Tri-Layered Doxycycline-, Collagen- and Bupivacaine-Loaded Poly(lactic-co-glycolic acid) Nanofibrous Scaffolds for Tendon Rupture Repair

Abstract

Achilles tendon rupture is a severe injury, and its optimal therapy remains controversial. Tissue engineering scaffolds play a significant role in tendon healing and tissue regeneration. In this study, we developed tri-layered doxycycline/collagen/bupivacaine (DCB)-composite nanofibrous scaffolds to repair injured Achilles tendons. Doxycycline, collagen, and bupivacaine were integrated into poly(lactic-co-glycolic acid) (PLGA) nanofibrous membranes, layer by layer, using an electrospinning technique as healing promoters, a 3D scaffold, and painkillers, respectively. After spinning, the properties of the nanofibrous scaffolds were characterized. In vitro drug discharge behavior was also evaluated. Furthermore, the effectiveness of the DCB–PLGA-composite nanofibers in repairing ruptured Achilles tendons was investigated in an animal tendon model with histological analyses. The experimental results show that, compared to the pristine PLGA nanofibers, the biomolecule-loaded nanofibers exhibited smaller fiber size distribution and an enhanced hydrophilicity. The DCB-composite nanofibers provided a sustained release of doxycycline and bupivacaine for over 28 days in vivo. Additionally, Achilles tendons repaired using DCB-composite nanofibers exhibited a significantly higher maximum load-to-failure than normal tendons, suggesting that the biomolecule-incorporated nanofibers are promising scaffolds for repairing Achilles tendons.

Electrospun Nanofibrous Composite Membranes for Long‐Term Release of Celecoxib for Achilles Tendon Reconstruction Following Injury

“…The maximum load ( Figure ) and sample diameter of the normal tendon specimen (control group), tendon specimens treated with the CCBP combination (CCBP group), and those treated with the DCBP combination [ 24 ] (DCBP group) were compared. The average diameter of the center of the tendon was significantly larger in the CCBP group than in the control (4.73 ± 0.21 vs 2.07 ± 0.42, p < 0.001).…”

“…Nanofibrous scaffolds combining doxycycline, collagen, bupivacaine, and PLGA (referred to as DCBP combination scaffolds) have previously been used to repair injured Achilles tendons in rats through local drug delivery of pharmaceuticals. [ 24 ] The tendon treated with the drug‐containing DCBP scaffold exhibited strong growth factor expression and superior maximal load‐to‐failure ratios compared to normal tendon healing characteristics. Additionally, the analgesic effect of the co‐incorporated bupivacaine enabled the rats to return rapidly to normal activities after surgery.…”

Advancements in scaffold for treating ligament injuries; in vitro evaluation

“…The bFGF-PLGA scaffold showed significantly better mechanical properties and advantages over PLGA alone. [161] ASC, adipose-derived mesenchymal stem cell; bFGF, basic fibroblast growth factor; CNC, cellulose nanocrystal; COL, collagen; CS, chitosan; FDA, Food and Drug Administration; GAG, glycosaminoglycan; GT, gelatin; LPP, leak point pressure; MRCT, massive rotator cuff tears; MSC, mesenchymal stem cell; PCL, poly(ε-caprolactone; PGA, polyglycolic acid; PLCL, poly(L-acid-co-caprolactone); PLGA, poly(lactide-co-glycolic acid); PLLA, poly(L-lactic acid); β-TCP, β-tricalcium phosphate.…”

Biodegradable Polymer Electrospinning for Tendon Repairment

“…A multilayer nanofiber scaffold is usually made of electrospun high-conductivity solution. The polymer solution mixed with salt or bioactive molecules can adjust the fiber structure and function [ 76 ]. One multiscale fiber scaffold was composed of orderly arranged PCL microfibers/collagen bFGF nanofibers (mPCL-nCol-bFGF), and coated with sodium alginate to inhibit the surrounding adhesion.…”