A Wearable Bioreactor to Study Limb Regeneration In Vivo using an Adult Murine Digit Amputation Model.
Golding, Anne.
2019
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In the United States
approximately 185,000 people annually suffer from a limb amputation. Limb regeneration
has been designated one of the top goals in fields of biomaterials and regenerative
medicine, but is unattainable due to our lack of knowledge of the biology that drives
limb regeneration. The fields of developmental and regenerative biology study the
different pathways that define limb ... read moreregeneration using animal models capable of this
phenomenon. One of the few mammalian models of limb regeneration is the mouse digit tip
amputation model. The resulting research has furthered our understanding of the
fundamental mechanism that controls limb regeneration. However, in order to translate
this fundamental knowledge into application, a system that can control activities at the
amputation site, including hydration and drug delivery, is needed. In this thesis we
present a solution to this issue with a wearable hydrogel based bioreactor for the
studying limb regeneration in vivo using the mouse digit tip amputation model. The work
presented demonstrates a robust system capable of handling the rough in vivo
environment. The device was used to study the static and dynamic role of macrophage
polarization towards limb regeneration. With static delivery, three different cytokines
(interferon gamma, interleukin 4, and interleukin 10) were utilized to induce the
different polarization states (M1, M2a, and M2c, respectfully). The different deliveries
resulted in distinct immune profiles 5-day post amputation (DPA) that altered the wound
healing and hydrogel interactions at later time-points (15 DPA and 28 DPA). Next we
applied two methods of drug delivery to dynamically manipulate the local macrophage
population with temporal and spatial control of two polarizing cytokines in a single
treatment. The results confirmed the efficacy of both treatments at 5 DPA with
differences in morphology in the wound bed, as well as variations in the immune profile
(cell recruitment and macrophage polarization at the wound site). Overall the results
demonstrate the capabilities of this system to be used in mouse studies to further our
understanding of limb regeneration.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: David Kaplan.
Committee: Clifford Tabin, Ayse Asatekin, and Qiaobing Xu.
Keyword: Chemical engineering.read less - ID:
- 8623j969v
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