Schematic illustration of the crosslinking reaction between human bone marrow nesenchymal stem cell (hBMSC)-laden microgel and between the microgels and the surrounding tissue mimic via a 4-arm poly ethylene glycol-succinimidyl glutaramide (PEG-NHS).Articular cartilage is the load bearing tissue found at the end of long bones. Upon damage or degeneration, cartilage is unable to self-heal adequately. Current clinical approaches to regenerate articular cartilage provide only a temporary solution, failing at long term. Researchers in this field continuously look for alternatives to these methods and scaffold supported stem cell therapies appear to be the most promising approach. However, the development of scaffold materials capable of rapid integration with the surrounding native cartilage and of promoting the formation of stable and functional tissues still remains elusive. In order to overcome these issues, researchers from Monash University, CSIRO Manufacturing and ETH Zurich, have developed cell-laden based microgels that rapidly integrate with the host tissue and create a higher order cartilage-like structures. [Li et al., Acta Biomateralia (2018), doi.org/10.1016/j.actbio.2018.07.015].
Fluorescent microscopy images showing the formation of higher order tissue-like structures on the novel microgels (NHSA-microgels) as compared to traditional dispersed-microgels (D-microgels).“We’re very excited by this project because of the great improvement in chondrogenesis in the microgels compared to bulk hydrogels and the ability to bond the microgels, both to each other and to external matrix. We think this provides an important step towards the future use of this system for cartilage repair”, explains Frith.
The team used a microfluidic device that creates cell-laden gelatin-based microgels that readily assemble via blue-light irradiation. The microgels could then be injected on the damaged area and rapidly crosslink with each other and the surrounding tissue via addition of a 4-arm polymer based on PEG-NHS (poly(ethylene glycol)-succinimidyl glutaramide). Thus, the system presents an easy approach to the effective and rapid integration of microgels to the host tissue.
In-vitro tissue engineering shows that cultures of PEG-NHS treated microgels (NHSA-microgels) present a higher order structure provided by the rapid assembly of the gels as compared to non-crosslinked dispersed microgels (D-microgels). In addition, NHSA-microgels also show a greater potential to promote chondrogenic differentiation at a gene level when compared to traditional bulk hydrogels. These results, together with histological and immunofluorescence analyses suggests that these novel NHSA-microgel systems outperform traditional hydrogel systems on their cartilage regeneration potential.
The greater potential of the NHSA-microgels on stem cells differentiation and the ease of utilization via injection into the damaged area results in a system that holds a promising future for clinical therapy.
Cell-laden microgel assembly provides formed tissues with higher order and a rapid bonding to the native environment offering the possibility to be exploited in other tissue engineering and regenerative medicine applications.