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Liisa T. Kuhn, Ph.D.Professor of Biomedical Engineering
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- Overview
- Education & Training
- Clinical Interests
- Teaching
- Committees & Organizations
- Research
- Research Opportunities
- Lab Rotations
- Publications
Dr. Kuhn’s laboratory works at the interface of materials science and medicine and spans fundamental studies to translational research. She has an expertise in drug delivery and bone regeneration that she gained while working in industry and at UConn Health. She is funded by the National Institutes of Health to develop customized bone grafts for older patients that include controlled release of anti-senescence drugs to rejuvenate bone healing in the elderly. She is Director of the Beekley Lab for Biosymmetrix since Spring 2021. This project is 3D printing personalized breast prostheses for breast cancer survivors at UConn Health’s Carole and Ray Neag Comprehensive Cancer Center. The project has been funded by the Connecticut Breast Health Initiative and the Beekley Family Foundation.
The Kuhn Lab's mission is to develop biomaterial technologies to restore or regenerate damaged or diseased tissue.
Degree | Institution | Major |
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B.S. | Duke University | Mechanical Engineering |
M.S. | University of California | Materials Engineering |
Ph.D. | University of California | Materials Engineering |
Post-Graduate Training
Training | Institution | Specialty |
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Postdoctoral | Case Western Reserve University | Biomineralization |
Awards
Name of Award/Honor | Awarding Organization |
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Women of Innovation Award, Academic Innovation and Leadership Category | Connecticut Technology Council |
Patrick Laing Award for Outstanding and Meritorious Service | American Society of Testing and Materials (ASTM) |
Dr. Kuhn (Ph.D.) conducts preclinical testing of promising dental and orthopedic technologies that can improve bone regeneration.
Dr. Liisa Kuhn trains the next generation of scientists by advising undergraduate, graduate and postdoctoral trainees and giving lectures in her own courses and others. She developed and taught the UConn biomedical engineering core course called BME 4710/5700 Biomaterials and Tissue Engineering for eight years. In 2014 she created a new, follow-on course that is a combined undergrad/grad course and taught every spring: Controlling Stem Cells With Biomaterials, listed as BME 4985-003/BME 6086-004.
Course Description: In this course participants will learn how to design biomaterials that actively control stem cells to achieve tissue regeneration. Biological and biomaterials principles will be taught with a focus on cell/extracellular matrix interactions during embryonic development and wound healing. Biomaterial and biomechanical techniques to influence the attachment, proliferation and differentiation of stem cells on a biomaterial scaffold will be studied including: chemical and physical modifications of biomaterials, use of natural tissues as scaffolds and bioreactor culture.
Dr. Kuhn also serves as Faculty facilitator for D400-720 Critical Thinking in Dentistry and Correlated Dental Problem Solving. It is a two semester course.
Mentoring and Outreach Lectures 2005 & 2006 Lecturer. Capital Community College. Discoveries in Modern Medicine at Capital Community College, Hartford, CT. Course Director: M. Mednieks. Bridges to Baccalaureate outreach program to underrepresented minorities in science. Fall semester.
2009 “A Day in the Life of a Research Scientist” Career Panel Speaker, Connecticut DigiGirlZ program for minority high school students. Microsoft Corporation. March 27, 2009.
“Women in Science and Engineering”, Keynote speaker, Annual Banquet of Women in Math, Science and Engineering, University of Connecticut Storrs Campus, CT. April 15, 2009.
“A Career in Biomedical Science and Engineering” Panelist for Career Paths in the Sciences, organized by the Women in Math, Science and Engineering (WiMSE). University of Connecticut Storrs Campus, CT. November 30, 2009.
2010 “Making the Transition from Industry to Academia” Panelist at the annual retreat of the Skeletal, Craniofacial and Oral Biology, Biomedical Sciences Graduate program. UConn-Avery Point, CT. June 12, 2010.
2011 “University Partnerships using the NIH SBIR Small Business Grants Program”, Panelist at the Connecticut Innovations Regional NIH SBIR workshop. UConn-Health Center, Farmington, CT. October 20, 2011.
Name & Description | Category | Role | Type | Scope | Start Year | End Year |
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Editor, Biomaterials Forum Society For Biomaterials | Professional/Scientific Organization | Editor | External | National | 2011 | |
General Interest Vice-Chair of the Main Committee F04 Medical and Surgical Materials and Devices, American Society of Testing and Materials (ASTM) | Professional/Scientific Organization | Vice Chair | External | National | 2004 | 2012 |
NIH CSR Study Section Member (NIAMS, SBIR/STTR), Ad hoc member - present. | Study Section | Member | External | National | 2003 | |
Overall Meeting Program Chair, 28th Annual Meeting of the Society for Biomaterials | Professional/Scientific Organization | Chair | External | National | 2002 | 2002 |
The Kuhn lab's research mission is to bring regenerative and anti-cancer biomaterials technologies closer to patient use through pre-clinical testing and research.
Bone morphogenetic protein-2 (BMP-2) is now used clinically in patients to enhance bone regeneration during spinal fusion, fracture healing and dental bone implant procedures. While BMP-2 has been demonstrated to significantly enhance bone repair, the complication profile, likely related to the supraphysiologic dose of BMP-2 delivered in its current formulation, has lead to safety concerns and has limited its clinical use. Reported complications include early inflammatory reaction and osteolysis, ectopic bone formation sometimes leading to compression of neural elements, seroma formation and a possible increase in the risk of malignancy. Thus, there is a need to refine the delivery and improve the efficacy of BMP-2 so that it can be delivered in lower doses with less risk of complications. The Kuhn lab is addressing the BMP-2 problem by developing a better delivery system. We are designing and testing polyelectrolyte multi-layer coated scaffolds to achieve controlled delivery of BMP-2 in conjunction with other growth factors to regenerate bone for dental and orthopedic applications.
Many older adults have a compromised ability to repair fractures or replace lost bone. It has been suggested that a decrease in numbers of osteogenic progenitor cells in elderly patients contributes to the decrease in skeletal bone formation and rate of fracture repair observed with aging and in osteoporotic patients. Further, mesenchymal stem cells in post-menopausal women have a lower growth rate and are deficient in their ability to differentiate along the osteogenic lineage. The problem of reduced bone formation in the aging mammalian body remains unsolved. While the biology of aging is complex, strategies that improve the number and function of osteoprogenitor cells in elderly patients is likely to contribute to increased bone formation; thus that is our research focus.
Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of many cell types, including osteoblasts, and is stored in the extracellular matrix. In mice, FGF receptor 2 loss of function results in progressive osteopenia and decreased bone formation rates, suggesting a role for FGF-2 in maintaining bone mass, especially with aging. Several studies by our co-investigator Dr. Hurley at our institute and others have shown that FGF-2 is a potent stimulator of preosteoblast replication. FGF-2 and platelet-derived growth factor (PDGF) were observed to be the only growth factors that increased mineralized nodule formation in calvarial osteoblasts from aged rats, and FGF-2 was twice as potent as PDGF. Whereas chronic exposure to FGF-2 can also stimulate osteoclast formation, and increase bone resorption, intermittent FGF-2 treatment stimulates bone formation in vitro and in vivo. FGF-2 has great potential to increase the activity and function of osteoprogenitor cells in elderly patients and thus we are developing biomaterial scaffolds that can delivery it locally, in combination with BMP-2 to stimulate more rapid bone healing.
FGF-2 and BMP-2 have synergistic bone enhancing effects resulting in increased bone volume as a function of dose in ectopic sites and in rat calvaria parietal bones, but the combination has been primarily testing in young animals, not old. Our current research thus studies effects of these two factors in old animals. Too much FGF-2 has been shown to reduce the amount of in vivo bone formation with BMP-2 because it can maintain cells in an undifferentiated state too long thus dose optimization is mandatory. FGF-2 enhances BMP-2 stimulated bone formation and may be the solution for reducing the dose and complications associated with BMP-2 use.
We have a major research effort investigating polyelectrolyte multi-layer (PEM) technology applied to bone substitute materials to enable sequential delivery of FGF-2 and BMP-2. The PEM technology is a thin film deposition technique that forms nanoreservoirs for drug delivery and antimicrobial protection. Bioactive proteins can be directly integrated into PEM coatings in the absence of covalent bonding and thus keep secondary structures close to their native form. The growth factors are released through cell-based PEM degradation, rather than by the undesirable non-cell initiated polymer hydrolysis which leads to burst release and may degrade the growth factor or initiate inflammation. Our work, and that of others, indicates that sequential delivery of FGF-2 followed by BMP-2, rather than co-delivery of FGF-2/BMP-2, produces the maximal osteogenic effect. Our work in this area is currently funded by the NIH NIDCR and has been presented at the Society For Biomaterials and Orthopedic Research Society annual meetings.
Recent publications in this area include:
LF Charles, JL Woodman, D Ueno, G Gronowicz, MM Hurley, LT Kuhn*. Effects of Low Dose FGF-2 and BMP-2 on Healing of Calvarial Defects in Old Mice. Exp Gerontol, 2015; 64: 62-69. http://dx.doi.org/10.1016/j.exger.2015.02.006.
L Kuhn*, G Ou, L Charles, M Hurley, C Rodner and G Gronowicz, Fibroblast growth factor-2 and Bone Morphogenetic Protein-2 Have a Synergistic Stimulatory Effect on Bone Formation in Cell Cultures from Aging Mouse and Human Bone, J Gerontol A Biol Sci Med Sci. 2013 Oct;68(10):1170-80. doi: 10.1093/gerona/glt018.
L Xiao, D Ueno, S Catros, L Charles, L Kuhn, MM Hurley. Exported 18-kDa Isoform of Fibroblast Growth Factor-2 Improved Bone Regeneration in Critical Size Mice Calvarial Defects. Endocrinology, 2014 Mar;155(3):965-74. doi: 10.1210/en.2013-1919.
If you are interested in learning about biomaterials and preclinical testing, please contact Dr. Liisa Kuhn for research opportunities.
There are no paid openings available in the Kuhn lab at this time, but volunteer positions are available.
Accepting Lab Rotation Students: Summer 2021, Fall 2021, and Spring 2022
Immunomodulation of bone healing via biomaterials and anti-senescence drugs
The long term goal of this recently funded NIH R01 project is improving bone repair in the elderly. Recently, the positive effects of eliminating senescent cells on overall bone mass has been shown. What was not investigated was the impact of senolytics or anti-inflammatory drugs on bone healing. The Kuhn lab is investigating optimizing the timing of delivery of senolytics and anti-inflammatory drugs on bone healing by using a controlled release technology that is applied as a coating on a bone graft material. Come and join us as we discover how timing of delivery impacts macrophage-osteoprogenitor-osteoclast communication and optimize delivery timing of drugs that affect senescent cells as a novel means to improve bone repair in the elderly.
Journal Articles
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Endogenous FGF-2 levels impact FGF-2/BMP-2 growth factor delivery dosing in aged murine calvarial bone defects.
Journal of biomedical materials research. Part A 2021 Jun;
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Self-assembled biomimetic Nano-Matrix for stem cell anchorage.
Journal of biomedical materials research. Part A 2020 Apr;108(4):984-991
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Cell Type Influences Local Delivery of Biomolecules from a Bioinspired Apatite Drug Delivery System.
Materials (Basel, Switzerland) 2018 Sep;11(9):
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Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings.
Biomaterials 2018 Jul;
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Calvarial bone regeneration is enhanced by sequential delivery of FGF-2 and BMP-2 from layer-by-layer coatings with a biomimetic calcium phosphate barrier layer.
Tissue engineering. Part A 2017 Sep;231490-1501
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Implant-guided supracrestal alveolar bone growth using scaffolds, BMP-2, and novel scaffold-retaining device.
Clinical oral implants research 2017 Mar;281411-1420
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Biomimetic Calcium Phosphate/Polyelectrolyte Multilayer Coatings for Sequential Delivery of Multiple Biological Factors.
Journal of biomedical materials research. Part A 2016 Dec;1051500-1509
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Layer-by-layer nanoparticle platform for cancer active targeting.
International journal of pharmaceutics 2016 Dec;517(1-2):58-66
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Human biofield therapy does not affect tumor size but modulates immune responses in a mouse model for breast cancer.
Journal of integrative medicine 2016 Sep;14(5):389-99
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Age-Related Changes in FGF-2, Fibroblast Growth Factor Receptors and β-Catenin Expression in Human Mesenchyme-Derived Progenitor Cells.
Journal of cellular biochemistry 2015 Sep;117721-9
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Comparison of bone morphogenetic protein-2 delivery systems to induce supracrestal bone guided by titanium implants in the rabbit mandible.
Clinical oral implants research 2015 Jul;27676-85
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Effects of low dose FGF-2 and BMP-2 on healing of calvarial defects in old mice.
Experimental gerontology 2015 Apr;6462-9
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Optimizing BMP-2-induced bone repair with FGF-2.
The Journal of the American Academy of Orthopaedic Surgeons 2014 Oct;22(10):677-9
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A Site-Specific Integrated Col2.3GFP Reporter Identifies Osteoblasts Within Mineralized Tissue Formed In Vivo by Human Embryonic Stem Cells.
Stem cells translational medicine 2014 Aug;3(10):1125-37
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Lithium-end-capped polylactide thin films influence osteoblast progenitor cell differentiation and mineralization.
Journal of biomedical materials research. Part A 2014 Apr;103(2):500-10
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Fibroblast growth factor-2 isoform (low molecular weight/18 kDa) overexpression in preosteoblast cells promotes bone regeneration in critical size calvarial defects in male mice.
Endocrinology 2014 Jan;155(3):965-74
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Fibroblast growth factor-2 and bone morphogenetic protein-2 have a synergistic stimulatory effect on bone formation in cell cultures from elderly mouse and human bone.
The journals of gerontology. Series A, Biological sciences and medical sciences 2013 Oct;68(10):1170-80
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Developmental-like bone regeneration by human embryonic stem cell-derived mesenchymal cells.
Tissue engineering. Part A 2013 Aug;20(1-2):365-77
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Modified hyaluronan hydrogels support the maintenance of mouse embryonic stem cells and human induced pluripotent stem cells.
Macromolecular bioscience 2012 Aug;12(8):1034-42
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Implant-guided vertical bone growth in the mini-pig.
Clinical oral implants research 2012 Jun;23(6):751-7
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One-step derivation of mesenchymal stem cell (MSC)-like cells from human pluripotent stem cells on a fibrillar collagen coating.
PloS one 2012 Mar;7(3):e33225
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Imaging tumor hypoxia by near-infrared fluorescence tomography.
Journal of biomedical optics 2011 Jun;16(6):066009
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A nondestructive method for evaluating in vitro osteoblast differentiation on biomaterials using osteoblast-specific fluorescence.
Tissue engineering. Part C, Methods 2010 Dec;16(6):1357-66
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Pro416Arg cherubism mutation in Sh3bp2 knock-in mice affects osteoblasts and alters bone mineral and matrix properties.
Bone 2010 May;46(5):1306-15
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Fabrication and characterization of hydroxyapatite-coated polystyrene disks for use in osteoprogenitor cell culture.
Journal of biomaterials science. Polymer edition 2010 Jan;21(10):1371-87
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Non-physiological mineral deposition in vitro by primary human osteoblasts under osteogenic conditions
Proceedings of the 2010 IEEE 36th Annual Northeast Bioengineering Conference, NEBEC 2010 2010 Jan;
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Implant system for guiding a new layer of bone. Computed microtomography and histomorphometric analysis in the rabbit mandible.
Clinical oral implants research 2009 Feb;20(2):201-7
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Growth of new bone guided by implants in a murine calvarial model.
Bone 2008 Oct;43(4):781-8
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A comparison of the physical and chemical differences between cancellous and cortical bovine bone mineral at two ages.
Calcified tissue international 2008 Aug;83(2):146-54
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Effects of the physico-chemical nature of two biomimetic crystals on the innate immune response.
International immunopharmacology 2007 Dec;7(13):1617-29
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A Novel Surgical Approach for Treatment of Class II Furcation Defects Using Marginal Periosteal Membrane.
Journal of the International Academy of Periodontology 2005 Jan;17(1):20-31
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Interactions of cisplatin with calcium phosphate nanoparticles: in vitro controlled adsorption and release.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2004 Jul;22(4):703-8
Abstracts
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Advanced micro- and nanofabrication technologies for tissue engineering.
Biofabrication 2011 Jan;6(2):020301
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Substantial mouse bone repair by osteo-chondrogenic progenitors derived from hESCs.
Regenerative Medicine:Innovations for Clinical Applications 2011 Jan;
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Substantial mouse calvarial bone defect healing by human embryonic stem cells
Orthopedic Research Society 2011 Jan;
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Substantial mouse calvarial bone defect healing by human embryonic stem cells.
StemCONN 2011 2011 Jan;
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Visual Monitoring of Osteoblast Progenitor Cell Differentiation on Dewetted PLA Thin Films.
Materials Research Society 2011 Jan;
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Fibrillar Collagen Thin Films Promote Early Osteogenesis
American Association for Dental Research Annual Meeting 2010 Jan;
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Non-physiological mineral deposition in vitro by primary human osteoblasts under osteogenic conditions.
Northeast Bioengineering Conference 2010 Jan;
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Variance of Extracel hydrogel compositions and the osteogenic effects on GFP-reporter preosteoblasts.
Society for Biomaterials 2010 Jan;
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Varying PLA functionality and texture to influence osteoprogenitors.
Academy of Dental Materials 2010 Jan;
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Biomimetic method for coating tissue culture polystyrene with carbonated hydroxyapaptite.
J. Dent. Res 2009 Jan; 88
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Differential effects of fibrillar and non-fibrillar collagens on osteogenesis of GFP-reporter preosteoblasts.
New England Musculoskeletal Institute Research Day 2009 Jan;
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Fluorescent quantification of osteogenesis of GFP-transgenic mouse calvarial osteoblasts on biomimetic coatings.
Society for Biomaterials 2009 Jan;
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Fluorescent quantification of osteogenesis using GFP-transgenic mouse reporter cell technology.
Regenerative Medicine-Advancing Next Generation Therapies 2009 Jan;
Conference Papers
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Non-physiological mineral deposition in vitro by primary human osteoblasts under osteogenic conditions.
2010 Jan;
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Evaluation of lymphatic metastasis using calcium phosphate/cisplatin nanoconjugates
Bioengineering, Proceedings of the Northeast Conference 2009 Jan;
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Chemoradiotherapy of ME-180 tumors with an intratumoral cisplatin/calcium phosphate drug delivery system
Bioengineering, Proceedings of the Northeast Conference 2006 Jan;2006189-190
Editorials
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Editorial: Enabling Biomaterials for New Biomedical Technologies and Clinical Therapies.
Frontiers in bioengineering and biotechnology 2020 Jan;8559
Erratums
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Erratum: A comparison of the physical and chemical differences between cancellous and cortical bovine bone mineral at two ages (Calcif Tissue Int (2008) 83:2 (146-154) DOI: 10.1007/s00223-008-9164-z)
Calcified Tissue International 2009 Jan;84(4):335
Letters
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Response to the letter "Age and site should be considered when investigating the effect of growth factors on human bone-derived cells".
The journals of gerontology. Series A, Biological sciences and medical sciences 2014 Jul;69(9):1092-3
Reviews
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Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering.
Dental materials : official publication of the Academy of Dental Materials 2016 Jan;32(1):43-53