Biomolecules‐releasing click chemistry‐based bioadhesives for repairing acetabular labrum tears

Abstract

Currently, there are no effective clinical or experimental treatments to fully restore the function of the torn acetabular labrum. To fill the gap, here, we report the finding of progenitor cells in labral tissue, which can be recruited and stimulated to repair torn acetabular labral tissue. This study aimed to develop a biomolecule releasing bioadhesive which can speed up labral tissue healing by eliciting autologous labral progenitor cellular responses. A click chemistry‐based bioadhesive, capable of releasing biomolecules, was synthesized to exert ~3× adhesion strength compared with fibrin glue. Via the release of platelet‐derived growth factor (PDGF), the adhesive was shown to actively recruit and stimulate the proliferation of labral progenitor cells to the tear sites and within the adhesive. Finally, the ability of this biomolecules‐releasing adhesive designed to promote labral tissue regeneration was evaluated using discarded human acetabular labrum tissue compared with surgical suture ex vivo. Histological analysis shows that PDGF‐releasing bioadhesive yielded significantly more labrum cell responses and extracellular matrix protein (proteoglycan and collagen) production at the tear tissue site than surgical suture controls. The results confirm that the new PDGF‐releasing bioadhesive can activate the responses of autologous labral progenitor cells to significantly improve labral tissue regeneration. Clinical significance: These PDGF‐releasing bioadhesives may serve as a new and effective tool for repairing and regenerating acetabular labrum tears.

Mechanical and Biological Evaluation of Melt-Electrowritten Polycaprolactone Scaffolds for Acetabular Labrum Restoration

“…While tissue-engineering applications involve cell seeding and ex vivo growth of a labrum-like tissue, cell-free engineered grafts require cell migration to the reconstruction or repair site to create a repair tissue in vivo. One possible solution to attract present cells could be the functionalization of the scaffold surface with a growth factor, such as PDGF, which was recently shown to attract labrum progenitor cells to repair sites [ 47 ]. Cells on the grid-like structure (250/40) grew along the fibres and were not able to bridge the comparably large pores of 250 µm.…”

Biomolecule‐releasing bioadhesive for glenoid labrum repair through induced host progenitor cell responses

“…The CS bioadhesives were synthesized using previously published methods 17,23 . Two precursors, CS‐Tz and CS‐TCO, were produced through carbodiimide crosslinking between primary amine groups on the CS polymer backbone (low molecular weight [MW], Sigma‐Aldrich) and N ‐hydroxysuccinimide (NHS) groups in tetrazine‐NHS (Tz; Click Chemistry Tools) and trans ‐cyclooctene‐NHS ester (TCO; Click Chemistry Tools).…”

“…The degradation curve was generated by calculating the % initial weight remaining at each time point using the following equation: ( W t / W 0 ) × 100%. Next, the PDGF‐releasing property of the CS adhesives was characterized as documented earlier 17 . Briefly, adhesives were loaded with PDGF‐AB (Shenandoah Biotechnology; 2 µl and 0.2 mg/ml) before incubation in 1 ml PBS.…”

“…Despite these exciting advancements, similar strategies for labral tear regeneration have not yet been investigated. By analyzing the cells inside and isolated from human acetabular labrum tissue, we identified the presence of progenitor cells (CD90+/CD105+) 17 . Additionally, these cells can be recruited by platelet‐derived growth factor (PDGF) and then differentiated into fibrochondrocytes in vitro, using a high‐density cell pellet model 17 …”

“…Recently, a novel injectable click chemistry‐based chitosan (CS) bioadhesive, developed with fast gelation time and minimal cellular toxicity, has been shown to accelerate wound healing in a mouse skin incision model—faster than fibrin glue 23 . Additionally, previous studies have shown that CS adhesives are able to reattach labral tissue with better mechanical force than commercially available fibrin glue 17 . In addition, PDGF‐releasing CS adhesives were found to promote the recruitment of endogenous progenitor cells and increase the production of collagen type II (COL2) and glycosaminoglycan (GAG) in human acetabular labrum tissue 17 .…”