Boonsin Buranapanitkit

Development of approaches to improve the healing following muscle contusion

Muscle injuries are a challenging problem in traumatology, and the most frequent occurrence in sports medicine. Muscle contusions are among the most common muscle injuries. Although this injury is capable of healing, an incomplete functional recovery often occurs, depending on the severity of the blunt trauma. We have developed an animal model of muscle contusion in mice (high energy blunt trauma) and characterized the muscles ability to heal following this injury using histology and immunohistochemistry to determine the level of muscle regeneration and the development of scar tissue. We have observed a massive muscle regeneration occurring in the first 2 wk postinjury that is subsequently followed by the development of muscle fibrosis. Based on these observations, we propose that the enhancement of muscle growth and regeneration, as well as the prevention of fibrotic development, could be used as approach(es) to improve the healing of muscle injuries. In fact, we have identified three growth factors (bFGF, IGF-1, and NGF) capable of enhancing myoblast proliferation and differentiation in vitro and improving the healing of the injured muscle in vivo. Furthermore, the ability of adenovirus to mediate direct and ex vivo gene transfer of beta-galactosidase into the injured site opens possibilities of delivering an efficient and persistent expression of these growth factors in the injured muscle. These studies should help in the development of strategies to promote efficient muscle healing with complete functional recovery following muscle contusion.

Biologic intervention in muscle healing and regeneration

Muscle injuries are a challenging problem in traumatology and the most frequently occurring injuries in sports medicine. Even though muscles retain their ability to regenerate after injury, the healing process of muscles after such injuries has been found to be slow and often leads to an incomplete muscle recovery. In an attempt to develop approaches to improve muscle healing after injury, the authors have developed reproducible injury models for muscle contusion, strain, and laceration. The authors show that muscle regeneration occurs after those injuries, but the development of scar tissue greatly limits the natural healing process. It is likely that an enhancement of muscle growth and regeneration can be used to improve muscle healing after injuries. The authors have then identified growth factors that enhance myoblast proliferation and differentiation in vitro and muscle regeneration in the injured muscles, which improves muscle healing after injuries. Furthermore, different gene transfer systems, including cell and gene therapy, have been found successful in delivering genes into injured muscles and may open new opportunities to deliver growth factors and improve muscle healing after lacerations, contusions, and strains.

Biocompatability of hydroxyapatite composite as a local drug delivery system

Purpose. To investigate the biocompatibility of hydroxyapatite composite (hydroxyapatite, plaster of Paris, and chitosan) impregnated with gentamicin, fosfomycin, imipenem, or amphotericin B. Methods. The interactions of the extract from each drug against osteoblast were tested using the methylthiotetrazole test. Results. Extracts from all drugs showed good biocompatibility at concentrations varying from 10 μg/ml to 1000 μg/ml. Imipenem and amphotericin B at a concentration of 1000 μg/ml had a significantly higher percentage of cell viability than the control group. No morphological change of osteoblast was observed in all drug tests at any concentrations. Conclusion. The hydroxyapatite composite had a good biocompatibility for carrying gentamicin, fosfomycin, imipenem, or amphotericin B.

The efficacy of hydroxyapatite composite impregnated with amphotericin B.

We investigated the efficacy of local biodegradable composites composed of hydroxyapatite-plaster of paris and either chitosan or alginate binder impregnated with amphotericin B. Antifungal activity was tested for Candida albicans using a modified disc diffusion technique for 6 weeks and compared with similarly impregnated polymethylmethacrylate. The physicochemical properties of each preparation were evaluated using scanning electron microscopy and Fourier transform infrared spectroscopy. The antifungal activity of amphotericin B eluted from the hydroxyapatite composites was significantly greater than the polymethylmethacrylate after 7 days. The hydroxyapatite composites and the polymethylmethacrylate system sustained their antifungal activity for at least 1 month. However, after 5 weeks, the antifungal activities of the polymethylmethacrylate systems rapidly lessened, while the hydroxyapatite composites sustained their activities at a much higher level. We found no difference in antifungal activity between the hydroxyapatite composite using either the chitosan or alginate binder. Scanning electron microscopy and Fourier transform infrared spectroscopy revealed the drug release profile. The hydroxyapatite composites impregnated with amphotericin B showed superior antifungal efficacy over those loaded in polymethylmethacrylate in an in vitro study, but additional in vivo research is needed to confirm this result.

CLINICAL PREDICTORS FOR OUTCOME OF TREATMENT OF LUMBAR HERNIATED NUCLEUS PALPOSUS

Herniated nucleus palposus is a common and important cause of low back pain. Despite over 90% of the patients responding to conservative treatment, some patients still need operation. This study aimed to analyze the clinical predictors for the outcome of conservative treatment in herniated nucleus palposus. Two hundred and fifty-one patients who were diagnosed as lumbar herniated nucleus palposus and admitted to Prince of Songkla University during the period of 1995–2000 were included in the study. Patients who had absolute indications for surgery or had previous back surgery were excluded. Data were collected on demographic characteristics (age, sex, occupation, level of study, marital status), patient symptoms (including duration, characteristic and severity of pain) and result of physical examination (including result of straight leg raising test (SLRT), cross SLRT, motor power, sensory deficit and reflex). The mean age of the patients was 38 years and the mean duration of pain was 4.1 months. Eighty percent of the patients had positive SLRT and abnormal neurological function was found in 73%. One hundred and eighty-six patients underwent surgery owing to failure of conservative treatment. From multivariate logistic analysis, five independent factors affecting failure of conservative treatment of herniated nucleus palposus were pain intensity, duration of symptoms, positive cross SLRT, grade of muscle power and number of dermatome deficit. When constructing the parameters into a scoring system, we found that if the patient had a score less than 45, 80% of them respond to conservative treatment, in contrast to those who scored more than 65, the probability of conservative failure was 80%. This study implies that clinical predictors can be used for determining probability of conservative failure in herniated nucleus palposus.