Factors influencing the drug release from calcium phosphate cements.

Silk fibroin provides a new option for controlled release systems as a result of its excellent biodegradability, biocompatibility, and mechanical properties. As the core material, silk fibroin can be designed and widely used in drug/gene delivery, regenerative medicine, and other biomedical fields. This review focuses on the preparation methods, loading molecules, and applications of silk fibroin-based controlled release systems including microspheres, microcapsules, films, microparticles, microneedles, liposomes, and hydrogels. These systems provide numerous advantages such as high encapsulation efficiency, avoiding loss of bioactivity and maintaining desirable range without peaks and valleys in comparison to the traditional administration approaches. Microsc. Res. Tech. 80:312-320, 2017. © 2015 Wiley Periodicals, Inc.

Preparation of silk fibroin carriers for controlled release.

Factors influencing the drug release from calcium phosphate cements

Bone morphogenetic protein 2 has a major role in promoting bone regeneration in tissue engineering scaffolds. Growth factor release rate is a remaining crucial problem in these systems. The aim of this study was to fabricate and characterize a novel calcium phosphate/polyphosphazenes porous scaffold for the sustained release of bone morphogenetic protein 2 in bone tissue engineering. Polyphosphazenes were substituted with 2-dimethylaminoethanol and evaluated by GPC, NMR, and in vitro degradation. Calcium phosphate porous samples were prepared from hydroxyapatite nanoparticles and naphthalene using the sintering method at 1250 °C before being composited with poly(dimethylaminoethanol)phosphazenes containing chitosan microspheres loaded with bone morphogenetic protein 2. The characteristics and biodegradability of the product were evaluated by SEM, XRD, and in vitro degradation. Moreover, the release rate and mechanical properties of the scaffolds were investigated. The release behavior was found to be sustained since the scaffolds had been fabricated from polyphosphazenes with a low degradation rate. The release rates of the scaffolds were observed to increase with increasing chitosan microspheres content from 10 to 30%. The bioactivity of the scaffolds depended on the release rate of growth factor while bone morphogenetic protein 2 was able to induce an osteoblast proliferation. The results of cell adhesion and cell viability tests showed that scaffolds displayed a non-toxic behavior and western blot analyses confirmed that the scaffolds loaded with growth factor increased the osteogenic differentiation potential of cells when compared with scaffolds alone. These results demonstrate that these scaffolds can be successfully utilized in bone tissue engineering.

/pdf/fabrication-and-characterization-of-polyphosphazene-calcium-5cetx1ajeo.pdf

Fabrication and Characterization of Polyphosphazene/Calcium Phosphate Scaffolds Containing Chitosan Microspheres for Sustained Release of Bone Morphogenetic Protein 2 in Bone Tissue Engineering

As the population ages, spinal degeneration seriously affects quality of life in middle-aged and elderly patients, and prevention and treatment remain challenging for clinical surgeons. In recent years, biomaterials-based injectable therapeutics have attracted much attention for spinal degeneration treatment due to their minimally invasive features and ability to perform precise repair of irregular defects. However, the precise design and functional control of bioactive injectable biomaterials for efficient spinal degeneration treatment remains a challenge. Although many injectable biomaterials have been reported for the treatment of spinal degeneration, there are few reviews on the advances and effects of injectable biomaterials for spinal degeneration treatment. This work reviews the current status of the design and fabrication of injectable biomaterials, including hydrogels, bone cements and scaffolds, microspheres and nanomaterials, and the current progress in applications for treating spinal degeneration. Additionally, registered clinical trials were also summarized and key challenges and clinical translational prospects for injectable materials for the treatment of spinal degenerative diseases are discussed. 

https://doi.org/10.1016/j.mtbio.2022.100336

Precision medicine strategies for spinal degenerative diseases: Injectable biomaterials with in situ repair and regeneration

To search for new bioactive materials which can be used as the substitute of bone repairing and drug carriers, Sema3A-loaded chitosan microspheres (SLCM) and silk fibroin (SF) were mixed with calcium sulfate cement (CSC). SEM, particle size analysis and swelling rate determination were performed to study properties of the microspheres. The drug loading, encapsulation efficiency and drug release rate were determined by ELISA. Microspheres with different SLCM weight contents (0.5%, 1% and 5%) were prepared to determine which one has the strongest mechanical properties and the appropriate setting time. It was revealed that CSC/SF/0.5SLCM has satisfactory mechanical properties, and its in vitro biocompatibility was assessed by MTS. Chitosan microspheres (5–18 μm) were globular, the surface was smooth, and the swelling rate is (77.02 ± 5.57)%. With this formula, the setting time was increased with the addition of SLCM in CSC/SF, and the cumulative drug release rate is 44.62% in 28 d. XRD results demonstrate that the main component is calcium sulfate. Also it was found that CSC/SF/0.5SLCM supports the growth of MC3T3 cells. Thus the preparation of CSC/SF/0.5SLCM was reliable, and the products had good structures, physical properties and biocompatibility, appearing to be a promising bone substitute material.

Preparation and properties of calcium sulfate bone cement incorporated with silk fibroin and Sema3A-loaded chitosan microspheres

The reinforcement of calcium phosphate materials with silk fibroin (SF) has been one of the strategies to overcome the brittleness. However, the lack of osteoinductivity may still restrict their further use. This study aimed to investigate the biocompatibility and osteogenesis capacity of a novel Semaphorin 3A-loaded chitosan microspheres/SF/α-tricalcium phosphate composite (Sema3A CMs/SF/α-TCP) in vitro. Sema3A was first incorporated into CMs, and the Sema3A CMs/SF/α-TCP composite was then prepared. The morphology of the CMs was observed using SEM. The in vitro release kinetics, cytotoxicity, and cell compatibility were evaluated, and the real-time quantitative polymerase chain reaction (RT-qPCR) and activity of alkaline phosphatase (ALP) were used to evaluate the osteogenesis capacity of the composite. The in vitro release of Sema3A from the Sema3A CMs/SF/α-TCP composite showed a temporally controlled manner. The extract of the Sema3A CMs/SF/α-TCP composite presented no obvious side effect on the MC3T3-E1 cell proliferation, nor promote cell proliferation. The MC3T3-E1 cells were well-spread and presented an elongated shape on the Sema3A CMs/SF/α-TCP composite surface; the ALP activity and the osteogenic-related gene expression were higher than those seeded on the surface of the CMs/SF/α-TCP and SF/α-TCP composites. In conclusion, Sema3A CMs/SF/α-TCP has excellent biocompatibility and contributes to the osteoblastic differentiation of MC3T3-E1 cells.

Sustained release of Semaphorin 3A from α-tricalcium phosphate based cement composite contributes to osteoblastic differentiation of MC3T3-E1 cells

The invention discloses a chitosan microsphere composite fibroin based calcium sulfate cement and a preparation method thereof. The injectable composite cement disclosed by the invention is prepared from mixed powder composed of chitosan microspheres and calcium sulfate and a fibroin solution in a solid-to-liquid ratio g/ml of 1:0.45. In the mixed powder, the content of the chitosan microspheres is 0.1%w/w-1%w/w, and the content of the calcium sulfate is 99%w/w-99.9%w/w. The method includes: firstly preparing the chitosan microspheres by an emulsification-chemical crosslinking technique, extracting fibroin fiber from silkworm silk to further prepare the fibroin solution, then mixing the chitosan microspheres with calcium sulfate powder, and then mixing the mixed powder with the fibroin solution according to certain solid-to-liquid ratio. The cement composite material provided by the invention can be injected to bone defect parts through percutaneous minimal invasion to repair bone defects, and also can be degraded and absorbed in vivo, thus being applied as a drug slow delivery system to release drugs or growth factors so as to act on filling positions for a long time.

Chitosan microsphere composite fibroin based calcium sulfate cement and preparation method thereof

Biodegradable GdPO4·H2O/PLGA microcarriers for stem cell delivery and non-invasive MRI translocation tracing

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Preparation and properties of calcium sulfate bone cement incorporated with silk fibroin and Sema3A-loaded chitosan microspheres

Sustained release of Semaphorin 3A from α-tricalcium phosphate based cement composite contributes to osteoblastic differentiation of MC3T3-E1 cells

Chitosan microsphere composite fibroin based calcium sulfate cement and preparation method thereof

Biodegradable GdPO4·H2O/PLGA microcarriers for stem cell delivery and non-invasive MRI translocation tracing