Chitosan-Based Hydrogels Embedded with Hyaluronic Acid Complex Nanoparticles for Controlled Delivery of Bone Morphogenetic Protein-2

Abstract

Chitosan(CH)-poly(dioxanone) (CH-PDO) copolymers containing varied amounts of PDO and having free amino groups at their CH backbone were synthesized using a group protection method. The selected CH-PDO with soluble characteristics in aqueous media was used together with hyaluronic acid (HA) to prepare HA/CH-PDO polyelectrolyte complex nanoparticles (NPs) via an ionotropic gelation technique, and such a type of HA/CH-PDO NPs was employed as a carrier for delivering bone morphogenetic protein-2 (BMP-2). The optimal BMP-2-encapsulated HA/CH-PDO NPs with high encapsulation efficiency were embedded into CH/glycerophosphate composite solutions to form different hydrogels in order to achieve long-term BMP-2 release. The formulated gels were found to be injectable at room temperature and had its thermosensitive phase transition near physiological temperature and pH. They also showed abilities to administer the release of BMP-2 in approximately linear manners for a few weeks while effectively preserving the bioactivity of the encapsulated BMP-2. In view of their fully biocompatible and biodegradable components, the presently developed gel systems have promising potential for translation to the clinic use in bone repair and regeneration where the sustained and controlled stimuli from active signaling molecules and the stable biomechanical framework for housing the recruited cells are often concurrently needed.

Magnesium hydroxide-incorporated PLGA composite attenuates inflammation and promotes BMP2-induced bone formation in spinal fusion

“… 38 As mentioned previously, many approaches are available to overcome the disadvantages of BMP2 and improve both its safety and therapeutic efficacy by utilizing different carrier systems. 5 , 10 – 16 , 38 The release profile of BMP2 from PLGA/BMP2 and PLGA/MH/BMP2 exhibited an initial burst release followed by slow release for up to 8 weeks ( Figure 3(b) and ( c )). Interestingly, the PLGA/MH/BMP2 film indicated a more significant release of BMP2 when compared to PLGA/BMP2 film.…”

“…The carriers used for delivery are made of metals, ceramics, polymers, and composites. 5,[10][11][12][13][14][15][16][17][18][19] Poly(lactic-co-glycolic acid) (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. 16,18,20 Many PLGA delivery systems for BMP2 have shown promise for bone repair.…”

“…Many carriers and delivery systems comprised of different materials have been investigated to maintain the controlled release and improve the safety and therapeutic efficacy of BMP2. 5 , 10 – 16 The delivery systems come in the form of hydrogels, microspheres, nanoparticles, and fibers. The carriers used for delivery are made of metals, ceramics, polymers, and composites.…”

Martini Coarse-Grained Model of Hyaluronic Acid for the Structural Change of Its Gel in the Presence of Monovalent and Divalent Salts

“…We believe these developed procedures could serve as a useful reference for further coarse-grained modeling of other polyelectrolytes in order to enable mesoscale simulations with large molecules. Our model developed here can be used in conjunction with other Martini models, and can be further expanded to model various HA polymers and their modified polyelectrolytes, for example, the process of physical crosslinking of HA in the presence of phospholipids (HA–PL complex) in the lubrication of articular cartilage [ 47 , 48 ], self-assembly of polymeric nanoparticles in drug delivery [ 49 , 50 ], novel HA-based biocompatible and biodegradable hydrogels for in vitro cell culture [ 2 , 51 ], cartilage tissue engineering [ 3 ], and the charge-based purification of protein drugs [ 4 ].…”

Controlled Delivery of Insulin-like Growth Factor-1 from Bioactive Glass-Incorporated Alginate-Poloxamer/Silk Fibroin Hydrogels

“…It is generally realized that directly encapsulating growth factors into hydrogels would result in their burst release because hydrogels commonly have rather porous structures with high water content [ 7 , 20 ]. It has been suggested that release kinetics of growth factors delivered by a hydrogel system could be mediated to varied degrees by encapsulating the growth factor into certain microcarriers such as microspheres (MPs) and nanoparticles (NPs) first, and then, embedding the factor-loaded microcarrier into the hydrogel system [ 20 , 21 , 22 ].…”