Our lab aims to bridge the gap between biomedical discoveries in the lab and clinical application. We emphasize translation of our work. From idea origination throughout design, we keep clinical translation in mind. We aim to re-establish function in disease or damaged organs and tissues by utilizing the principles of tissue mechanics and by replicating native tissue structure through recreating developmental cues in the lab.
Recreating Natural Cues to Engineer Functional Tissue Replacements
Tissue engineering efforts have spanned decades, yet difficulty remains in creating tissues with enough functionality for clinical use. One major reason for the lack of functionality in engineered tissues is the limited number of natural cues applied during construct generation. Our lab is developing methods to recreate multiple natural developmental cues simultaneously during engineered tissue formation in order to create more functional tissue replacements. We have developed methods for skeletal muscle, cardiac muscle, and most recently vascular tissue. To recreate these natural cues, we utilize and replicate in the lab the principles of cellular biomechanics, topography, and most importantly proper tissue architecture.
Relevant publications:
Tissue engineering efforts have spanned decades, yet difficulty remains in creating tissues with enough functionality for clinical use. One major reason for the lack of functionality in engineered tissues is the limited number of natural cues applied during construct generation. Our lab is developing methods to recreate multiple natural developmental cues simultaneously during engineered tissue formation in order to create more functional tissue replacements. We have developed methods for skeletal muscle, cardiac muscle, and most recently vascular tissue. To recreate these natural cues, we utilize and replicate in the lab the principles of cellular biomechanics, topography, and most importantly proper tissue architecture.
Relevant publications:
- Pinnock CB, Meier EM, Joshi NN, Wu B, Lam MT. Customizable engineered blood vessels using 3D printed inserts. Methods 2015 pii: S1046-2023(15)30184-5.
- Raghavan S, Lam MT, Foster LL, Gilmont RR, Somara S, Takayama S, Bitar KN. Bioengineered three-dimensional physiological model of colonic longitudinal smooth muscle in vitro. Tissue Eng Part C Methods. 2010;16(5):999-1009.
- Lam MT, Huang YC, Birla RK, Takayama S. Microfeature guided skeletal muscle tissue engineering for highly organized 3-dimensional free-standing constructs. Biomaterials. 2009;30(6):1150-5.
- Lam MT, Clem WC, Takayama S. Reversible on-demand cell alignment using reconfigurable microtopography. Biomaterials. 2008;29(11):1705-12.
- Lam MT, Sim S, Zhu X, Takayama S. The effect of continuous wavy micropatterns on silicone substrates on the alignment of skeletal muscle myoblasts and myotubes. Biomaterials. 2006;27(24):4340-7.
Stem Cell Patch Development
The general mode of delivery of stem cells to a patient is via injection. However, it is well known that stem cells tend to dissipate and die when delivered in this manner. By delivering stem cells on a patch, the stem cells can be kept locally to the wound and the biomaterial patch can sustain prolonged survival and in some cases increase cell proliferation. In applying a stem cell patch system to skin wounds, we found that stem cells survived longer and increased in proliferation, resulting in significantly lower amounts of scar tissue. Our present study involves development of a stem cell patch system for myocardial infarction application, by tailoring the patch system to the unique tissue and healing mechanics of the heart.
Relevant publications:
The general mode of delivery of stem cells to a patient is via injection. However, it is well known that stem cells tend to dissipate and die when delivered in this manner. By delivering stem cells on a patch, the stem cells can be kept locally to the wound and the biomaterial patch can sustain prolonged survival and in some cases increase cell proliferation. In applying a stem cell patch system to skin wounds, we found that stem cells survived longer and increased in proliferation, resulting in significantly lower amounts of scar tissue. Our present study involves development of a stem cell patch system for myocardial infarction application, by tailoring the patch system to the unique tissue and healing mechanics of the heart.
Relevant publications:
- Lam MT, Nauta AC, Meyer NP, Wu JC, Longaker MT. Effective delivery of stem cells using an extracellular matrix patch results in increased cell survival and proliferation and reduced scarring in skin wound healing. Tissue Eng Part A. 2013;19(5-6):1-10.
- Lam MT, Wu JC. Biomaterials Applications in Cardiovascular Tissue Repair and Regeneration. Expert Review of Cardiovascular Therapy. 2012;10(8):1039-49.
- Lam MT, Longaker MT. Comparison of several attachment methods for human iPS, embryonic and adipose-derived stem cells for tissue engineering. J Tissue Eng Regen Med. 2012;6 Suppl 3:s80-6.
Mechanically-driven Stem Cell Differentiation
Many tissues depend on mechanical cues during development to mature into the correct phenotype. Using a custom built mechanical stimulation device, we study the effects of mechanical strain on various stem cell types, and use these findings to drive stem cell differentiation towards mechano-sensitive cell types. This type of intervention and differentiation can produce cell sources for mechanically inclined tissue types. This is especially important for tissues where cell population is low and human cell sources are limited. Such tissues that we study are the knee meniscus and cardiac tissues.
Relevant publications:
Many tissues depend on mechanical cues during development to mature into the correct phenotype. Using a custom built mechanical stimulation device, we study the effects of mechanical strain on various stem cell types, and use these findings to drive stem cell differentiation towards mechano-sensitive cell types. This type of intervention and differentiation can produce cell sources for mechanically inclined tissue types. This is especially important for tissues where cell population is low and human cell sources are limited. Such tissues that we study are the knee meniscus and cardiac tissues.
Relevant publications:
- Meier EM, Wu B, Siddiqui A, Tepper D, Longaker MT, Lam MT. Mechanical stretch drives adipose stem cell differentiation towards a meniscus phenotype. In revision.
- Hammerick KE, Huang Z, Sun N, Lam MT, Prinz FB, Wu JC, Commons GW, Longaker MT. Elastic properties of induced pluripotent stem cells. Tissue Eng Part A. 2011;17(3-4):495-502
