Evaluation of a Thiolated Chitosan Scaffold for Local Delivery of BMP-2 for Osteogenic Differentiation and Ectopic Bone Formation

Abstract

Thiolated chitosan (Thio-CS) is a well-established pharmaceutical excipient for drug delivery. However, its use as a scaffold for bone formation has not been investigated. The aim of this study was to evaluate the potential of Thio-CS in bone morphogenetic protein-2 (BMP-2) delivery and bone formation. In vitro study showed that BMP-2 interacted with the Thio-CS and did not affect the swelling behavior. The release kinetics of BMP-2 from the Thio-CS was slightly delayed (70%) within 7 days compared with that from collagen gel (Col-gel, 85%), which is widely used in BMP-2 delivery. The BMP-2 released from Thio-CS increased osteoblastic cell differentiation but did not show any cytotoxicity until 21 days. Analysis of the in vivo ectopic bone formation at 4 weeks of posttransplantation showed that use of Thio-CS for BMP-2 delivery induced more bone formation to a greater extent (1.8 fold) than that of Col-gel. However, bone mineral density in both bones was equivalent, regardless of Thio-CS or Col-gel carrier. Taken together, Thio-CS system might be useful for delivering osteogenic protein BMP-2 and present a promising bone regeneration strategy.

Injectable porous nano-hydroxyapatite/chitosan/tripolyphosphate scaffolds with improved compressive strength for bone regeneration

“…To obtain higher mechanically rigid scaffolds, chitosan can be incorporated with synthetic and natural polymers, ceramics and composite materials [20-23]. Bioceramics such as hydroxyapatite (HA) and its powdered subgroup β-tricalcium phosphate have proven to improve the biocompatibility, mimic the inorganic component of the bone and improving the mechanical strength of scaffolds [24-26].…”

A caninein vitromodel for evaluation of marrow‐derived mesenchymal stromal cell‐based bone scaffolds

“…By way of further comparison, addition of 0.1 mg/ mL of BMP2 (1000 times the current dose) to thiolated chitosan scaffolds promoted a fourfold increase in calcium deposition after 21 days of culture in osteogenic media. 89 In contrast to matrix mineralization, the addition of BMP2 to PEG-PDMS networks did not promote a significant increase in the osteogenic ECM protein Col-1 relative to PEG-PDMS scaffolds, despite the marked increase in Col-1 noted with the incorporation of BMP2 alone. In addition, the addition of PDMS to pure PEG scaffolds appeared to reduce Col-1 deposition relative to PEG only controls.…”

“…We report a 1.9-fold increase with 100 ng/mL BMP2 addition to PEG-PDMS constructs cultured for 21 days in the absence of osteogenic supplements. By way of further comparison, addition of 0.1 mg/ml of BMP2 (1000 times the current dose) to thiolated chitosan scaffolds promoted a 4-fold increase in calcium deposition after 21 days of culture in osteogenic media 90 .…”

Current and future options of regeneration methods and reconstructive surgery of the facial skeleton

“…After transferrence of the plasmid DNA into the cell nucleus, transcription begins and the synthesis of the GF can be initiated (76). Natural polymers such as chitosan used as GAM have the advantage of a higher infiltration of the surrounding tissue cells, as do synthetic polymers (77,78). Recently, the limited transfection rates of chitosan have been discussed.…”