3D Tissue Engineered Supramolecular Hydrogels for Controlled Chondrogenesis of Human Mesenchymal Stem Cells

Abstract

Despite a wide investigation of hydrogels as an artificial extracellular matrix, there are few scaffold systems for the facile spatiotemporal control of mesenchymal stem cells (MSCs). Here, we report 3D tissue engineered supramolecular hydrogels prepared with highly water-soluble monofunctionalized cucurbit[6]uril-hyaluronic acid (CB[6]-HA), diaminohexane conjugated HA (DAH-HA), and drug conjugated CB[6] (drug-CB[6]) for the controlled chondrogenesis of human mesenchymal stem cells (hMSCs). The mechanical property of supramolecular HA hydrogels was modulated by changing the cross-linking density for the spatial control of hMSCs. In addition, the differentiation of hMSCs was temporally controlled by changing the release profiles of transforming growth factor-β3 (TGF-β3) and/or dexamethasone (Dexa) from the hydrolyzable Dexa-CB[6]. The effective chondrogenic differentiation of hMSCs encapsulated in the monoCB[6]/DAH-HA hydrogel with TGF-β3 and Dexa-CB[6] was confirmed by biochemical glycosaminoglycan content analysis, real-time quantitative PCR, histological, and immunohistochemical analyses. Taken together, we could confirm the feasibility of cytocompatible monoCB[6]/DAH-HA hydrogels as a platform scaffold with controlled drug delivery for cartilage regeneration and other various tissue engineering applications.

Integrating Mechanical and Biological Control of Cell Proliferation Through Bioinspired Multieffector Materials

“…However, dual combinations of these GFs show a synergic effect, being possible to simultaneously induce migration and collagen deposition when using VEGF and BMP-2, and observing a greatest influence on tissue deposition when combining TGF-3 and BMP-2 (113,114) . Furthermore, engineered hydrogels can be used to stimulate cartilage regeneration (115) . Considering that…”

“…MSCs are a promising source for cartilage regeneration and that TGF- family has a key role in the chondrogenesis process of MSCs, Jung and collaborators have designed Cyclodextrin(CD)-and Cucurbituril(CB)-based hydrogels able to deliver TGF- through a spatiotemporal control in vivo, showing again promising results (115) .…”

“…Increased the formation of new bone in the porosities of a canine implant (151) TGF- Cyclodextrin(CD)-and Cucurbituril(CB)-based hydrogels Effective chondrogenic differentiation (115) VEGF PEG-based hydrogels Stimulates cell migration and proliferation and maintain cell viability (116,117) VEGF Embedded in gelatine-like gels…”

Synthesis of linear cucurbit[7]uril pendent copolymers through radical polymerization: Polymers with ultra‐high binding affinity

“…[1][2][3] Their anchoring onto macromolecules offers further opportunities to expand their applications, [8][9][10] however there are currently few examples of such reports. [11][12][13][14][15][16] The relatively few reports are likely as a result of the difficulties encountered in the modification of CBs; this problem persisted until Kim's group reported the functionalization of CBs with a facile oxidation method in 2003. 17 Through oxidization of CBs with persulfate, hydroxyl groups -which are suitable for further functionalization-could be introduced at their peripheries.…”

“…[11][12][13] The eminent binding properties of CB[6] allow these polymer nanocapsules to be decorated easily with targeting and labeling groups through host-guest interactions. Recently, allyl functionalized CB[6] and CB [7] were grafted on to hyaluronate through a thiol-ene click reaction, [14][15][16] and where employed for theranostic systems and tissue engineering applications. In addition of the oxidation method, Isaacs's group developed a different method to synthesize CB derivatives.…”