Controlling Rigidity and Degradation of Alginate Hydrogels via Molecular Weight Distribution

Abstract

The mechanical rigidity and degradation rate of hydrogels utilized as cell transplantation vehicles have been regarded as critical factors in new tissue formation. However, conventional approaches to accelerate the degradation rate of gels deteriorate their function as a mechanical support in parallel. We hypothesized that adjusting the molecular weight distribution of polymers that are hydrolytically labile but capable of forming gels would allow one to alter the degradation rate of the gels over a broad range, while limiting the range of their elastic moduli (E). We investigated this hypothesis with binary alginate hydrogels formed from both ionically and covalently cross-linked partially oxidized (1% uronic acid residues), low [molecular weight (MW) approximately 60,000 g/mol] and high MW alginates (MW approximately 120,000 g/mol) in order to examine the utility of this approach with various cross-linking strategies. Increasing the fraction of low MW alginates to 0.50 maintained a value of E similar to that for the high MW alginate gels but led to faster degradation, irrespective of the cross-linking mode. This result was attributed to a faster separation between cross-linked domains upon chain breakages for the low MW alginates, coupled with their faster chain scission than the high MW alginates. The more rapidly degrading oxidized binary hydrogels facilitated the formation of new bone tissues from transplanted bone marrow stromal cells, as compared with the nonoxidized high MW hydrogels. The results of these studies will be useful for controlling the physical properties of a broad array of hydrogel-forming polymers.

Spatiotemporal control over growth factor signaling for therapeutic neovascularization☆

“…Varying the composition of synthetic polymer such as PLGA can control the degradation rate to produce differential VEGF release profiles [140]. Natural polymer like alginate can be oxidized, irradiated, crosslinked or varied in the molecular weight distribution [141][142][143] to affect the degradation rate. Reversible binding of the factors to the alginate vehicles is also often used to modulate the factor release rate [144].…”

Growth factor delivery for oral and periodontal tissue engineering

“…In addition, the development of both naturally derived and synthetic materials allows the degradation properties to be controlled by the composition and ratios of compounds that comprise the material. A key advantage of this, particularly with more recently developed polymers, is that these properties can be tailored to meet the specific needs of the application with regard to how long one desires to have the material maintained [34,[41][42][43].…”

Application of Sodium Alginate Hydrogel

“…Consequently, increasing the degree of oxidation increases degradability of the resulting alginate gel in physiological conditions [13]. Another useful way of alginate chemical modification is to go within the process of sulfating that can be prepared by formamide chlorosulfuric acid interaction with alginate [14]. This process delivers a structural like heparin(Alginate) and thus promotes an efficient compatibility of the blood.…”

“…Knowledge of developmental biology mechanisms, specifically those involving gene regulation of cell differentiation and tissue specification, can be integrated with other biological fields to help solve major questions that still exist in those areas [24].Examples of in vitro culture systems that have employed the tissue engineering approach include models for ovarian follicle [25][26] and embryo development [26][27], as well as in vitro organ models such as kidney [31], cardiac [52], skin [53], and oviduct models [28]. Human skin models, in particular, have served as in vitro test systems for pharmaceutical research [29], and cardiac tissue models have provided a means for electrophysiological studies of the heart [30], a complicated task to evaluate by in vivo measures. In addition, in vitro tumor models have recently become highly appealing for studying the efficiency of chemotherapy drugs [31], as well as factors involved in tumor initiation and progression [32].…”