Adeno-Associated Virus-Encapsulated Alginate Microspheres Loaded in Collagen Gel Carriers for Localized Gene Transfer.

This work reports localized in vivo gene transfer by biodegradation of the adeno-associated virus-encapsulating alginate microspheres (AAV-AMs) loaded in collagen gel carriers. AAV-AMs are centrifugally synthesized by ejecting a mixed pre-gel solution of alginate and AAV to CaCl2 solution to form an ionically cross-linked hydrogel microsphere immediately. The AAV-AMs are able to preserve the AAV without diffusing out even after spreading them on the cells, and the AAV is released and transfected by the degradation of the alginate microsphere. In addition, AAV-AMs can be stored by cryopreservation until use. By implanting this highly convenient AAV-encapsulated hydrogel, AAV-AMs can be loaded into collagen gel carriers to fix the position of the implanted AAV-AMs and achieve localized gene transfer in vivo. In vivo experiments show that the AAV-AMs loaded in collagen gel carriers are demonstrated to release the encapsulated AAV for gene transfer in the buttocks muscles of mice. While conventional injections caused gene transfer to the entire surrounding tissue, the biodegradation of AAV-AMs shows that gene transfer is achieved locally to the muscles. This means that the proposed AAV-loaded system is shown to be a superior method for selective gene transfer.

A unique case of high-grade myofibroblastic sarcoma initially presenting with oral symptoms.

High-grade myofibroblastic sarcoma is a rare mesenchymal tumor with a high recurrence and metastatic rate. Few cases of high-grade myofibroblastic sarcomas have been reported. Herein, we report a rare case of undifferentiated, high-grade myofibroblastic sarcoma with an unclear primary site, initially presenting with oral symptoms. High-grade myofibroblastic sarcoma was diagnosed following an excisional biopsy of a gingival tumor. After this excisional biopsy, systemic imaging revealed multiple metastases in the tonsil, lung, liver, kidney, and eye. The patient underwent two cycles of chemotherapy (doxorubicin). During follow-up, the tumor progressed rapidly and metastasized to the skin of the head and neck. The patient expired three months after the initial examination.

Osteopontin-derived synthetic peptide SVVYGLR has potent utility in the functional regeneration of oral and maxillofacial skeletal muscles.

Oral and maxillofacial skeletal muscles are critical for oral motor functions, and severe damage to these muscles by trauma or surgery may lead to persistent functional impairment. This study investigated the effects of SVVYGLR (SV) peptide, a thrombin-cleaved osteopontin-derived motif, on histopathological wound healing and functional repair after severe injury of skeletal muscles. A rat model of volumetric muscle loss bilateral masseter muscle was developed. A single dose of SV-peptide or phosphate-buffered saline (PBS) was separately injected into the injured muscle belly. Histopathological and functional analyses were performed 1-8 weeks after the treatment. Behavioral analysis during free-feeding revealed that the feeding rate markedly increased in the SV-peptide group, in contrast, the PBS group showed fewer changes after the injury. Electromyogram recordings from injured muscles demonstrated amplification of rectified burst activity over time accompanied by increased maximal amplitude and duration in the SV-peptide group, in contrast, the PBS group showed moderate changes. A lissajous figure for bilateral masseter muscle activities also revealed superior functional recovery by the SV-peptide treatment. The SV-peptide also facilitated regeneration of muscles composed of matured myofibers with a greater diameter compared to the PBS group. In addition, granulation in the earlier period and fibrosis in the later period of wound healing were significantly inhibited by the SV-peptide treatment but not by the PBS treatment. Therefore, local application of the SV-peptide could help facilitate regeneration of muscles, inhibition of fibrosis, and improvement of functional impairment of oral and maxillofacial skeletal muscles damaged by severe trauma or surgery.