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Faculty Liisa T. Kuhn
Assistant Professor of Oral Rehabilitation, Biomaterials and
Skeletal Development, Center for Regenerative Medicine and Skeletal
Development
lkuhn@uchc.edu
Areas of Interest:
Calcium phosphates have long been used for medical applications because
of their excellent biocompatibility, lack of toxicity, and
osteoconductivity. My research is focused on the use of calcium
phosphate for the local delivery of either chemotherapy drugs or bone
stimulating factors. Calcium phosphate has advantages over some
polymer-based delivery systems because the slow degradation/dissolution
of calcium phosphate crystals occurs without acidic byproducts that may
damage surrounding tissues or affect the stability of the attached
drugs. We use a three-fold approach to developing drug delivery systems:
(a) chemical formulation, including controlled release studies, (b)in
vitro cytotoxicity assays with cell lines to confirm drug activity, and
(c) in vivo mouse models for evaluating improved drug effectiveness and
reduced systemic toxicity. Three different recent mouse studies have
shown that our calcium phosphate/cisplatin drug delivery system is more
effective than systemic cisplatin at reducing tumor growth, and is less
toxic to normal tissues. We are also working with an implant dentist at
the Health Center to improve bone growth around dental implants. The
animal studies conducted this far confirm that localized delivery of
bone morphogenetic agents on a dental implant can increase vertical bone
growth substantially over conventional treatments.
Research Interests:
Biomaterials for:
- Sustained release of active biomolecules and pharmaceuticals.
- Repair and regeneration of bone using biomaterial scaffolds.
- Cell culture plate coatings for expansion and differentiation of human
embryonic stem cells.
Lab Rotation Projects:
Implant Guided Bone Growth Mediated by Local Delivery of Osteogenic
Agents
The purpose of this research is to develop dental implant guided bone
augmentation procedures for the reconstruction of the resorbed alveolar
ridge of the mandible. This work is done in collaboration with Dr.
Martin Freilich, Dr. David Shafer, and Dr. Robert Kelly. Our goals are
to deliver locally acting osteogenic agents from bioactive implant
surfaces or scaffolds to guide new supracrestal alveolar bone formation
at resorbed sites. Towards this end, we have recently developed novel
study models utilizing both miniaturized and full sized titanium implant
components to deliver osteogenic agents or stabilize scaffolds for
guiding the growth of a new layer of intramembraneous bone. We first
complete in vitro drug release studies to ensure active growth factor
release from the scaffolds, and then test the dental implant systems in
small and large animals to prove efficacy.
Tissue Engineering
In collaboration with Dr. A. Jon Goldberg we are studying how tissue
engineering scaffolds can be designed to influence the development of
human embryonic stem cells (hESCs). This project is part of a large
program lead by Dr. David Rowe on directing hES derived progenitor cells
into musculoskeletal lineages, funded by the Connecticut initiative on
human embryonic stem cells. Hydroxyapatite and collagen-based scaffolds
are prepared in the laboratory and characterized with SEM, EDS, XRD,
FTIR, optical microscopy and profilometry prior to cell culture
experiments. Hyaluronan hydrogels are additionally being investigated as
animal-free, feeder-free substrates to support hES cell expansion
without differentiation. The response of various cell types to the
scaffolds are monitored with traditional biomarkers and novel
fluorescent labelling techniques.
Targeted Delivery of Anti-Cancer Agents
Calcium phosphates have long been used for medical applications because
of their excellent biocompatibility, lack of toxicity, and
osteoconductivity. This research project is focused on the use of
calcium phosphate for the local, less-toxic delivery of chemotherapy
drugs. We use a three-fold approach to developing drug delivery systems
from calcium phosphate particulates: (a) in vitro drug binding and
release studies, (b) in vitro cytotoxicity assays with cancer cell
lines, and lastly (c) in vivo mouse models for evaluating inhibition of
tumor growth, metastasis, and reduced systemic toxicity. Our most recent
results indicate that our injectable calcium phosphate/cisplatin
nanoconjugates can inhibit mouse breast cancer lymph node metastasis, as
effectively as a systemic dose, with fewer toxic side effects.
Selected Publications:
LT Turner, R Yadav, TV Rajan, AT Vella, and LT Kuhn, Effects of the
Physico-Chemical Nature of Two Biomimetic Crystals on the Innate Immune
Response. Int. Immunopharmacology 7: 1617-1629 (2007).
X Cheng and LT Kuhn. Chemotherapy Drug Delivery from Calcium
Phosphate Nanoparticles, Int. J. of Nanomedicine. 2(4):667-674 (2007).
LT Kuhn, Biomaterials, Chapter 6 in Introduction to Biomedical
Engineering, Eds. JD Enderle, S Blanchard, and JD Bronzino, Elsevier,
2005.
MA Freilich, M Wei, S Iddir, LT Kuhn, and DM Shafer, "Improvement of
Alveolar Bone Height Using Novel Graft Placement", Key Eng. Mater.
(Proceedings of Bioceramics 17 Conference), 284-286, 889-892 (2005).
A. Barroug, LT Kuhn, LC Gerstenfeld, MJ Glimcher. Interactions of
cisplatin with calcium phosphate nanoparticles: in vitro controlled
adsorption and release, J. Ortho. Res. 22:703-708 (2004).
W Tong, MJ Glimcher, JL Katz, LT Kuhn, SJ Eppell. Size and Shape of
Mineralites in Young Bovine Bone Measured by Atomic Force Microscopy,
Calcified Tissue International, 72: 592-598 (2003). |
