An injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells

For chronic wounds, the delivery of stem cells in spheroidal structures can enhance graft survival and stem cell potency. We describe an easy method for the 3D culture of adipose-derived stem/stromal cells (ASCs) to prepare a ready-to-use injectable. We transferred suspensions of monolayer-cultured ASCs to a syringe containing hyaluronic acid (HA) gel, and then incubated the syringe as a 3D culture vessel. Spheroids of cells formed after 12 h. We found that 6 × 106 ASCs/ml in 3% HA gel achieved the highest spheroid density with appropriate spheroid sizes (20–100 µm). Immunocytology revealed that the stem cell markers, NANOG, OCT3/4, SOX-2, and SSEA-3 were up-regulated in the ASC spheroids compared with those in nonadherent-dish spheroids or in monolayer cultured ASCs. In delayed wound healing mice models, diabetic ulcers treated with ASC spheroids demonstrated faster wound epithelialization with thicker dermis than those treated with vehicle alone or monolayer cultured ASCs. In irradiated skin ulcers in immunodeficient mice, ASC spheroids exhibited faster healing and outstanding angiogenic potential partly by direct differentiation into α-SMA+ pericytes. Our method of 3D in-syringe HA gel culture produced clinically relevant amounts of ready-to-inject human ASC microspheroids that exhibited superior stemness in vitro and therapeutic efficacy in pathological wound repair in vivo

A Case of Microstomia Subsequent to Toxic Epidermal Necrolysis Surgically Treated by Simple Technique

Summary: Toxic epidermal necrolysis (TEN) is a rare but severe adverse dermatitis that is an autoimmune reaction to drugs such as nonsteroidal anti-inflammatory drugs. TEN most severely affects the mucous membranes including the mouth and could develop into microstomia; however, microstomia in relation to TEN has rarely been reported in the literature. We describe an adult female patient who developed microstomia due to scar contracture of the bilateral oral commissures subsequent to TEN and was successfully treated by a simple surgical technique consisting solely of transverse incision of the commissure and longitudinal closure

Muscular Pedicled Lateral Chest Composite Flap—A New Nonmicrosurgical Option for Forearm Salvage

Summary: Posttraumatic upper or lower limb salvage is still challenging. Under difficult situations in which only one vessel supplies the hand or foot, free microvascular reconstruction might damage not only the transferred tissue but also the terminal hand or foot. Two cases of incomplete amputation of the unilateral forearm with large radius bone and soft tissue loss were reconstructed using a newly-refined pedicled osteomyocutaneous flap including vascularized rib, lateral part of the latissimus dorsi muscle, and skin as a lateral chest flap. After insetting of the flap, the transferred limb is fixed with a soft bandage, and the flap is divided no less than 4 weeks after the first operation. The flap completely survived, and bone union between the rib and radius was observed. Although our treatment needed a two-stage procedure, safe and secure reconstruction with an appropriate amount of tissue for salvage was accomplished

Semipermanent Volumization by an Absorbable Filler: Onlay Injection Technique to the Bone

Background: Hyaluronic acid (HA) fillers have become the most popular tool for wrinkle treatment and volumization, although HA is generally absorbed within 6–12 months and requires repeated treatments to maintain the effects. Methods: HA was injected onto the bone for volumization with a small 30-gauge needle to examine the long-lasting effects. Of the 63 Japanese patients with 97 treated sites followed up more than 12 months, 51 had HA injections for cosmetic purposes and 12 were treated for reconstructive volumization of facial deformity such as localized scleroderma and postsurgical bony deformity. Treated sites included the forehead, temple, nasal root, mentum, tear trough, and infraorbital sulcus. Results: After long-term follow-up (12–93 months, mean = 21.6), persistent volumizing effects were observed in most patients. In fact, 86.6% of the treated sites showed >50% volume retention and 49.5% showed >75% retention. Magnetic resonance imaging analyses revealed that the injected space was well maintained, capsulated, and filled with heterogeneous content. Magnetic resonance imaging quantitative T2 maps indicated that much of the injected HA was replaced with other materials. Together with clinical inspection, these findings suggest that onlay injection of HA on the bone induced formation of capsule, fibrosis, and/or calcification/ossification, which contributed to persistent volumization. Conclusions: Semipermanent volumizing effects can be achieved by HA injection if the target area has an underlying bony floor. Periosteal stem cells may be activated by HA injection and may contribute to persistent volumizing effects. This treatment may be a much less invasive alternative to fat or bone grafting