Controlled Release of Hepatocyte Growth Factor from MPEG-b-(PCL-ran-PLLA) Diblock Copolymer for Improved Vocal Fold Regeneration.

An in situ-forming gel system comprised of diblock copolymer formed from polyethylene glycol (PEG) and polycaprolactone (PCL) {MPEG-b-(PCL-ran-PLLA)} could be used in controlled drug delivery for tissue remodeling. The purpose of this study is to demonstrate favorable vocal folds (VF) regeneration by using MPEG-b-(PCL-ran-PLLA) diblock copolymers (C97L3; CL/LA ratio 97:3) incorporating hepatocyte growth factor (HGF). Gradual release of HGF from C97L3 is detected and biochemical properties of released HGF are maintained. A scar is made with microscissors on both VFs in 32 rabbits, followed by injection of HGF-only, C97L3-only, or HGF-C97L3 composite gel in the left side VF, while the right side VF is left untreated. In vivo fluorescence live imaging system demonstrates that C97L3 enables the sustained release of injected HGF in the scarred VF for 12 weeks. The histological analysis shows increased glycosaminoglycan including hyaluronic acid accumulation and decreased collagen deposition. Videokymographic analysis shows more favorable vibrations of HGF-C97L3 treated VF mucosa, compared to other treatment groups. In conclusion, the controlled HGF release helps to regulate extracellular matrix synthesis, and leads to the eventual functional improvement of the scarred VF.

Small intestine submucosa and mesenchymal stem cells composite gel for scarless vocal fold regeneration.

The purpose of this study is to demonstrate scarless vocal fold (VF) regeneration by using a composite gel composed of small intestine submucosa (SIS) and mesenchymal stem cells (MSCs). A scar was made with an electrocoagulator on both VFs in 24 rabbits, followed by injection of either MSCs, SIS, or MSCs-SIS composite gel in the right side VF, while the left side VF was left untreated. VF scars were evaluated with in vivo fluorescence live imaging system (IFLIS), endoscopy, histology, and videokymography (VKG) after eight weeks. IFLIS demonstrated that SIS enabled the MSCs to survive and be engrafted in the VF. The histological analysis showed increased hyaluronic acid accumulation and controlled collagen deposition by MSCs-SIS composite gel. VKG analysis showed more favorable vibrations of MSCs-SIS injected VF, compared to other treatment group. In conclusion, the injectable SIS supplied a niche for the MSCs to stably settle down in scarred VFs and helped to regulate ECM synthesis. The ECM remodeling underwent by the surviving MSCs eventually led to the functional improvement of the VF. The results of the present investigation suggest that SIS-MSCs composite gel is a plausible biomaterial for prolonged survival of MSCs in VFs and promotes scarless VF healing.