Amylopectin Multiple Aldehyde Crosslinked Hydrogel as an Injectable and Self‐Healing Cell Carrier for Bone Tissue Engineering

Abstract

linkages formed between aldehyde and amine functional groups offer unique properties including self-healing and injectability in the so-called dynamic hydrogels. [1][2][3][4][5] Hence, Schiff base-based dynamic hydrogels have found application in regenerative medicine, drug delivery, [6,7] wound dressing. [8,9] Cell delivery for regenerative medicine is one of the marvelous applications of dynamic hydrogels based on natural polymers which are addressed in recent scientific reports. For example, chitosan crosslinked using polyethylene glycol dibenzaldehyde through Schiff base linkages were found to be an injectable and self-healing hydrogel. Such prepared hydrogels have been used as a cell delivery vehicle for encapsulation of neural stem cells for promoting nerve regeneration. [3] Another self-healing/injectable hydrogel was reported as a cell carrier for cardiac cell therapy by Schiff base linkages between chitosan chains and polyethylene glycol dibenzaldehyde. [10] As another example, a self-healing and injectable hydrogel cell carrier for myoblast cell therapy was reported prepared by Schiff base linkages between N-carboxyethyl chitosan and dextran-graft-aniline tetramer-graft-4-formylbenzoic acid. [11] Such studies have been focused on the formation of Schiff base linkages via benzaldehyde derivatives for crosslinking chitosan as the amine sharing part and the obtained hydrogels support both injectability and self-healing characteristics as the cell delivery systems.On the other hand, there are some reports on fabrication of injectable and self-healing dynamic hydrogels based on Schiff base linkages by aliphatic aldehyde sharing parts for cell delivery applications. For example, an injectable and self-healing hydrogel was prepared via formation of Schiff base linkages between N-succinyl-chitosan and chondroitin sulfate multiple aldehyde. The reported hydrogel was used for encapsulation of Hela cells. [12] Also, a hydrogel with mentioned characteristics was reported which was fabricated by the formation of Schiff base linkages between N-carboxyethyl chitosan and oxidized sodium alginate and was used as a cell carrier for neural stem cells. [13] Moreover, another injectable and self-healing hydrogel Despite excellent processing and biological properties of gelatin for use as a cell carrier, none of the gelatin-based hydrogel cell carriers reported to date offer all characteristics including quick formation, injectability, self-healing, and durability, which are simultaneously required for an ideal system. Here, a gelatin-based hydrogel with dynamic Schiff base linkages, so-called "dynamic hydrogel," as an injectable cell carrier consisting of gelatin and amylopectin multiple aldehyde (AMPA), with all the required characteristics is reported. Biocompatibility and osteoinductivity of the hydrogel are verified through the culture of human bone marrow-derived mesenchymal stem cells (hBMSCs). As live/dead results show, hBMSCs are alive and highly viable ≈85-90% within the hydrogel after 5 days. According to bromodeo...

Progress in Gelatin as Biomaterial for Tissue Engineering

“…Specifically, gelatin amino groups were combined with amylopectin aldehyde groups that resulted in hydrogels capable of recovering their shape and maintaining their rheological properties. Along with that, they confirmed their applicability in bone tissue regeneration as scaffolds presenting osteoinductive properties [70].…”

“…Another strategy that has gained importance recently relies on designing self-healing hydrogels. The latter reveals itself to be an interesting alternative in highly loaded tissues, such as bone, owing to their properties of regeneration after collapse [70][71][72]. In this process, gelatin's characteristics support formulating hydrogels that are dynamically bonded, which give rise to systems that can be recomposed upon their breakup.…”

“…Particularly, aromatic molecules of this polypeptide allow for the generation of dynamic bonds, by means of host-guest physical interactions [73]. Likewise, gelatin amino groups permit interaction with aldehyde groups and, therefore, form dynamic bonds [70][71][72]. Based on the latter, Vahedi et al engineered a gelatin-based self-healing and injectable hydrogel.…”

Poly-tetrahydropyrimidine Antibacterial Hydrogel with Injectability and Self-Healing Ability for Curing the Purulent Subcutaneous Infection

“…After 24 h, the solvent was removed with a rotary evaporator, and the crude product was precipitated by ether to obtain P­(DMA-VA) (8.64 g, 78%) as a yellowish powder. The aldehyde content of products was further determined by a modified titration method . In brief, 20 mL of hydroxylamine hydrochloride methanol solution (20 mg/mL) and 0.2 g of P­(DMA-VA) were mixed first, with 0.1% thymol blue ethanol solution (one drop) as an indicator.…”

“…The aldehyde content of products was further determined by a modified titration method. 37 In brief, 20 mL of hydroxylamine hydrochloride methanol solution (20 mg/mL) and 0.2 g of P(DMA-VA) were mixed first, with 0.1% thymol blue ethanol solution (one drop) as an indicator. The mixture turned pink after 10 min of stirring before the test, then titrated with standard sodium hydroxide solution (0.03 mol/L), and the calibration was recorded when the solution turned yellow without changing for 30 s. The aldehyde concentration of P(DMA-VA) was calculated by the following formula.…”