Company
Portfolio Data
Back to Company Search21st Century Medicine, Inc.
UEI: NG8VBJR2LKK3
Number of Employees: 22
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
SBIR/STTR Involvement
Year of first award: 2002
8
Phase I Awards
2
Phase II Awards
25%
Conversion Rate
$1,638,899
Phase I Dollars
$2,388,786
Phase II Dollars
$4,027,685
Total Awarded
Awards
Whole Ovary Vitrification for Fertility Preservation
Amount: $1,553,682 Topic: NICHD
PROJECT SUMMARY The long-term goal of this proposal is to develop a safe, effective and user-friendly vitrification system for cryopreservation of whole human ovaries. In the U.S., over 140,000 girls and women age 0-49 are diagnosed with cancer annually. While improved diagnosis and treatment have led to increased survival rates (75% in premenopausal and 85% in childhood cancer patients), devastating side effects of cancer therapies include premature ovarian failure, infertility and menopause-related health risks. While cryopreservation of embryos and oocytes are effective, ovarian cortex and whole ovary cryopreservation is the only option for future fertility in prepubertal patients and those who require immediate cancer treatment. Cryopreservation of whole ovaries, compared to ovarian tissue, has added advantages of 1) preserving all classes of follicles, which can be used for in vitro maturation, 2) longer graft lifespan, and 3) faster recovery supported by existing blood vessels after transplantation with vascular anastomosis. However, current methods for whole ovary cryopreservation are suboptimal and there is no technology designed for cryopreserving human ovaries, despite it being the best choice for prepubertal cancer patients for future fertility and intact endocrine function for decades without the help of exogenous hormones. The proposed research is part of 21st Century Medicine’s more general program of developing superior organ cryopreservation systems, including cryoprotective agent (CPA) solutions, perfusion apparatus (hardware and software) for CPA loading and unloading, and liquid nitrogen storage units. This Phase II will help us initiate our effort in achieving our ultimate goal as an organ banking company. Our company has successfully demonstrated functional preservation of vitrified rabbit kidneys after transplantation. In this SBIR Phase II study, we will validate and continue improving our success thus far in whole ovary vitrification using large animal models of ovary transplantation in pigs and sheep (sheep has an established ovary transplant procedure and their ovarian structure is closer to the human than the pig). We will also develop a nonhuman primate preclinical model for ovary transplantation as well as characterize the cryogenic properties of monkey ovaries. Furthermore, we will finalize the Ovary Perfusion Device and develop a closed system for storing individual cryopreserved ovaries for eventual clinical use. The resultant technology of this Phase II project will be the first perfusion unit designed for the human ovary and can simultaneously control temperature, pressure, flow rate and CPA concentration with a build-in feedback mechanism to maintain constant pressure during perfusion. Upon successful completion of Phase II, we will submit a Phase IIb application to include fertility trials using the nonhuman primate model, human tissue xenografting experiments, and finalizing strategies for commercialization. This novel system will offer new hope to the thousands of cancer survivors and the impact could be significant and sustained.PROJECT NARRATIVE One devastating side effect of cancer treatment is premature ovarian failure which can lead to infertility and long term health risks associated with menopause. Compared to existing fertility preservation methods (embryo, oocyte and ovarian tissue cryopreservation), whole ovary cryopreservation offers complete recovery of ovarian function (endocrine and fertility), which is important for young, especially prepubertal, cancer patients. Currently, technology for cryopreservation of whole human ovaries does not exist; therefore, the overall objective for this SBIR project is to develop a safe, effective and user-friendly cryopreservation system for human ovaries.
Tagged as:
SBIR
Phase II
2020
HHS
NIH
Development of Novel Storage Method for Highly Viable and Well-Characterized Vitrified Human Islets
Amount: $296,095 Topic: 200
Project Summary Abstract The ultimate objective of the proposed research is to enable the long term banking of curative doses of human pancreatic islets for the reversal of typediabetes and the amelioration of typediabetes and to understand storage injury near the glass transition temperatureTGto enable a new type of long term storage to be developedBanking should reduce or prevent the deterioration of islets prior to usefacilitate tolerance inductionenable delayed islet transplantation following transplantation of a kidney from the same donor weeks earlierand have many other benefitsWe have already demonstratedin unpublished resultsthat it is possible to vitrify and rewarm human pancreatic islets with excellent islet number recovery and excellent retention of viabilitybased on vital stainingglucose stimulated insulin releasestimulation indexglucose stimulated oxygen consumptionand ability to reverse induced diabetes in mice with minimal islet dosesand we are working on scaling up fromIEQs per vitrified batch to full curative doses of isletsThe next step is to establish that islets remain highly viable and functional following at leastweeks of storage and to determine the best storage conditions for isletsThe best storage conditions are postulated to be quite unconventional due to the large volumes associated with vitrifying all islets from a single donorthe fact that the islets will be vitrifiedand the desirability of rapid transfer into and out of long term storage without any risk of fracturingIn particularwe believe that islets should be stored near TGand possibly even above TGbut storage in this temperature range has not been previously studied in any adequate wayAccordinglyAimis devoted to determining the effect of temperature on islet viability and functionalityAimis directed toward determining the effect of temperature on ice nucleation in both the islets and their vitrified medium and the relationship between ice nucleation and islet integrityand Aimis intended to determine the effect of storage time beyondmonthOne month of storage should be sufficient for most islet banking needsbut two months would be very valuable for providing a safety margin and more flexibility to the clinician and the patientAt the same timecomparingandmonths of storage will open up information about rates of nucleation over time near TG that is presently entirely lackingand will begin to answer questions about biological stability near TG that presently remain entirely obscure Project Narrative The ultimate objectives of this application are to enable improved treatment of typediabetesT Dby establishing islet banking capability and to advance the science of cryobiology and cryopreservation in general by mapping the effects of time and temperature on islet integrity and on ice nucleation near the glass transition temperatureTGIslet banking would allow islet transplants following transplantation of kidneys from the same donor at leastweeks earlierreducing ultimate islet rejectionIt would also provide more time for tolerance induction during islet storage and encourage collection of many more pancreases knowing that they can be used and not wastedamong other important benefitsTo optimize islet bankingwe propose to store islets near and even above TG based on a number of theoretical advantages of this temperature regimeincluding the prevention of fracturing and the ability to retrieve the islets from storage rapidly and without hazardsWe will determine the effects ofandmonths of storage at temperatures well above TG to temperatures far enough below TG to fully suppress ice nucleation and determine if the kinetics of biological deterioration are related to ice nucleation in either the vitrification solution or in the islets themselveswhether nucleation in islets differs from nucleation in solutionsand whether nucleation continues for more than a month at any temperatureNucleation densities will be followed by changes in devitrification tendencyas measured by differential scanning calorimetry using previously established protocols and by photographic evidence of devitrification upon warmingWe will also investigate fracturing tendency and document any fracturing photographicallyThe biological effects of all storage conditionswhich includes vitrification followed by immediate rewarmingstorage time of zero monthswill be evaluated by rigorous methods in standard use at the City of HopeOur laboratory has previously demonstrated excellent number recoveryviabilityglucose stimulated insulin releaseglucose stimulated oxygen consumption responsesand ability to cure induced T D in mice with the subcapsular transplantation of minimal islet dosesand we are currently scaling up this process to the vitrification of full clinical islet dosesThe final step is to establish ideal storage conditions for islets and to advance the science of cryobiology by evaluating circum TG storage for the first timepotentially opening up a new form of biological storage for future exploitation for many other biological systems while answering a number of currently obscure but fundamental questions about biological rates of change near TGThese questions are particularly relevant to all large volume biological vitrification systemsand especially to whole organswhich represent another area of currently intense scientific scrutiny
Tagged as:
SBIR
Phase I
2019
HHS
NIH
Whole Ovary Vitrification for Fertility Preservation
Amount: $172,694 Topic: NICHD
The long term goal of this proposal is to develop a safeeffective and user friendly vitrification system for cryopreservation of whole human ovariesIn the U Sovergirls and women ageare diagnosed with cancer annuallyWhile improved diagnosis and treatment have led to increased survival ratesin premenopausal andin childhood cancer patientsdevastating side effects of cancer therapies include premature ovarian failureinfertility and menopause related health risksWhile cryopreservation of embryos and oocytes are effective and will remain as the most commonly used fertility preservation methodovarian cortex and whole ovary cryopreservation is the only option for future fertility in prepubertal patients and those who require immediate cancer treatmentCryopreservation of whole ovariescompared to ovarian tissuehas added advantages ofpreserving all classes of follicleswhich can be used for in vitro maturationlonger graft lifespanandfaster recovery supported by existing blood vessels after transplantation with vascular anastomosisHowevercurrent methods for whole ovary cryopreservation are suboptimal and there is no live birth in human from cryopreserved whole ovariesdespite it may be the best choice for prepubertal cancer patients for future fertility and intact endocrine function for decades without the help of exogenous hormonesThe proposed research is part ofst Century Medicine s more general program of developing superior cryopreservation systemincluding cryoprotective agentCPAsolutionsperfusion apparatushardware and softwarefor CPA loading and unloadingand liquid nitrogen storage unitsfor organsOur company has successfully demonstrated functional preservation of vitrified rabbit kidneys after transplantationThe pig and human ovaries are similar in size and smallergramscompared to rabbit kidneysgramswhich makes vitrification of pig and human ovaries more achievable than rabbit kidneysIn this SBIR Phase I studywe will establish optimal perfusion parameters and CPA combination that will allow the preservation of follicles and blood vessels in whole swine ovariesand design an ovary specific perfusion apparatusAimWe will also optimize cooling and warming ratesand determine whether radiofrequency heating can be utilized to improve efficiency and uniformity during rewarming of vitrified swine ovariesAimOvarian function will be evaluated in vitro by ovarian tissue culturehistology and immunohistochemistrypreantral follicle culturesurvivalantrum formationhormone productioncumulus oocyte complex cultureoocyte maturationResults from these studies will improve current technology in whole ovary cryopreservation and include a design and prototype of an automated vitrification systemFuture Phase II studies will focus on construction of the vitrification apparatus incorporating aspects of perfusioncoolingstorage and rewarming with a userfriendly computer interfaceThis novel system will be tested in vivoto demonstrate livebirth in the swine model after transplantationand in vitroto test ovarian function using human ovariesin Phase II One devastating side effect of cancer treatment is premature ovarian failure which can lead to infertility and long term health risks associated with menopauseCompared to existing fertility preservation methodsembryooocyte and ovarian tissue cryopreservationwhole ovary cryopreservation offers complete recovery of ovarian functionendocrine and fertilitywhich is important for youngespecially prepubertalcancer patientsHowevercurrentlyno live birth has been demonstrated from cryopreserved whole human ovaries due to the lack of perfusion system and optimal cryopreservation protocolsThe goals for this Phase I SBIR proposal are to establish optimal perfusion as well as cryopreservation conditions for the whole ovary and design a noveleffective and user friendly vitrification apparatususing the swine ovary as an animal model
Tagged as:
SBIR
Phase I
2018
HHS
NIH
Development of Apparatus for the Vitrification of Curative Doses of Human Islets for Transplantation
Amount: $219,632 Topic: 200
Project Summary Abstract The ultimate objective of the proposed research is to enable the long term banking of curative doses of human pancreatic islets for the reversal of typediabetes and the amelioration of typediabetesBanking should reduce or prevent the deterioration of islets prior to usefacilitate tolerance inductionenable single rather than multiple islet infusions to achieve remission of typediabetesenable use of many more islets for therapeutic or research purposesand have other advantagesWe have already demonstratedin unpublished resultsthat it is possible to vitrify and rewarm human pancreatic islets with excellent islet number recovery and excellent retention of viabilitybased on vital stainingglucose stimulated insulin releasestimulation indexglucose stimulated oxygen consumptionand ability to reverse induced diabetes in mice with minimal islet dosesThe goal of the proposed research is to demonstrate that it is possible to scale up from the islet numbers vitrified to dateup toIEQsto curative doses of isletswith no significant changes in cryoprotection techniquecooling rateor warming rateThis goal will be achieved by improving the spatial efficiency of the apparatus already created while simultaneously increasing the carrying capacity of that apparatusAimmilestoneis devoted to optimizing the balance between the rate of introduction of cryoprotective agents and the behavior of the islets within one specific and nominally optimal device designAimmilestonewill be devoted to exploring the design space of the device based on empirical observations of the responses of islets to different carrying capacity modelsIn Aimwe will fabricate and preliminarily test the optimized device resulting from the information gained in AimThis device will be mostly automated to enable use by relatively unskilled personnel and to prevent variations caused by operator factors or operator errorIn Aimwe will test the optimized device and method by actually vitrifying islets in densities within the device equivalent to the densities that will be required for preserving fully curative clinical islet dosesand the results will be evaluated independently by the City of Hope using the abovedescribed endpointsFinallyin Aimwe will obtain an objective evaluation of the barriers to clinical use of our methods and device as prepared by the City of Hopeand we will prepare a plan for overcoming any remaining barriers to clinical application based on the City of Hope reportThis should enable us to move forward toward clinical trials of vitrified curative doses of human pancreatic islets Project Narrative The ultimate objective of this application is to enable the cure of typediabetesT Dby making it possible to aprovide pancreatic islets to T D patients at optimal times and with minimal islet deterioration prior to transplantationbprovide tissue engineered substitutes for pancreatic islets when they become available by removing inventory control obstaclesthereby enabling all T D victims to receive curative insulin producing cellsand cinduce immunological tolerance to islet transplantsthereby overcoming both ordinary rejection and autoimmune rejectionThe common denominator between all of these requirements for curing T D is the ability to bank islets in excellent condition as long as may be required to aenable their transplantation into recipients under ideal conditionsbeliminate mismatches between the moment to moment supply and demand of laboratory produced islet replacementsand cenable tolerance to be induced prior to or simultaneously with the transplantation of donor or laboratory produced islets or islet equivalentsOur laboratory has already demonstrated the ability to bank human islets with excellent number recoveryviabilityglucose stimulated insulin releaseglucose stimulated oxygen consumption responsesand ability to cure induced T D in mice with the subcapsular transplantation of minimal islet dosesand thereforethe purpose of the present application is simply to scale up our existing successful methods to enable the vitrification of curative doses of human isletswhich appears to be quite possible based on preliminary calculations
Tagged as:
SBIR
Phase I
2018
HHS
NIH
Automated High Throughput Cryopreservation Using Microfluidics
Amount: $251,046 Topic: NCRR
DESCRIPTION (provided by applicant): The long-term objective of this research is to develop a device that will improve the efficacy of cryopreserving cells in suspension and small pieces of tissue. Having improved means for cell and tissue cryopreservation can increase the effectiveness of bioresource centers containing banks of high quality cells and tissues for research. It can also provide cryopreserved cells for direct patient therapy (e.g. oocytes and ovarian tissue for fertility preservation, stem cells and pancreatic islets for transplantation). The objectives of this Phase I application are to develop a microfluidics cryopreservation system based upon an existing system designed for cell culture and imaging. The current system will be significantly modified in a manner that will allow it to deliver precise concentrations of solutions containing cryoprotectants at temperatures ranging from + 37 to -20 degrees C for cryopreservation of suspended cells. This will facilitate rapid cryoprotectant diffusion into cells before cryopreservation, and dilution out of cells after cryopreservation. It will also allow cells to be exposed to cryoprotectants at reduced temperatures, mitigating chemical toxicity. The aims of this project are to determine means to rapidly mix combinations of solutions and to determine the appropriate flow rates for solutions of varying viscosity. We also plan to design a new microfluidics chip specifically for cryopreservation applications as well as a cooling unit to accompany the existing hardware; a capability that the current device lacks. Mixing will be assessed by analysis of digital images taken of the solution in the final flow path, where metallic microspheres have been suspended into one of the initial solutions. Appropriate flow rates will be determined by assessing the properties of microspheres suspended in the solutions during flow. With such an instrument, high throughput cryopreservation for suspended cells and small tissue can be accomplished, significantly reducing the financial and technical burden associated with cryopreserving laboratory animal germplasm, and also offers a more accurate and reproducible means to archive cells and tissues for research and therapeutic uses. PUBLIC HEALTH RELEVANCE: The proposed research is designed to develop a device that will facilitate making improvements in methods to preserve cells and small pieces of tissue using very low temperatures (cryopreservation). Cryopreserved cells and tissues are important for many reasons, such as direct medical therapy (e.g. transplantation of blood cells), and also for providing consistent biological samples for scientific study by numerous researchers (e.g. when studying cancer or other chronic diseases). Such a device will also significantly increase the efficiency of cryopreserving germplasm from laboratory animals, reducing the overall costs to public agencies for storage and distribution of these valuable research tools.
Tagged as:
SBIR
Phase I
2010
HHS
NIH
Neural Tissue Vitrification
Amount: $184,915
DESCRIPTION (provided by applicant): The ultimate aim of the proposed research is to provide a new and practical methodology for improved preservation of neural tissues by means of vitrification technology under development at 21st Century Medicine. In phase 1, a range of cryoprotectant formulations, in combination with various carrier solutions, will be tested on rabbit hippocampal slices. Also included in the experimental design will be time and emperature variables for the purpose of optimizing tissue loading and unloading protocols, and warming and cooling rates for the purpose of optimizing vitrification characteristics. A range of electrophysiological and chemical measurements will be performed on the tissues after treatment to assess tissue functionality. The expected result of the phase 1 experiments is the demonstration that vitrification technology previously tested on other tissues can be successfully applied to neural tissue. In phase 2, information resulting from the optimization of variables from phase 1 will be used to generate final product configurations for the chemical formulations and associated apparatus necessary to facilitate the physical inventory of preserved neural tissue slices for commercial use. Direct confirmation of the practical utility of such cryopreserved tissue, in cooperation with industrial users, for ADME studies and other medical applications, will also be a part of phase 2. An improved, practical, preservation (by vitrification) methodology for neural systems (neurons, neuronal cell lines and neural tissues) opens the door to a variety of important improvements relating to public health and costs. The possibility of long-term storage of fragile and irreplaceable neural tissues and cell lines will allow for improved logistics, and true neural tissue banking. This will also have the effect of reducing costs by reducing the need for research animals and methods currently employed to obtain such tissues. Improved preservation of transplantable neural cells and tissues also makes possible benefits in the treatment of public hearth issues such as Parkenson's, Alzheimers, stroke, and spinal cord injuries. It is also possible this technology may be useful in the creation of systems to monitor for the presence of environmental neural toxins in military or antiterrorist applications.
Tagged as:
SBIR
Phase I
2006
HHS
NIH
Extended Cardiac Preservation
Amount: $835,104
DESCRIPTION (provided by applicant): The long-term objective of this project is the commercialization of a product(s) that enables a substantial improvement in human heart preservation prior to transplantation. The ability to significantly extend human cl
Tagged as:
SBIR
Phase II
2004
HHS
NIH
Cornea Preservation by Vitrification
Amount: $195,024
Each year over 33,000 human corneas are transplanted in the United States. However, currently available cornea storage protocols affect deleterious changes in all layers of the cornea, which limit permissible local storage times and largely preclude adequ
Tagged as:
SBIR
Phase I
2004
HHS
NIH
Improved Renal Preservation
Amount: $154,641
DESCRIPTION (provided by applicant): The ultimate aim of the proposed research is to enable a substantial improvement in human kidney preservation prior to transplantation by extending the safe storage time and improving outcomes after any given period of storage. This proposal will build upon existing results indicating that a new renal preservation solution developed at 21st Century Medicine (Renasol) is superior to the industry standard, UW solution, in both canine and leporine renal transplant models. The proposal will explore a combination of Renasol and a specific new formulation of protein factors ("trophic factors") that dramatically improve hypothermic storage of dog kidneys. More information will be obtained on the appropriate concentration of trophic factors using the rabbit renal transplant model. A potentially valuable additive for Renasol that may help protect human kidneys from the effects of agonal hypotension will also be evaluated. Canine renal transplants will also be performed using kidneys preserved by simple cold storage for 4 days with Renasol and with Renasol + trophic factors. In anticipation of clinical application, and resulting stability requirements, tests will be conducted, using both the canine and leporine models, to show Renasol retains its effectiveness after months of prior storage at 4 deg. C. These studies will result in a final formulation that will be taken into human clinical trials in Phase II and marketed in Phase Ill. During the course of the proposed studies, urine samples will be collected on a routine basis and subjected to protein profiling using an in-house proteomics workstation. These observations will determine whether the degree of hypothermic injury observed is correlated with definable relative or absolute changes in urinary protein concentrations. This may provide a new predictive diagnostic marker of renal preservation injury. The ability to preserve kidneys with less damage prior to transplantation will significantly reduce the costs and risks of post-transplant dialysis, reduce rejection episodes, and increase the net organ supply.
Tagged as:
SBIR
Phase I
2003
HHS
NIH
EXTENDED CARDIAC PRESERVATION
Amount: $164,852
Description (provided by applicant): The research proposed is designed to enable a substantial improvement in human heart preservation prior to transplantation. The model involves preservation of canine hearts and evaluation by transplantation and functional assessment over a 6-hour observation period following weaning from cardiopulmonary bypass. Preliminary results indicate excellent recovery of 5 out of 5 hearts after preservation for 40 hours. We propose the development of a very simple yet highly effective preservation device that should enable clinicians to employ the new preservation method without difficulty, safety concerns, or substantial expense. Phase I primarily seeks to show that unattended use of the device yields preservation quality that equals what has been obtained previously with manual methods. Phase II would further employ the device to fully optimize this highly promising method in preparation for human clinical trials, which can be done at the Research Institution when warranted. It is now accepted that excellent matching between donors and recipients can result in at least a 50 percent increase in survival rate 10 years after transplantation. The ability to extend human clinical cardiac preservation to 40 hours would allow transcontinental prospective matching, with expected substantial gains in clinical outcome for potentially thousands of heart transplants recipients. PROPOSED COMMERCIAL APPLICATION: Potential commercial applications include marketing of devices, disposables, protocols, software, and upgrades used in the preservation of hearts, other organs, and engineered tissues for transplantation.
Tagged as:
SBIR
Phase I
2002
HHS
NIH