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Evaluating the Safety and Efficacy of Cartilage Regeneration with Tunable Inflammation Resistance

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AR073716-01
Agency Tracking Number: R43AR073716
Amount: $225,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIAMS
Solicitation Number: PA17-302
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-09-18
Award End Date (Contract End Date): 2019-08-31
Small Business Information
2608 ERWIN RD, STE 19A
Durham, NC 27705-4597
United States
DUNS: 783502466
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (919) 912-9839
Business Contact
Phone: (919) 912-9839
Research Institution

The repair of large cartilage lesionswhich often lead to osteoarthritisOAremains a significant clinical problem
with few good treatment optionsPrevious work at Cytex has focused on the developing of aD woven textile
scaffold for cartilage repairdesigned to function immediately upon implantationwhile encouraging cell ingrowthproliferationand subsequent tissue developmentBy combining this proprietaryD woven implant with adiposederived stem cellsASCswe have demonstrated the ability to generate largeanatomically shaped cartilage
constructs with biomimetic mechanical propertiesNeverthelessfor a cell based cartilage therapy to be
successful in an OA patientit must withstand the catabolic effects of joint inflammationwhich are mediated by
the action of elevated levels of pro inflammatory cytokines such as interleukinILand tumor necrosis factor
alphaTNFaHoweverbecause of the pleiotropic role of ILand TNFa in vivolong term sustained anticytokine therapy is not recommendedThereforethe objective of this project is to evaluate the safety and
efficacy of an engineered functional cartilage replacement capable of protecting itself from OA inflammation by
producing an anti cytokine therapyTo this endwe propose to use an inflammation responsive promoter to drive
expression of therapeutic factorsspecificallyILreceptor antagonist and soluble TNF receptorThis will
create an auto regulated system in which cells express and secrete anti cytokine proteins only when
inflammatory signaling is presentIn Aimwe will modulate the lentiviral transduction process in an effort to
minimize the risk of genetic side effects in our biomimetic cartilage implantOur goal is to minimize the number
of viral integration events in each cellwhile maintaining a high transduction efficiencyso that the ASCs in our
implant can effectively deliver the anti cytokine therapyIn Aimour engineered cartilage will be implanted
subcutaneously in an inflammatory mouse model to test the construct s ability to sense and prevent catabolic
degradationSerum will be collected from the mice longitudinally to measure the levels of inflammatory cytokines
present in the modelas well as the levels of anti cytokine therapeutics produced by our implant in direct
response to the inflammatory cytokinesAt sacrificethe cartilage constructs will be excised and assessed
histologicallybiochemicallyand biomechanically to quantify any degradative changes that have occurred in the
tissueAdditionallyall major organ systems of the mice will be examined histologically to assess the safety of
implanting transduced cells and utilizing anti cytokine therapyThis proposal addresses the clinical need for
large functional cartilage replacements that can thrive in an inflamed osteoarthritic jointand couldas a
consequencehave a major impact on the treatment paradigm of this disease OsteoarthritisOAis one of the leading causes of disability in the worldand while a totaljoint replacement is a highly successful treatment option for patients older thanyearsof agethere areunfortunatelyno good current treatment options for the young patientpopulation suffering from this diseaseThe objective of this study is to further the developmentof abiosyntheticimplant that can both replace diseased cartilage and also detect and respond todegradative inflammation to protect the long term integrity of the implant

* Information listed above is at the time of submission. *

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