Michael Taylor

Sylvatica Bio & Carnegie Mellon University · Mechanical Engineering

Introduction Transplantation of kidneys from expanded criteria donors (ECD), including after circulatory death (DCD), is associated with a higher risk of adverse events compared to kidneys from standard criteria donors. In previous studies, improvements in renal transplant outcomes have been seen when kidneys were perfused with gaseous oxygen durin...

Introduction: The current liver organ shortage has pushed the field of transplantation to develop new methods to prolong the preservation time of livers from the current clinical standard of static cold storage. Our approach, termed partial freezing, aims to induce a thermodynamically stable frozen state at high subzero storage temperatures (−10°C...

The current liver organ shortage has pushed the field of liver transplantation to develop new methods to prolong the preservation time of livers from the current clinical standard of static cold storage. Our approach, termed partial freezing, aims to induce a thermodynamically stable frozen state at deeper storage temperatures (–10°C to –15°C) than...

Purpose Herein, we evaluate the use of MRI as a tool for assessing iron oxide nanoparticle (IONP) distribution within IONP perfused organs and vascularized composite allografts (VCAs) (i.e., hindlimbs) prepared for cryopreservation. Methods Magnetic resonance imaging was performed on room‐temperature organs and VCAs perfused with IONPs and were as...

In this concept article we outline a variety of new approaches that have been conceived to address some of the remaining challenges for developing improved methods of biopreservation. This recognizes a true renaissance and variety of complimentary, high potential approaches leveraging nature inspiration, nanotechnology, thermodynamics of pressure a...

Ice-free vitreous cryopreservation (vitrification) is regarded as the principal method for avoiding ice crystallization damage in cryopreserved tissues and organs. We previously established the fundamental thermodynamics of isochoric (constant volume) systems for cryopreservation, and now extend this novel approach to vitrification in an isochoric...

Vitrification tendency and stability of the amorphous state were analyzed by means of differential scanning calorimetry (DSC) for the vitrification solution DP6, with and without additional solutes to enhance ice suppression. This study is a part of an ongoing research effort to characterize the thermophysical and mechanical properties of DP6 and i...

The ability to replace organs and tissues on-demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery and a variety of rapidly advancing a...

The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing...

Diabetes is a major health problem worldwide, and there is substantial interest in developing xenogeneic islet transplantation as a potential treatment. The potential to relieve the demand on an inadequate supply of human pancreata is dependent upon the efficiency of techniques for isolating and culturing islets from the source pancreata. Porcine i...

Insulin-dependent diabetes mellitus is one of the leading causes of death world wide. Donor-derived pancreas and islet of Langerhans transplantation are potential cures, however, postmortem ischemia impacts islet quality. The murine βt3 cell line was used as a model to study apoptosis after hypothermic storage by comparing Unisol™ with Belzer's mac...

Cell-based therapies, which all involve processes for procurement and reimplantation of living cells, currently rely upon expensive, inconsistent, and even toxic enzyme digestion processes. A prime example is the preparation of isolated pancreatic islets for the treatment of type 1 diabetes by transplantation. To avoid the inherent pitfalls of thes...

This study provides thermal expansion data for blood vessels permeated with the cryoprotective cocktail DP6, when combined with selected synthetic ice modulators (SIMs): 12% polyethylene glycol 400, 6% 1,3-cyclohexanediol, and 6% 2,3-butanediol. The general classification of SIMs includes molecules that modulate ice nucleation and growth, or posses...

In recent years the role of hypothermia as the bedrock for organ preservation techniques, has received renewed attention due to its importance in the procurement, storage and resuscitation of less-than-optimal donor organs. Clinical kidney and liver transplantation has evolved from an experimental procedure 50 years ago to the current treatment of...

The objective of the current study is to develop a new cryomacroscope prototype for the study of vitrification in large-size specimens. The unique contribution in the current study is in developing a cryomacroscope setup as an add-on device to a commercial controlled-rate cooler and in demonstration of physical events in cryoprotective cocktails co...

In recent years the role of hypothermia as the bedrock upon which techniques of organ preservation are based, has received renewed attention due to its importance in the procurement, storage and resuscitation of less-than-optimal donor organs. Clinical kidney and liver transplantation has evolved from an experimental procedure 50 years ago to the c...

An organ perfusion apparatus and method monitor, sustain and/or restore viability of organs and preserve organs for storage and/or transport. Other apparatus include an organ transporter, an organ cassette and an organ diagnostic device. The method includes perfusing the organ at hypothermic and/or normothermic temperatures. The methods further inc...

Porcine islet xenotransplantation is considered a potential cell-based therapy for type 1 diabetes. It is currently being evaluated in diabetic nonhuman primates (NHP) to assess safety and efficacy of the islet product. However, due to a variety of distinct differences between the respective species, including the insulin secretory characteristics...

Insulin-dependent diabetes mellitus is one of the leading causes of death world-wide. Donor-derived pancreas and Islet of Langerhans transplantation are potential cures; however, postmortem ischemia impacts islet quality. The murine βt3 cell line was employed as a model to study cell viability and proliferation after hypothermic storage by comparin...

This study explores physical effects associated with the application of cryopreservation via vitrification using a class of compounds which are defined here as synthetic ice modulators (SIMs). The general classification of SIMs includes molecules that modulate ice nucleation and growth, or possess properties of stabilizing the amorphous state, by v...

It has been recently reported that adding various synthetic ice blockers (SIBs) to the cryoprotective agent (CPA) cocktail DP6 decreased the onset of crystallization, which is a favorable condition for cryopreservation - the preservation of tissues at very low temperatures. DP6 is a CPA cocktail which has drawn significant attention in the cryobiol...

Improved preservation techniques have the potential to improve transplant outcomes by better maintaining donor organ quality and by making more organs available for allotransplantation. Persufflation, (PSF, gaseous oxygen perfusion) is potentially one such technique that has been studied for over a century in a variety of tissues, but has yet to ga...

CELL TRANSPLANTATION (PART B) - CELL MEDICINE

The demand for high-quality islets for transplantation in type I diabetics will increase as the current clinical trials transition into standard of care. The mode of preservation of donor pancreata is critical to this mission since islets are very sensitive to ischemic injury. Hypothermic perfusion preservation (HPP) is being investigated for exten...

A critical component of treating type I diabetes by transplantation is the availability of sufficient high-quality islets. Currently, islets can be obtained only by reliance on an expensive, inconsistent, and toxic enzyme digestion process. As an alternative, we hypothesize that cryobiologic techniques can be used for differential freeze destructio...

Magnetic isolation is a promising method for separating and concentrating pancreatic islets of Langerhans for transplantation in Type 1 diabetes patients. We are developing a continuous magnetic islet sorter to overcome the restrictions of current purification methods that result in limited yield and viability. In Quadrupole Magnetic Sorting (QMS)...

Procurement and preservation of pancreata is important for both segmental gland transplantation and islet isolation as a prelude to islet transplantation as a potentially new option for the treatment of Type I diabetes mellitus. The methods described here focus on the latter application and apply the LifePort® kidney platform transporter to prolong...

This review focuses on the application of hypothermic perfusion technology as a topic of current interest with the potential to have a salutary impact on the mounting clinical challenges to improve the quantity and quality of donor organs and the outcome of transplantation. The ex vivo perfusion of donor organs on a machine prior to transplant, as...

Pancreas procurement for islet isolation and transplantation is limited by concerns for the detrimental effects of postmortem ischemia. Hypothermic machine perfusion (HMP) preservation technology has had a major impact in circumventing ischemic injury in clinical kidney transplantation and is applied here to the preservation and procurement of viab...

The pathophysiology of hypothermia (cold stress) on homeothermic animals, including humans, can be considered at both the systemic (whole body) and cellular level. This article describes the general physiological responses to hypothermia before concluding with an outline of events at the cellular level. Where appropriate, reference is also made to...

Transplantation of pancreatic islets for the treatment of diabetes mellitus is widely anticipated to eventually provide a cure once a means for preventing rejection is found without reliance upon global immunosuppression. Long-term storage of islets is crucial for the organization of transplantation, islet banking, tissue matching, organ sharing, i...

Aseptic loosening in the acetabular component is the most prevalent cause of failure in cemented total hip arthroplasty (THA) [1]. There is clinical evidence of high polyethylene cup wear accompanying acetabular aseptic loosening [2]. One such study discriminated between cups experiencing low and high wear, showing the revision rate in the high-wea...

Cryopreservation is a well-established technique for long-term storage of viable cells and tissues. However, in recent years, application of established cryobiological principles to the preservation of multicellular tissues and organs has demanded considerable attention to ways of circumventing the deleterious effects of ice and thermal stresses in...

Procurement of donor pancreata for islet isolation and transplantation is not yet widely practiced due to concerns about the impact of postmortem ischemia on functional islet yields. Perfusion/preservation technology may help to circumvent ischemic injury as applied in this study of porcine pancreata prior to islet isolation. Pancreata harvested fr...

Clinical applications of hypothermia range from ex vivo storage of cells, tissues and organs for transplantation or cell-based therapies to in vivo protection of a patient during complex surgeries that might entail circulatory and/or cardiac arrest. The intent of this brief review is to outline the essential principles of hypothermia applied in the...

The purpose of this study was to compare vitrified small diameter venous arterial bypass graft explants with fresh graft controls using quantitative morphometries and smooth muscle physiology. Fresh and vitrified reversed ipsilateral external jugular veins were used as autologous common carotid interposition bypass grafts on the right side in New Z...

This study documents renal biochemistry during hypothermic machine perfusion of kidneys. It is intended to demonstrate that a comprehensive evaluation of organ viability during ex-vivo preservation is needed to increase the number of organs available for transplantation and to reduce the current renal discard rate. Porcine kidneys were hypothermica...

In recent years, ice-free cryopreservation by vitrification has been demonstrated to provide superior preservation of tissues compared with conventional freezing methods. To date, this has been accomplished almost exclusively for small model systems, whereas cryopreservation of large tissue samples-of a clinically useful size-continues to be hamper...

To meet the current clinical organ demand, efficient preservation methods and solutions are needed to increase the number of viable kidneys for transplantation. In the present study, the influence of perfusion solution buffering strength on renal pH dynamics and regulation mechanisms during kidney ex vivo preservation was determined. Porcine kidney...

A new imaging device, termed a "cryomacroscope", was used to observe macrofractures in the cryoprotectant cocktails DP6 and VS55. Details of the design and construction of the cryomacroscope were presented in Part I of this report, which focused on describing the apparatus and observations of crystallization. Part I and the current paper (Part II)...

A new imaging device, termed a "cryomacroscope", is presented in this report. This device is designed to assist in exploring thermal and mechanical effects associated with large-scale vitrification and crystallization, with the current setup aimed at the range of 50 μm to 2 cm. The cryomacroscope is not intended as a substitute for the cryomicrosco...

Despite significant advances, some critical issues remain for the long-term storage of an engineered pancreas. In this study we employed a tissue engineered pancreatic substitute model-insulin-secreting betaTC3 cells entrapped in calcium alginate/poly-L-lysine/alginate beads-to demonstrate that a prototype vitrification method can prevent ice forma...

Hypothermic machine perfusion (HMP) has a potential to relieve the current donor liver crisis by providing an improved and extended preservation method. This study examined the effect of HMP on hepatocellular functions, using a prototype liver transporter capable of preserving livers for 24 hours. Livers obtained from adult farm pigs (28 to 32 kg b...

The success of endovascular techniques such as balloon angioplasty and stenting in the treatment of atherosclerotic vascular disease has been limited by an aggressive proliferative response leading to neointimal hyperplasia and re-stenosis. A new endovascular therapy combining cold treatment with balloon dilation has been proposed to prevent arteri...

Background: Autologous veins are commonly stored briefly prior to implantation for vascular reconstructive surgery. Several factors have previously been demonstrated to influence the quality of vein grafts during vein preparation for arterial bypass procedures, including the dissection technique employed, the solution used, the distension pressure,...

Evaluation methods are required for non-heart-beating donor (NHBD) kidneys to ensure the success of transplantation. In this study, the microdialysis technique was employed for the ex-vivo assessment of hypothermically preserved NHBD kidney function. Microdialysis probes were placed in the renal cortex of 2 h warm ischaemic porcine kidneys to monit...

The growing need for improved methods of viable tissue cryopreservation has stimulated debate regarding the relative merits of traditional freezing methods versus ice-free vitrification methods. Articular cartilage has proved refractory to satisfactory cryopreservation using conventional freezing methods. Therefore, full-thickness rabbit femoral he...

Articular cartilage has proved refractory to satisfactory cryopreservation using conventional freezing methods. Therefore, an ice-free cryopreservation method by vitrification was tested. Osteochondral plugs from New Zealand White rabbits were preserved using either a freezing method or an ice-free vitrification method of cryopreservation. Preserve...

The design of new solutions for the universal preservation of tissues is a quest that would facilitate multiple-organ harvesting from organ donors since current preservation solutions do not provide optimum preservation for all organs. In contrast, a new approach to bloodless surgery using hypothermic blood substitution (HBS) to protect the whole b...

Description Written by an international group of industry experts, regulators, and academics, this new ASTM publication provides the latest data on tissue engineering and the standards available for manufacturing TEMPs. Twenty-three peer-reviewed papers cover This new publication serves as a valuable resource for regulators, manufacturers, supplier...