Injectable hydrogels embedded with alginate microspheres for controlled delivery of bone morphogenetic protein-2

Abstract

Some delivery carriers with injectable characteristics were built using the thermosensitive chitosan/dextran-polylactide/glycerophosphate hydrogel and selected alginate microspheres for the controllable release of bone morphogenetic protein-2 (BMP-2). BMP-2 was first loaded into the microspheres with an average size of around 20 μm and the resulting microspheres were then embedded into the gel in order to achieve well-controlled BMP-2 release. The microsphere-embedded gels show their incipient gelation temperature at around 32 °C and pH at about 7.1. Some gels had their elastic modulus close to 1400 Pa and the ratio of elastic modulus to viscous modulus at around 34, revealing that they behaved like mechanically strong gels. Optimized microsphere-embedded gels were found to be able to administer the BMP-2 release without significant initial burst release in an approximately linear manner over a period of time longer than four weeks. The release rate and the released amount of BMP-2 from these gels could be regulated individually or cooperatively by the initial BMP-2 load and the dextran-polylactide content in the gels. Measurements of the BMP-2 induced alkaline phosphatase activity in C2C12 cells confirmed that C2C12 cells responded to BMP-2 in a dose-dependent way and the released BMP-2 from the microsphere-embedded gels well retained their bioactivity. In vivo assessment of some gels revealed that the released BMP-2 maintained its osteogenesis functions.

Hydrogels based on chitosan in tissue regeneration: How do they work? A mini review

“…Thus, the hydrogel could maintain the growth factor for a much longer time. Another case involved the encapsulation of the BMP‐2 microspheres into chitosan‐based hydrogels for its sustainable release . The two studies above confirmed the hydrogels, after being loaded with BMP‐2, showed significant abilities to induce the bone regeneration in vivo .…”

PCL microsphere/PEG‐based composite hydrogels for sustained release of methadone hydrochloride

“…Therefore, these carriers can be incorporated in the hydrogel to avoid a burst release of bioactive molecules from hydrogel because the hydrogel provide an extra diffusion barrier for drug release which increases the drug release period. There are many research based on the utilization of composite systems (microparticle embedded hydrogels) for control the drug or growth factor release . Delie and coworkers developed an easily applicable drug delivery system for the prevention of intimal hyperplasia, through a single administration of a cross‐linked hyaluronic acid hydrogel/poly‐lactic‐co‐glycolic acid (PLGA) microparticle formulation loaded with atorvastatin.…”

Chitosan-Based Nanofibrous Membrane Unit with Gradient Compositional and Structural Features for Mimicking Calcified Layer in Osteochondral Matrix

“…Similarly, type-I collagen content was also quantified using a collagen type I ELISA kit (rabbit) (US Biological, Salem, MA, USA). Alkaline phosphatase (ALP) activity was assessed while using an ALP assay kit (Abcam, Cambridge, MA, USA), and the ALP activity was normalized to the total protein content [45]. These quantitative measurements were performed following the protocols and instructions provided by manufactures.…”