Comparing an optical parametric oscillator (OPO) as a viable alternative for mid-infrared tissue ablation with a free electron laser (FEL).

Beneficial medical laser ablation removes material efficiently with minimal collateral damage. A Mark-III free electron laser (FEL), at a wavelength of 6.45 µm has demonstrated minimal damage and high ablation yield in ocular and neural tissues. While this wavelength has shown promise for surgical applications, further advances are limited by the high overhead for FEL use. Alternative mid-infrared sources are needed for further development. We compared the FEL with a 5-µs pulse duration with a Q-switched ZGP-OPO with a 100-ns pulse duration at mid-infrared wavelengths. There were no differences in the ablation threshold of water and mouse dermis with these two sources in spite of the difference in their pulse structures. There was a significant difference in crater depth between the ZGP:OPO and the FEL. At 6.1 µm, the OPO craters are eight times the depth of the FEL craters. The OPO craters at 6.45 and 6.73 µm were six and five times the depth of the FEL craters, respectively. Bright-field (pump-probe) images showed the classic ablation mechanism from formation of a plume through collapse and recoil. The crater formation, ejection, and collapse phases occurred on a faster time-scale with the OPO than with the FEL. This research showed that a ZGP-OPO laser could be a viable alternative to FEL for clinical applications.

Laser-induced disruption of systemically administered liposomes for targeted drug delivery.

Liposomal formulations of drugs have been shown to enhance drug efficacy by prolonging circulation time, increasing local concentration and reducing off-target effects. Controlled release from these formulations would increase their utility, and hyperthermia has been explored as a stimulus for targeted delivery of encapsulated drugs. Use of lasers as a thermal source could provide improved control over the release of the drug from the liposomes with minimal collateral tissue damage. Appropriate methods for assessing local release after systemic delivery would aid in testing and development of better formulations. We use in vivo bioluminescence imaging to investigate the spatiotemporal distribution of luciferin, used as a model small molecule, and demonstrate laser-induced release from liposomes in animal models after systemic delivery. These liposomes were tested for luciferin release between 37 and 45 degrees C in PBS and serum using bioluminescence measurements. In vivo studies were performed on transgenic reporter mice that express luciferase constitutively throughout the body, thus providing a noninvasive readout for controlled release following systemic delivery. An Nd:YLF laser was used (527 nm) to heat tissues and induce rupture of the intravenously delivered liposomes in target tissues. These data demonstrate laser-mediated control of small molecule delivery using thermally sensitive liposomal formulations.

Accelerated bone repair after plasma laser corticotomies.

OBJECTIVE: To reveal, on a cellular and molecular level, how skeletal regeneration of a corticotomy is enhanced when using laser-plasma mediated ablation compared with conventional mechanical tissue removal. SUMMARY BACKGROUND DATA: Osteotomies are well-known for their most detrimental side effect: thermal damage. This thermal and mechanical trauma to adjacent bone tissue can result in the untoward consequences of cell death and eventually in a delay in healing. METHODS: Murine tibial corticotomies were performed using a conventional saw and a Ti:Sapphire plasma-generated laser that removes tissue with minimal thermal damage. Our analyses began 24 hours after injury and proceeded to postsurgical day 6. We investigated aspects of wound repair ranging from vascularization, inflammation, cell proliferation, differentiation, and bone remodeling. RESULTS: Histology of mouse corticotomy sites uncovered a significant difference in the onset of bone healing; whereas laser corticotomies showed abundant bone matrix deposition at postsurgical day 6, saw corticotomies only exhibited undifferentiated tissue. Our analyses uncovered that cutting bone with a saw caused denaturation of the collagen matrix due to thermal effects. This denatured collagen represented an unfavorable scaffold for subsequent osteoblast attachment, which in turn impeded deposition of a new bony matrix. The matrix degradation induced a prolonged inflammatory reaction at the cut edge to create a surface favorable for osteochondroprogenitor cell attachment. Laser corticotomies were absent of collagen denaturation, therefore osteochondroprogenitor cell attachment was enabled shortly after surgery. CONCLUSION: In summary, these data demonstrate that corticotomies performed with Ti:Sapphire lasers are associated with a reduced initial inflammatory response at the injury site leading to accelerated osteochondroprogenitor cell migration, attachment, differentiation, and eventually matrix deposition.