Tough, Semisynthetic Hydrogels for Adipose Derived Stem Cell Delivery for Chondral Defect Repair

Abstract

Cell-based therapies have great potential to regenerate and repair injured articular cartilage, and a range of synthetic and natural polymer-based hydrogels have been used in combination with stem cells and growth factors for this purpose. Although the hydrogel scaffolds developed to date possess many favorable characteristics, achieving the required mechanical properties has remained a challenge. A hydrogel system with tunable mechanical properties, composed of a mixture of natural and synthetic polymers, and its use for the encapsulation of adipose derived stem/stromal cells (ASCs) is described. Solutions of methacrylated chondroitin sulfate (MCS) are mixed with solutions of acrylate-poly(trimethylene carbonate)-b-poly(ethylene glycol)-b-poly(trimethylene carbonate)-acrylate (PEG-(PTMC-A) ) in phosphate buffered saline and crosslinked via thermally initiated free radical polymerization. The hydrogel compressive equilibrium moduli and toughness are readily tailored by varying the concentration of the pre-polymers, as well as the molecular weight of the PEG used to prepare the PEG-(PTMC-A) . Two peptide sequences, GVOGEA and GGGGRGDS, are individually conjugated to the MCS to facilitate cell binding. The presence of the peptide ligands yields high ASC viability and long term metabolic activity following encapsulation in hydrogels prepared using the thermal initiator system. Overall, these hydrogels show promise as a minimally invasive ASC delivery strategy for chondral defect repair.

Near-Infrared-Triggered in Situ Gelation System for Repeatedly Enhanced Photothermal Brachytherapy with a Single Dose

“…, the tumor) to allow long-term local retention of therapeutic agents with sustained drug release. − We thus hypothesize that radioisotope-encapsulated hydrogels that can undergo sol-to-gel transformation within the tumor may be an attractive approach for easy-to-operate brachytherapy. There have been different ways to trigger the in situ formation of hydrogels within the body after injection of liquid solution, such as light, − redox, − and specific enzymes. , Among those strategies, the light-induced gelation method by using photoinitiator to trigger polymerization is attractive because it can be controlled with great temporal and spatial precision. − Unfortunately, most photoinitiators are excited by short-wavelength light sources with limited tissue-penetration depth. − To realize an efficient form of brachytherapy, it would thus be interesting to develop near-infrared (NIR) light-activable hydrogel systems that are able to homogeneously restrain therapeutic radioisotopes in the tumor for the long term in a highly controllable manner and hopefully, in the meantime, could overcome hypoxia-associated radiation resistance for solid tumors …”

Can we Achieve the Perfect Injectable Scaffold for Cell Therapy?

“…Yet, in the past 10 years, significant improvement has arisen on that matter. Injectable, cell-encapsulating interpenetrating polymer networks, composed of two polymer networks that can independently and simultaneously crosslink to form hydrogels in a cell-friendly manner, have been developed [ 15 , 16 ]. Thermosensitive hydrogels, which undergo a sol-gel transition upon heating to body temperature, can now achieve high mechanical properties in situ thanks to the use of new gelling agents combinations [ 17 ].…”

Chitosan/aminoacid hydrogels with antimicrobial and bioactive properties as new scaffolds for human mesenchymal stem cells culture applicable in wound healing

“…The number of cells was evaluated at the moment of plating and at culture termination. Population doubling was calculated using Equation (1): (1) where N h number of cells on the day of culture termination, N 0 number of plated cells. Photographic documentation was also prepared in order to verify whether contact growth inhibition occurred.…”

“…Some of the most significant parameters when designing a hydrogel scaffold are swelling, mechanical properties and material degradation in time, which are strictly correlated with the cross-linked structure of hydrogel being controlled by various manufacturing conditions [11]. The hydrogel scaffolds that are currently available have many advantages but obtaining the required mechanical properties still constitutes a challenge [1]. Many polymers used in the production of hydrogel are natural, e.g.…”