone.

Tissue engineering scaffold for sequential release of vancomycin and rhBMP2 to treat bone infections

Hepatocellular carcinoma (HCC) is notoriously difficult to treat with systemic chemotherapy. The aim of this study was to evaluate a silica-calcium-phosphate nanocomposite (SCPC75) drug delivery system (DDS) as a means to localize cisplatin treatment within the tumor, while reducing systemic toxicity, in a rat model of HCC. The SCPC75 was prepared and loaded with cisplatin and Fourier transform infrared analyses demonstrated even drug distribution within the SCPC75. A rat model of subcutaneous HCC formation was established and animals treated by either systemic cisplatin injection (sCis) or with SCPC75-Cis hybrid placed adjacent (ADJ) to or within (IT) the tumor. Five days after implantation, 50-55% of the total cisplatin loaded had been released from the SCPC75-Cis hybrids resulting in an approximately 50% decrease in tumor volume compared with sCis treatment. sCis-treated animals exhibited severe side effects, including rapid weight loss and decreased liver and kidney function, effects not observed in SCPC75-Cis-treated animals. Analysis of cisplatin distribution demonstrated drug concentrations in the tumor were 21 and 1.5 times higher in IT and ADJ groups, respectively, compared with sCis-treated animals. These data demonstrate the SCPC75 DDS can provide an effective, localized treatment for HCC with significantly reduced toxicity when compared with systemic drug administration.

A silica-calcium-phosphate nanocomposite drug delivery system for the treatment of hepatocellular carcinoma: in vivo study.

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Tissue engineering scaffold for sequential release of vancomycin and rhBMP2 to treat bone infections

A silica-calcium-phosphate nanocomposite drug delivery system for the treatment of hepatocellular carcinoma: in vivo study.