The focus of Dr. Mark R. Appleford's current research is to examine bone cell interactions with biomaterials and to study the pathways of cell differentiation into mature tissues.
To clarify cell-biomaterial interactions, he examines the integrin receptor activity of cells during their first contact with a biomaterial. Sub-cellular signaling pathways have been identified to track key players such as the stress activated protein kinases (SAPK), viability markers such as P38 and differentiation gene transcription factor RUNX2. By following pathways from outside the cell, through internal protein signaling and finally to the production of specific proteins by the cell, we can help explain the mechanisms responsible for implant rejection or successful long-term integration. Most research in this field has been performed with experiments of 2D cell monolayers. Our laboratory has developed a variety of techniques to measure these signals within 3D scaffolds to better understand the mechanisms of cell behavior. The laboratory also explores the tissue-level formation of new bone through the use of bioreactor tissue engineering. Fluid perfusion chambers have been used to grow volumes of bone tissue in the laboratory for up to three months. By studying the morphology of the new tissue we can help refine ideal culture conditions for replacement grafts while identifying the precise fluid shear mechanical forces associated with differentiation pathways.
In addition to these basic science approaches, the laboratory works on the large scale reconstruction of bone and cartilage tissue using natural ceramic scaffolds. Calcium phosphate foams serve as a template for bone bridging of large segmental defects in the cranium, femur and tibia. The approach of this research has been to bridge a large defect for early integration while still allowing for natural blood vessel and bone formation that ultimately replaces the scaffold within a year.
P Konofaos, D Petersen, JA Jennings, RA Smith, H Doty, BT Reves, T Guda, M Appleford, J Bumgardner, R Wallace. Evaluation of Amniotic Multipotential Tissue Matrix to Augment Healing of Demineralized Bone Matrix in an Animal Calvarial Model. Journal of Craniofacial Surgery 26 (4), 1408-1412, 2015.
X Yang, C Gandhi, MDM Rahman, M Appleford, LW Sun, X Wang. Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption. Calcified tissue international 97 (6), 592-601, 2016.
X Yang, AJ Mostafa, M Appleford, LW Sun, X Wang. Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo. Calcified tissue international, 99 (4) 373-383, 2016.
Pilia M, Murray M, Guda T, Heckman M, Appleford M. Orthopedics “Pretensioning of Soft Tissue Grafts in Anterior Cruciate Ligament Reconstruction.” 2015 Jul 1;38(7):e582-7. doi: 10.3928/01477447-20150701-55. PMID:26186319
Rathbone CR, Guda T, Singleton BM, Oh DS, Appleford MR, Ong JL, Wenke “Effect of cell-seeded hydroxyapatite scaffolds on rabbit radius bone regeneration” JC. J Biomed Mater Res A. 2014 May;102(5):1458-66. doi: 10.1002/jbm.a.34834. Epub 2013 Jun 22. PMID: 23776110
M. Pilia, T. Guda, B. Pollot, V. Aguero, M. R. Appleford, “Local microarchitecture affects mechanical properties of deposited extracellular matrix for osteonal regeneration", Materials Science and Engineering C, 2014, Vol. 35, pp:122-133.
T. Guda, J.A. Walker, J. Hernandez, B. Singleton, M.R. Appleford, S. Oh, J.L. Ong, J.C. Wenke, “Hydroxyapatite scaffold pore architecture effects in large bone defects in vivo”, Journal of Biomaterials Applications, 2014, Vol. 28, Iss.7, pp:1016-1027.
C.R. Rathbone, T. Guda, B. Singleton, S. Oh, M.R. Appleford, J.L. Ong, J.C. Wenke, “Effect of hydroxyapatite scaffolds seeded with cells on in vivo bone regeneration ”, Journal of Biomedical Materials Research A, 2014, Vol. 102, Iss. 5, pp:1458–1466
CM Agrawal, JL Ong, MR Appleford, G Mani. Introduction to Biomaterials: Cambridge University Press 2014.
X Yang, C Gandhi, RM Mizanur, MR Appleford, LW Sun, X Wang. Aging Effects of Advanced Glycation End Products on Osteoclast Resorption on Human Bone JOURNAL OF BONE AND MINERAL RESEARCH 29, S424-S424. 2014.