VUSEVU Biomedical Photonics





Alex Makowski

BE Biomedical Engineering, 2007
MS Biomedical Engineering, 2010
Vanderbilt University

Phone: 615-343-8946

 Email: A.Makowski@Vanderbilt.edu

Research

Interests: Bone Quality; Raman Spectroscopy; Extracellular Matrix Disease; Hard Tissue Biomechanics; Fracture Toughness; Laser-Tissue Interactions; Laser Preconditioning of Skin; Wound Healing

My research interests focus on the identification of Raman spectroscopy parameters and methods that best explain and diagnose diseases and flaws of the extracellular matrix, with a current focus on bone quality. There is a rising incidence of bone fracture and a growing population of undiagnosed patients at risk for fracture. Current clinical diagnostics of bone, based upon x-ray and epidemiology, are largely limited to the mineral phase of bone, while Raman spectroscopy methods examine mineral and collagen phases concurrently.  Because Raman is conducted without ionizing radiation, in near real time, and at low operating costs, Raman Spectroscopy has become strong candidate for a clinical complement to established x-ray diagnostics.

Specifically my PhD thesis investigates how elements of the Raman spectra, derived biomarkers, and multivariate spectral signatures explain the toughness and fracture toughness of bone.  Current diagnostics explain the strength of bone well, but not its toughness.  Essentially, brittle bones break despite sometimes high tissue mineral density as viewed by x-ray or micro-computed tomography.  Moreover, bone, like all materials, has flaws. The propagation of flaws  plays an important role in any material’s resistance to failure. Bone’s resistance to propagation of these micro-cracks is referred to as its fracture toughness. Using various known models of bone brittleness, including aging and disease, I correlate biomechanical properties to spectral properties to increase our knowledge of bone fracture resistance, while driving Raman spectroscopy methods towards clinical application.

My Master’s thesis work focused on the extracellular matrix healing in skin. Infrared laser preconditioning has been shown by our lab and others to improve healing, and laser treatment parameters were previously tuned using heat shock protein biomarkers. To test the hypothesis that heat shock protein 70 (HSP70) was essential to the mechanism of healing improvement due to laser preconditioning, we conducted the laser preconditioning and incisional wounding in HSP70 -/- and HSP70 +/+ animal models. We conducted what we believe to be the first in vivo analysis of wound healing by Raman spectroscopy, confirming the known time course of treatment effects, and demonstrating biomarkers that showed separate biochemical changes during early inflammatory stages and late healing that extended into remodeling.

Publications

Journal articles:

Makowski AJ, Patil CA, Mahadevan-Jansen A, Nyman JS. Polarization Control of Raman Spectroscopy Optimizes the Assessment of Bone Tissue. J Biomed Opt (In Press)

Makowski AJ, Davidson JM, Mahadevan-Jansen A, Jansen ED. In vivo analysis of laser preconditioning in incisional wound healing of wild-type and HSP70 knockout mice with Raman spectroscopy. Lasers Surg Med (2012) 44: 233-44.

Nyman JS, Makowski AJ. The contribution of the extracellular matrix to the fracture resistance of bone. Curr Osteoporos Rep (2012) 10: 169-77.

Nyman JS, Makowski AJ, Patil CA, Masui TP, O'Quinn EC, Bi X, Guelcher SA, Nicollela DP, Mahadevan-Jansen A. Measuring differences in compositional properties of bone tissue by confocal Raman spectroscopy. Calcif Tissue Int (2011) 89: 111-22.

 

Conference Proceedings:

Makowski AJ, Mahadevan-Jansen A, and  Nyman JS. Polarization Raman Spectroscopy to explain rodent models of brittle bone. Proc. SPIE 8565, Photonic Therapeutics and Diagnostics IX, 85656L: 2013. San Francisco, CA, USA.

Conference Abstracts:

Makowski AJ, Mahadevan-Jansen A, and  Nyman JS. Polarization Raman Spectroscopy Mapping Signifies Age-Related Changes in Bone Fracture Resistance. AAOS/ORS Bone Quality and Fracture Prevention Research Symposium. 2013.  Rosemont, IL, USA.

Makowski AJ, Uppuganti, S, Zein-Sabatto, A, Wadeer S; Rowland B. Yang X, Nyman JS. Transcriptional factor ATF4 regulates the Fracture Resistance of Bone. Orthopaedic Research Society. 2013, San Antonio, TX, USA.

Makowski AJ, Mahadevan-Jansen A, and  Nyman JS. A Survey of Polarization Bias Optimization Options for Confocal Raman Spectroscopy of Bone. SPIE Photonics West. 2013.  San Francisco, CA, USA.

Makowski AJ, Uppuganti, S, Nyman JS. Measuring the Fracture Toughness of Mouse Bone in American Society for Bone and Mineral Research: Annual Conference.2012 Minneapolis, MN USA: ASBMR.

Makowski AJ, Uppuganti, S, Rowland B, Merkel A, Perrien D, Sterling J, Nyman JS. TGF-β Suppression with a Neutralizing Antibody Increases Vertebral Body Strength in Female Mice in American Society for Bone and Mineral Research: Annual Conference.2012 Minneapolis, MN USA: ASBMR.

Makowski AJ, C.A. Patil, L. Gorochow, A. Mahadevan-Jansen, J.S. Nyman. Polarization Control of Raman Spectroscopy Optimizes Measures of Bone Quality in American Society for Bone and Mineral Research: Annual Conference.2011 San Diego, CA, USA: ASBMR.

Makowski AJ, J.M. Davidson, A. Mahadevan-Jansen, and E.D. Jansen. Laser Preconditioning for Wound Healing: a Raman Spectroscopy Analysis. in American Society for Laser Medicine and Surgery: Annual Conference. 2010. Phoenix, AZ, USA: ASLMS.

Nyman JS, Makowski AJ, Wadeer SA, Murry MR, Yang X. The Loss of ATF4 Reduces the Toughness of Bone in American Society for Bone and Mineral Research: Annual Conference. 2011. San Diego, CA, USA: ASBMR.

Nyman JS, Merkel J, Rowland B, Esparza J, Makowski AJ, Sterling J. The Effect of TGFβ Suppression on Bone Quality and Tumor Burden in Two Mouse Models of Multiple Myeloma in 11th International Conference on Cancer-Induced Bone Disease. 2011. Chicago, IL, USA: IBMS and CABS.

Pence I, Patil CA, Vargis E, Walsh A, Keller M, Krishnamoorthi H, Cayce J, Paras C, Makowski AJ, Bi X, Mackanos M, Jansen ED, Ellis D, Mahadevan-Jansen A. Characterizing Variability in Raman Spectra of Benign Lesions Towards Cancer Detection in Skin. in American Society for Laser Medicine and Surgery: Annual Conference. 2011. Grapevine, TX, USA: ASLMS.

 

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