Dr. Ho's current research interests as a faculty member in the Division of Biomaterials and Bioengineering, UCSF are in two different, but overlapping areas: 1) Epigenetic factors and form – function relationships; 2) Regeneration of soft-hard tissue attachment.
Functional efficiency of most organs is broadly governed by two factors; genetic and epigenetic. In my laboratory we are currently studying the effect of two epigenetic factors: load and disease; and load plus disease on the bone-ligament-tooth complex using in vivo models. Furthermore, the observed load-based nanoscale events are mimicked by programming them as functional cues on synthetic substrates to promote tissue specific cell differentiation and regeneration for soft-hard tissue functional attachment.
1) Epigenetic factors influence on form-function relationship
The bone-ligament-tooth complex is an excellent bioengineered system in which several natural interfaces between soft-hard or hard-hard tissues provide biomechanical efficiency of the fibrous joint. However, functional efficiency can be impaired if any one of the interfaces and/or tissues adapt to epigenetic factors: load and disease. In both diseased and/or load-based organs, resorption or formation related biomineralization events affect the interfaces. A systematic approach to investigate mineral resorption and formation related phenomena involves harnessing principles of mechanics, materials science, and mechanobiology at organ, tissue and cell-levels in the bone-tooth fibrous joint. Models include ligature induced periodontitis to investigate bacterial induced mineral formation and resorption, and functional load modulation by food consistency and/or imposition of unidirectional vectors to investigate force (magnitude and direction of load) induced mineral formation and resorption. This excellent model i.e. the bone-ligament-tooth complex can elucidate a wide spectrum of clinical scenarios, from bony spurs related to enthesopathies to tissue regeneration related to distraction osteogenesis in both musculoskeletal, and oral and craniofacial systems.
2) Regeneration of soft-hard tissue attachment
The soft-hard tissue interfaces in the bone-ligament-tooth complex parallel several other similar interfaces in the musculoskeletal system including tendon-bone and ligament-bone interfaces. Challenges to date in oral and musculoskeletal systems include “functional regeneration” of “soft- and hard-tissue interfaces” that are seminal to the load-bearing nature of fibrous and diarthroidal joints. Parameters investigated under item 1 are programmed as “functional cues” on synthetic substrates to promote tissue regeneration/attachment specific to soft-hard tissue interfaces. Regeneration events include tissue-specific cell differentiation and basic constituents i.e. collagen, noncollagenous proteins, and apatite formation necessary to provide functional integrity for a load bearing interface.
The impending challenges in advancement of health care can be best addressed when fundamental science is synchronized with collaborations across several disciplines and clinical needs. Hence, the research team consists of scientists/clinicians within the Bay Area; Stanford Synchrotron Radiation Lightsource (SSRL), Stanford Linear Accelerator Center, and the Molecular Foundry, Lawrence Berkeley National Laboratory (LBL). Several interdisciplinary methods are implemented routinely to investigate the aforementioned research topics. These include macroscale in situ loading devices coupled to high resolution X-ray computed tomography, high resolution spectroscopy techniques for early and late stage chemical markers, micro- and nano-indentation to identify tissue differences and/or tissue heterogeneity through site-specificity, immunohistochemistry, fluorescence microscopy, dynamic histomorphometry and in situ hybridization. Other techniques include high resolution microscopy using atomic force, transmission X-ray, scanning electron microscopy techniques for micro and nano-scale analysis under dry and wet conditions. Extension of laboratory facilities within the Division of Biomaterials and Bioengineering is made possible through user proposals at the Molecular Foundry of LBL, and SSRL.
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