Azhar Zam

Advances in bone marrow stem cell therapy for retinal dysfunction

ABSTRACT The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age‐related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow‐derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non‐cellular alternatives using extracellular vesicles, and in vivo high‐resolution retinal imaging to detect cellular changes in the retina following cell therapy. HIGHLIGHTSThere are various types of bone marrow stem cells.These stem cells have paracrine trophic effects on damaged tissue.The stem cells are useful for a variety of retinal conditions.This investigational therapy is being explored in clinical trials.

Enabling Minimal Invasive Palpation in Flexible Robotic Endoscopes

In open surgery, palpation allows surgeons to haptically examine the patient’s tissue with their fingers. Hereby, palpation relates the pose of the surgeon’s finger inside the wound and the finger’s indentation into the tissue to the experienced forces in all directions. In this way, the surgeon is able to experience differences in tissue stiffness. Despite being a well-recognized standard procedure in open surgery, palpation has so far been unavailable for Minimally Invasive Surgery (MIS). Thus, surgeons can only rely on endoscope vision. To overcome this drawback, we aim to restore haptic feedback and thus palpation in MIS.

Performance of Er:YAG laser ablation of hard bone under different irrigation water cooling conditions

The biological applicability of the Erbium-doped Yttrium Aluminum Garnet (Er:YAG) laser in surgical processes is so far limited to hard dental tissues. Using the Er:YAG laser for bone ablation is being studied since it has shown good performance for ablating dental hard tissues at the wavelength 2.94 μm, which coincides with the absorption peak of water, one of the main components of hard tissue, like teeth and bone. To obtain a decent performance of the laser in the cutting process, we aim at examining the influence of sequenced water jet irrigation on both, the ablation rate and the prevention of carbonization while performing laser ablation of bone with fixed laser parameters. An Er:YAG laser at 2.94 μm wavelength, 940 mJ energy per pulse, 400 μs pulse width, and 10 Hz repetition rate is used for the ablation of a porcine femur bone under different pulsed water jet irrigation conditions. We used micro-computed tomography (micro-CT) scans to determine the geometry of the ablated areas. In addition, scanning electron microscopy (SEM) is used for qualitative observations for the presence of carbonization and micro-fractures on the ablated surfaces. We evaluate the performance of the laser ablation process for the different water jet conditions in terms of the ablation rate, quantified by the ablated volume per second and the ablation efficiency, calculated as the ablated volume per pulse energy. We provide an optimized system for laser ablation which delivers the appropriate amount of water to the bone and consequently, the bone is ablated in the most efficient way possible without carbonization.

Plasma plume expansion dynamics in nanosecond Nd:YAG laserosteotome

In minimal invasive laser osteotomy precise information about the ablation process can be obtained with LIBS in order to avoid carbonization, or cutting of wrong types of tissue. Therefore, the collecting fiber for LIBS needs to be optimally placed in narrow cavities in the endoscope. To determine this optimal placement, the plasma plume expansion dynamics in ablation of bone tissue by the second harmonic of a nanosecond Nd:YAG laser at 532 nm has been studied. The laserinduced plasma plume was monitored in different time delays, from one nanosecond up to one hundred microseconds. Measurements were performed using high-speed gated illumination imaging. The expansion features were studied using illumination of the overall visible emission by using a gated intensified charged coupled device (ICCD). The camera was capable of having a minimum gate width (Optical FWHM) of 3 ns and the timing resolution (minimum temporal shift of the gate) of 10 ps. The imaging data were used to generate position–time data of the luminous plasma-front. Moreover, the velocity of the plasma plume expansion was studied based on the time-resolved intensity data. By knowing the plasma plume profile over time, the optimum position (axial distance from the laser spot) of the collecting fiber and optimal time delay (to have the best signal to noise ratio) in spatial-resolved and time-resolved laser-induced breakdown spectroscopy (LIBS) can be determined. Additionally, the function of plasma plume expansion could be used to study the shock wave of the plasma plume.

Differentiation of femur bone from surrounding soft tissue using laser-induced breakdown spectroscopy as a feedback system for smart laserosteotomy

Although laserosteotomes have become generally accepted devices in surgical applications, they still suffer from a lack of information about the type of tissue currently being ablated; as a result, critical structures of the body under or near the focal spot of the laser beam are prone to inadvertent ablation. The lack of information about the properties of the ablated tissue can be solved by connecting the laserosteotome to an optical detection setup which can differentiate various types of tissues, especially bone from connective soft tissues. This study examines the applicability of laser-induced breakdown spectroscopy (LIBS) as a potential technique to differentiate bone from surrounding soft tissue (fat and muscle). In this experiment, fresh porcine femur bone, muscle, and fat were used as hard and soft tissue samples. The beam of a nanosecond frequency–doubled Nd:YAG laser was used to ablate the tissue samples and generate the plasma. The plasma light emitted from the ablated spot, which corresponds to the recombination spectra of ionized atoms and molecules, was gathered with a collection optic (including a reflective light collector and a fiber optic) and sent to an Echelle spectrometer for resolving the atomic composition of the ablated sample. Afterwards, Discriminant Function Analysis (DFA) based on the ratio of the intensity of selected peak pairs was performed to classify three sample groups (bone, muscle, and fat). Lastly, the sensitivity, specificity, and accuracy of the proposed method were calculated. Sensitivity and specificity of 100 % and 99 % were achieved, respectively, to differentiate bone from surrounding soft tissue.

Comparison of acoustic shock waves generated by micro and nanosecond lasers for a smart laser surgery system

Characterization of acoustic shock wave will guarantee efficient tissue differentiation as feedback to reduce the probability of undesirable damaging (i.e. cutting) of tissues in laser surgery applications. We ablated hard (bone) and soft (muscle) tissues using a nanosecond pulsed Nd:YAG laser at 532 nm and a microsecond pulsed Er:YAG laser at 2.94 μm. When the intense short ns-pulsed laser is applied to material, the energy gain causes locally a plasma at the ablated spot that expands and propagates as an acoustic shock wave with a rarefaction wave behind the shock front. However, when using a μs-pulsed Er:YAG laser for material ablation, the acoustic shock wave is generated during the explosion of the ablated material. We measured and compared the emitted acoustic shock wave generated by a ns-pulsed Nd:YAG laser and a μs-pulsed Er:YAG laser measured by a calibrated microphone. As the acoustic shock wave attenuates as it propagates through air, the distance between ablation spots and a calibrated microphone was at 5 cm. We present the measurements on the propagation characteristics of the laser generated acoustic shock wave by measuring the arrival time-of-flight with a calibrated microphone and the energy-dependent evolution of acoustic parameters such as peak-topeak pressure, the ratio of the peak-to-peak pressures for the laser induced breakdown in air, the ablated muscle and the bone, and the spectral energy.

Effect of cooling water on ablation in Er:YAG laserosteotome of hard bone

The aim of this paper is to examine the effect of pig bone immersion in different levels of cooling water during laser ablation with a Er:YAG laser. The laser worked at 2940 nm wavelength and 10 Hz repetition rate in microseconds pulse duration regime. The bone was immersed in different levels of cooling water in a sample container for preventing carbonization. The bone samples were ablated with fixed deposited energy to investigate at which water level Er:YAG lasers start ablating bone through a layer of water. Results showed that the maximum level of water that laser can pass through to start the ablation nonlinearly depends on pulse energy.

Effect of laser pulse duration on ablation efficiency of hard bone in microseconds regime

The aim of the present study is to investigate the effect of laser pulse duration on ablation efficiency of hard bones. The bones were ablated using a microsecond pulsed Er-YAG laser. The laser wavelength was 2.94 μm and the repetition rate was 10Hz. Three samples of porcine femur were used and several areas were ablated with a fixed pulse energy of 280mJ and different pulse durations. The ablation procedure was applied during five seconds for all the experiments, therefore, the same amount of energy (14 J) was deposited in each trial. The ablation efficiency was determined by measuring the ablated volume per second for each experiment.

Characterization of ablated porcine bone and muscle using laser-induced acoustic wave method for tissue differentiation

A high power pulsed laser with millisecond pulse was used to interact with a bone and muscle of porcine, initiating an acoustic wave. We start to describe principle of laser ablation follows by the acoustic wave generation. Then, we present the characterization of these wave features for laser surgery applications.