In vivo degradation rate of alginate–chitosan hydrogels influences tissue repair following physeal injury

Abstract

The physis is a cartilaginous tissue in children's long bones that is responsible for bone elongation. Physeal injuries can heal with bony repair tissue known as a “bony bar,” and this can cause growth deformities. Current treatments involve surgical resection of the bony bar and insertion of inert materials in hopes of preventing bony bar re‐formation and preserving bone elongation. However, these materials frequently fail and the bony bar commonly returns. This study investigated alginate–chitosan hydrogels as interpositional materials to block bony bar formation in a rat model of physeal injury. Further, biomaterial properties such as substrate stiffness, permeability, and degradation rate were studied. Different ratio alginate:chitosan hydrogels with or without calcium cross‐linking were tested for their inhibition of bony bar formation and restoration of the injured physis. Alginate:chitosan were mixed (a) 90:10 with calcium (90:10 + Ca); (b) 50:50 with calcium (50:50 + Ca); (c) 50:50 without calcium (50:50 − Ca); and (d) 50:50 made with irradiated alginate (IA) and without calcium. We found that repair tissue was determined primarily by the in vivo degradation rate of alginate–chitosan hydrogels. 90:10 + Ca had a slow degradation rate, prevented cellular infiltration, and produced the most bony bar tissue while having softer, more permeable material properties. IA had the fastest degradation, showed high cellular infiltration, and produced the most cartilage‐like tissue while having stiffer, less permeable material properties. Our results suggest that the in vivo biomaterial degradation rate is a dynamic property that can be optimized to influence cell fate and tissue repair in physeal injuries.

Emulsion-free chitosan–genipin microgels for growth plate cartilage regeneration

“…Low molecular weight chitosan (75–80% deacetylation, Sigma-Aldrich, St. Louis, MO, product number 448869) was purified as previously described. 20 In brief, the chitosan was dissolved at 1 wt% in 1% glacial acetic acid, filtered to 0.22 µm, and dialyzed in cellulose bags with a 3500 Da MW cutoff for 1 week in distilled water. The chitosan was then lyophilized and frozen until further use.…”

“…Sections in the middle of the injury site were stained using ABH (a composite stain of Alcian Blue, Hematoxylin, Orange G, Phloxine B, and Eosin Y), which has been used extensively in growth plate research and stains cartilage blue, bone orange to red, fibrous tissue pink, and the chitosan microgels dark red. 20,[25][26][27] While ABH stain cannot specifically stain for the chitosan microgels, they seem to appear as a dark red fibrous tissue which is not observed in the untreated group that does not receive chitosan microgels. Based on this dark red staining, the degradation of the chitosan microgels at each time point could be evaluated.…”

A Review of Recent Advances in Natural Polymer-Based Scaffolds for Musculoskeletal Tissue Engineering

“…The proposed hydrogel demonstrated significant controllable degradation that would inhibit bone growth deformities, and also it showed the ability for loading chondrogenic factors. Therefore, this scaffold can be a promising platform that improves physical injury repair [ 128 ]. To sum up, alginate has excellent biocompatibility and devisable potential with its functional groups; the limitations such as the strength and degradation of alginate are still the research priorities in this field.…”

Photopolymerization of Bio-Based Polymers in a Biomedical Engineering Perspective

“…However, residual alginate found within the defect site at 8 weeks post-implantation prevented complete bone regeneration. Tailoring biomaterial degradation rate is the first issue to be solved, as a fast in vivo degradation rate allows cell infiltration and, therefore, sustains tissue growth …”