Jemin Jeremy Chae

Photoactivated Composite Biomaterial for Soft Tissue Restoration in Rodents and in Humans

Photoactivated composite poly(ethylene glycol)–hyaluronic acid biomaterials demonstrate enhanced physicochemical properties for facial soft tissue reconstruction. Photogenic Polymers Can Fix the Flaws Some people just love the spotlight; apparently, some polymers do too. Here, Hillel et al. introduce a class of composite polymers that react favorably to light by crosslinking within minutes. These polymers, composed of synthetic poly(ethylene glycol) (PEG) and natural hyaluronic acid (HA), have been developed for reconstructing facial soft tissue. Deformities in craniofacial soft tissue are a clinical challenge because even small defects can have a major impact on a person’s social behavior and psychological well-being. Hillel and colleagues created a polymeric composite that can be injected into the damaged site, massaged into shape, and then crosslinked in situ with light. A transdermal light exposure method would allow clinicians to inject a liquid polymer, rather than surgically inserting already-polymerized material. First, the authors designed an array of light-emitting diodes to penetrate up to 4 mm of human skin (both light and dark) without any painful side effects. A 2-min exposure to light was enough to crosslink the PEG-HA material under the skin. Next, the polymer was tailored to closely match the elastic properties of native soft tissues, such as human fat. Various amounts of PEG and concentrations of HA were tested, with the authors arriving at an optimal combination of 100 mg PEG and 24 mg/ml HA. When polymerized subcutaneously in rats, the PEG-HA implants were able to maintain near their original volume for up to 491 days, whereas control HA injections were completely resorbed. Notably, these HA-based materials were partially reversible with the addition of the enzyme hyaluronidase. To translate this material to the clinic, Hillel et al. then tested the PEG-HA composites in humans. The polymer was injected into the intradermal space in the abdomen of three patients scheduled to undergo abdominoplasty surgery. Similar to the rodent studies, the PEG-HA material persisted for 12 weeks, whereas the control HA injections lost their shape. An inflammatory response was observed surrounding the injections. It is clear that this new photo-friendly polymer and transdermal crosslinking method will be clinically useful for soft tissue reconstruction—perhaps even encouraging more people to put their best faces forward in the spotlight. Soft tissue reconstruction often requires multiple surgical procedures that can result in scars and disfiguration. Facial soft tissue reconstruction represents a clinical challenge because even subtle deformities can severely affect an individual’s social and psychological function. We therefore developed a biosynthetic soft tissue replacement composed of poly(ethylene glycol) (PEG) and hyaluronic acid (HA) that can be injected and photocrosslinked in situ with transdermal light exposure. Modulating the ratio of synthetic to biological polymer allowed us to tune implant elasticity and volume persistence. In a small-animal model, implanted photocrosslinked PEG-HA showed a dose-dependent relationship between increasing PEG concentration and enhanced implant volume persistence. In direct comparison with commercial HA injections, the PEG-HA implants maintained significantly greater average volumes and heights. Reversibility of the implant volume was achieved with hyaluronidase injection. Pilot clinical testing in human patients confirmed the feasibility of the transdermal photocrosslinking approach for implantation in abdomen soft tissue, although an inflammatory response was observed surrounding some of the materials.

Comparison of 3 techniques of fat grafting and cell-supplemented lipotransfer in athymic rats: a pilot study.

BACKGROUND Given the wide application of autologous fat grafting, a new emphasis on fat processing techniques has emerged in an effort to limit unpredictable degrees of resorption often seen with this procedure. With the growing interest in regenerative medicine, approaches to supplement fat grafts with adipose-derived stem cells are evolving in hopes of promoting vascularization and neoadipogenesis. OBJECTIVE The authors evaluated the outcomes of the most common processing techniques for fat grafting--decantation, washing, high-speed centrifugation--and stromal vascular cell-supplemented lipotransfer to determine which method yields a higher percentage of retention and better quality graft. METHODS A total of 32 subcutaneous injections of processed human lipoaspirate were carried out in 8 athymic rats. Each animal received all 4 processing conditions, with end points at 4, 8, and 12 weeks postinjection. Evaluation of graft survival included serial measurements of volume retention and histologic analysis. RESULTS At 12 weeks postinjection, cell-supplemented and centrifuged grafts showed the most consistent volume maintenance. Based on histologic analysis, cell-supplemented and washed grafts had higher scores of viability and vascularity, with the former presenting the least cystic necrosis and calcification as well as minimal inflammation. CONCLUSIONS Cell-supplemented lipotransfer had optimal outcomes for graft retention, viability, and vascularity, while washing resulted in high viability with a less intensive process. High-speed centrifugation resulted in consistent volume retention but lower viability. Each of these approaches is ideal under different circumstances and contributes to the versatility and reliability of fat grafting.

Application of a Collagen-Based Membrane and Chondroitin Sulfate-Based Hydrogel Adhesive for the Potential Repair of Severe Ocular Surface Injuries

This study was performed to evaluate the potential of a chondroitin sulfate-polyethylene glycol (CS-PEG) adhesive and collagen-based membrane (collagen vitrigel, CV) combination as a method to treat penetrating ocular injuries on the battlefield and to improve this method with two technologies: an antibiotic releasing CS-PEG adhesive and a corneal shaped CV. Burst testing using porcine cadaveric eyes, high-performance liquid chromatography, the Kirby-Bauer bacterial inhibition test, and CV implantations on the live and cadaveric rabbit eyes were performed. The ocular burst test showed CS-PEG adhesive could successfully repair 5-mm to 6-mm length wounds in the corneal and corneoscleral regions but would require CS-PEG + CV to treat larger wounds similar to those seen on the battlefield. In addition, high performance liquid chromatography and the Kirby-Bauer bacterial inhibition test presented evidence suggesting the vancomycin incorporated CS-PEG could inhibit Staphylococcus infection for 9 days. Furthermore, the curved CV showed an advantage by matching the corneal contour without any wrinkle formation. Although this pilot study showed a limited range of possible applications, we demonstrated that the combination of CS-PEG adhesive + CV is a promising method and the 2 technologies improve their applicability to the special demands of the battlefield.