A rapid crosslinking injectable hydrogel for stem cell delivery, from multifunctional hyperbranched polymers via RAFT homopolymerization of PEGDA

Abstract

Stem cell therapies have been attracted much attention for the last few decades in the field of regenerative medicine and tissue engineering. 3-dimensional (3D) microenvironment surrounding the transplanted stem cells plays essential roles that influence the cell fate and behaviors. Thus advanced functional biomaterials and extracellular matrix (ECM) replacements with adjustable chemical, mechanical and bioactive properties are requisite in this field. In this study, PEG-based hyperbranched multifunctional homopolymers were developed via RAFT homopolymerization of the divinyl monomer of poly(ethylene glycol) diacrylate (PEGDA). Due to its high degree of multi-acrylate functionality, the hyperbranched polyPEGDA can rapidly crosslink with a thiolated hyaluronic acid at physiological condition and form an injectable hydrogel for cell delivery. In addition, by simply varying the synthesis recipe such as the reaction time and the ratio of the monomer to chain transfer agent (CTA), tunable polymer molecular weight, acrylate functionality degree and the cyclized/hyperbranched polymeric architecture can be finely controlled in one-step reaction. The gelation speed and the mechanical properties of this hydrogel can be easily adjusted by altering the crosslinking conditions. Rat adipose-derived stem cells (rASC) were embedded into the in situ crosslinked hydrogels, and their cellular behavior such as the morphology, viability, metabolic activity and proliferation were fully evaluated. The results suggested the hydrogel maintained good cell viability and be able to easily modify with other bioactive signals, which provide this injectable hydrogel delivery system a decent potential for polymeric biomaterial and tissue regeneration applications.

Functional‐Polymer Library through Post‐Polymerization Modification of Copolymers Having Oleate and Pentafluorophenyl Pendants

“…It is difficult to make polymers containing side‐chain methacrylate from dimethacrylate‐based monomers, because of formation of cross‐linked polymeric gels or hyperbranched polymers . Herein, the benefit of trans ‐esterification reaction was proven by incorporation of methacrylate moieties into the side chain of P(MAEO‐ co ‐PFPMA) copolymer by treating CP3 with 2‐hydroxyethyl methacrylate (HEMA).…”

“…[44] It is difficult to make polymers containing side-chain methacrylate from dimethacrylate-basedm onomers, because of formation of cross-linked polymeric gels or hyperbranched polymers. [45,46] Herein, the benefit of trans-esterification reaction was provenb yi ncorporation of methacrylate moieties into the side chain of P(MAEO-co-PFPMA) copolymerb yt reating CP3 with 2-hydroxyethyl methacrylate( HEMA). The resultant polymer was characterizedb yt he 1 HNMR spectrum, in which signals for CH 2 =C(CH 3 )À (2 H) protons appeared at 5.12 and 6.12 ppm ( Figure S11B of the Supporting Information).…”

Injectable scaffolds: Preparation and application in dental and craniofacial regeneration

“…Novel methods including chemo-selective crosslinking strategies (e.g. click chemistry) are designed to produce controlled crosslinking of hydrogels in situ under physiological conditions without toxic additives [120, 121]. …”

Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine

“…Hydrogel–host interactions may be decoupled from the delivery process through a needles or catheter by using shear‐thinning hydrogels . Other methods to induce crosslinking with macromolecules to form a hydrogel include chemical crosslinking by click chemistry, Michael addition, Schiff base reaction, and Diels–Alder reaction . Compared with physical crosslinking processes, chemical crosslinking provides better control in mechanical strength and degradation.…”