Cyclic acetal hydrogel system for bone marrow stromal cell encapsulation and osteodifferentiation

Abstract

Many systems have been proposed for the encapsulation of bone marrow stromal cells (BMSCs) within degradable hydrogels. Here, we use a novel cyclic acetal-based biomaterial formed from 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). A cyclic acetal-based hydrogel may be preferred as cyclic acetals hydrolytically degraded into diols and carbonyls as primary degradation products, which may not affect local acidity, unlike other widely investigated polymers. The EHD monomer and PEGDA polymer may be fabricated into a EH-PEG hydrogel by radical polymerization initiated by the ammonium persulfate (APS) and N,N,N',N'-tetramethylethylenediamine (TEMED) system. The objective of this work is to determine whether the components utilized in the fabrication of EH-PEG hydrogels as well as the EH-PEG hydrogels permit BMSC viability, metabolic activity, and osteodifferentiation. Cell viability and metabolic activity were assessed after 30 min, 1 h, and 3 h of exposure to pertinent concentrations of the initiator system (10-20 mM). Osteodifferentiation was assessed by alkaline phosphatase and osteocalcin expression after a short exposure to the initiator system to simulate the encapsulation process. Lastly, cell viability was assessed immediately after encapsulation and after 7 days of culture within the EH-PEG hydrogels. Results indicate that the metabolic activity and viability of BMSCs are minimally affected, and that osteodifferentiation is not significantly affected by the APS-TEMED initiator system. Also, encapsulated BMSCs maintained viability within EH-PEG hydrogels for 7 days. This work demonstrates that the EH-PEG hydrogel is a viable option for the encapsulation and osteodifferentiation of BMSCs.

Biodegradable polymers for dental tissue engineering and regeneration

“…PA microparticles and nanoparticles are used as delivery systems in the treatment of acute inflammatory diseases [218], ischemic heart diseases [219], and cancer and vaccines [220]. For most implant applications, cyclic polyacetal homopolymers and those copolymerized with poly(ethylene glycol) (PEG) diacrylate have shown preliminary promise as osteogenic biomaterials for bone tissue engineering [221]. In dentistry, the use of PA is widely diffused in restoration.…”

Recent Developments in Cyclic Acetal Biomaterials for Tissue Engineering Applications

“…The cyclic acetal unit hydrolytically degrades, forming products terminated with diol and carbonyl end groups. Recent studies have described the development of CAB's for tissue engineering applications (22,(57)(58)(59).…”

“…In order to investigate the utility of EH-PEG hydrogels as cell carriers, a series of studies were also undertaken to examine the viability and function of embedded osteoprogenitor cells (57). Specifically, this work examined (1) the effect of radical initiators on viability and metabolic activity of osteoprogenitor cells in monolayer, (2) the ability of the osteoprogenitor cells to differentiate after initiator exposure, and (3) the viability of osteoprogenitor cells embedded in the EH-PEG hydrogels.…”

Porous EH and EH-PEG Scaffolds as Gene Delivery Vehicles to Skeletal Muscle

“…One drawback to this material is that while the backbone of the EH scaffolds is formed from these hydrolytically degradable units, the use of the diacrylate end groups creates an additional carboxylic acid byproduct which can affect the local in vivo environment. These effects are minimal, however, making this polymer a strong candidate for biomedical applications (9,10,(12)(13)(14).…”