Research in our laboratory covers a wide range of topics applicable to Neuroscience. Current research encompasses techniques for optimizing outcomes of peripheral nerve repair as well as studies of the pathology of muscle degeneration following peripheral nerve injury or long-term neuromuscular blockade. In addition, ongoing studies investigate the regulation of the thermoregulatory microvasculature of the digits through autonomic control of this vasculature in normal and disease conditions. From a broader perspective, our laboratory also has an interest in the autonomic control of the cardiovascular system and integration of systemic and microvascular control.

Our laboratory also trains Orthopaedic Residents in research techniques applicable a career in academic Orthopaedic Surgery. These residents are engaged in clinically relevant research and offer an opportunity to collaborate with academic physicians to better understand the perspective of our clinical colleagues. Our laboratory also teaches microsurgical technique and a variety of animal models are available for integrative physiological studies.

Stabile KJ, Odom D, Smith TL, Northam C, Whitlock PW, Smith BP, Van Dyke ME, Ferguson CM. An acellular, allograft-derived meniscus scaffold in an ovine model. Arthroscopy. 2010; 26(7):936-948.

Deal DN, Ma J, Apel P, Novak V, Carlson CS, Parker JB, Olson EJ, Rieser GR, Smith TL, Shilt JS. Effect of intra-articular pressurization associated with arthroscopy on the immature physis: investigation in an animal model. J Pediatr Orthop. 2010; 30(1):21-25.

Li Z, Smith BP, Tuohy C, Smith TL, Koman LA. Complex regional pain syndrome after hand surgery. Hand Clin. 2010; 26(2):281-289.

Nunez F, Trach S, Kislukin V, Van Dyke M, Callahan M, Smith T, Koman LA. Comparison of hemodynamic changes after hemorrhage and treatment with hyperviscous fluids [abstract]. Shock. 2010; 33(Suppl 1):16.

Li Z, Chloros GD, Smith BP, Smith TL, Koman LA. Management of upper extremity pain and vascular disorders. In: Trumble TE, Rayan GM, Budoff JE, Baratz ME, eds. Principles of hand surgery and therapy. 2nd ed. Philadelphia: Saunders Elsevier; 2010: 270-285.

Apel PJ, Crane D, Northam CN, Callahan M, Smith TL, Teasdall RD. Effect of selective sensory denervation on fracture-healing: an experimental study of rats. J Bone Joint Surg Am. 2009; 91(12):2886-2895.

Coldren FM, Palavecino EL, Levi-Polyachenko NH, Wagner WD, Smith TL, Smith BP, Webb LX, Carroll DL. Encapsulated Staphylococcus aureus strains vary in adhesiveness assessed by atomic force microscopy. J Biomed Mater Res A. 2009; 89(2):402-410.

Smith TL, Blum K, Callahan MF, DiNubile NA, Chen TJH, Waite RL. H-Wave induces arteriolar vasodilation in rat striated muscle via nitric oxide-mediated mechanisms. J Orthop Res. 2009; 27(9):1248-1251.

Sierpinski P, Garrett J, Ma J, Apel P, Smith T, Atala A. Koman A, Van Dyke M. Human hair derived keratins mediate Schwann cell behavior in vitro and facilitate rapid regeneration of peripheral nerves in vivo [abstract]. Tissue Eng Part A. 2008; 14(5):859.

Apel PJ, Garrett JP, Sierpinski P, Ma J, Atala A, Smith TL, Koman LA, Van Dyke ME. Peripheral nerve regeneration using a keratin-based scaffold: long-term functional and histological outcomes in a mouse model. J Hand Surg [Am]. 2008; 33(9):1541-1547.

Seyler TM, Smith BP, Marker DR, Ma J, Shen J, Smith TL, Mont MA, Kolaski K, Koman LA. Botulinum neurotoxin as a therapeutic modality in orthopaedic surgery: more than twenty years of experience. J Bone Joint Surg Am. 2008; 90(Suppl 4):133-145.

Brown JM, Bell TA III, Alger HM, Sawyer JK, Smith TL, Kelley K, Shah R, Wilson MD, Davis MA, Rudel LL, et al. Targeted depletion of hepatic ACAT2-driven cholesterol esterification reveals a non-biliary route for fecal neutral sterol loss. J Biol Chem. 2008; 283(16):10522-34.

Whitlock P, Seyler T, Smith T, Poehling G, Koman LA. Effect of strain on a novel cell-seeded scaffold for tendon and ligament reconstruction [abstract]. In: Program Book of the 54th Annual Meeting of the Orthopaedic Research Society; 2008 Mar 2-5; San Francisco (CA). 2008; ():1476.

Whitlock P, Poehling G, Smith T, VanDyke M, Shilt J. Development, characterization, and cell-seeding of a naturally-derived scaffold for tendon and ligament resconstruction [abstract]. In: Program Book of the 54th Annual Meeting of the Orthopaedic Research Society; 2008 Mar 2-5; San Francisco (CA). 2008; ():1481.

Sierpinski P, Garrett J, Ma J, Apel P, Klorig D, Smith T, Koman LA, Atala A, Van Dyke M. The use of keratin biomaterials derived from human hair for the promotion of rapid regeneration of peripheral nerves. Biomaterials. 2008; 29(1):118-128.

Li Z, Ma J, Apel P, Carlson CS, Smith TL, Koman LA. Brachial plexus birth palsy-associated shoulder deformity: a rat model study. J Hand Surg [Am]. 2008; 33(3):308-312.

Chloros GD, Smerlis NN, Li Z, Smith TL, Smith BP, Koman LA. Noninvasive evaluation of upper-extremity vascular perfusion. J Hand Surg [Am]. 2008; 33(4):591-600.

Mulya A, Lee J-Y, Gebre AK, Boudyguina EY, Chung S-K, Smith TL, Colvin PL, Jiang X-C, Parks JS. Initial interaction of apoA-I with ABCA1 impacts in vivo metabolic fate of nascent HDL. J Lipid Res. 2008; 49(11):2390-2401.

Delo DM, Wang Z, Shaffer R, Guan X, Neshat S, Smith T, Callahan M, Groban L, Atala A, Soker S. Effects of human amniotic fluid derived stem cells on cardiac function after myocardial infarction [abstract]. Tissue Eng Part A. 2008; 14(5):844.

Whitlock PW, Smith TL, Shilt JS, Poehling GG, Van Dyke ME. A tissue-engineered tendon scaffold [abstract]. Tissue Eng Part A. 2008; 14(5):698.

Ward WG, Smith TL, Rosencrance E, Deal DN, Dickerson E, Holsenbeck S. Soft tissue ingrowth in metal rods with varying surface textures and its clinical significance. Mater Sci Forum. 2007; 539-543():545-546.

Stabile KJ, Whitlock PW, Smith TL, VanDyke ME, Ferguson CM. A tissue engineered meniscus scaffold [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007; ():222.

Whitlock PW, Smith TL, Poehling GG, Shilt JS, Van Dyke M. A naturally derived, cytocompatible, and architecturally optimized scaffold for tendon and ligament regeneration. Biomaterials. 2007; 28(29):4321-4329.

Apel PJ, Garrett J, Sierpinski P, Ma J, Hick J, Smith TL, Koman LA, Van Dyke ME. Peripheral nerve regeneration using a keratin gel-based scaffold: long-term functional and histological outcomes in a mouse model [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007; ():364.

Lee J-Y, Badeau RM, Mulya A, Boudyguina E, Gebre AK, Smith TL, Parks JS. Functional LCAT deficiency in human apolipoprotein A-I transgenic, SR-BI knockout mice. J Lipid Res. 2007; 48(5):1052-1061.

Callahan MF, Kislukhin VK, Thuramalla NV, Krivitski NM, Smith TL. Novel technique for estimation of hemodynamic status of rats during hemorrhage and resuscitation [abstract]. FASEB J. 2007; 21(6):A1259.

Norris JA, Cabrera MN, Smith TL, Reeves SH, Koman LA. Quantifying spasticity in a clinical setting. Biomed Sci Instrum. 2007; 43():284-289.

Sierpinski PL, Garrett J, Ma J, Apel PJ, Smith T, Koman LA, Atala A, Van Dyke M. A biomaterial derived from human hair keratins can serve as a scaffold for tissue engineering in orthopaedic applications [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007; ():61.

Sierpinski PL, Apel PJ, Burnell JM, Klorig D, Smith T, Koman LA, Atala A, Van Dyke M. Keratin biomaterials made from human hair mediate Schwann and endothelial cell activity in vitro [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007; ():417.

Whitlock PW, Smith TL, Shilt JS, Poehling GG, Van Dyke ME. Development, characterization and cell-seeding of a novel biocompatible scaffold for tendon and ligament reconstruction [abstract]. FASEB J. 2007; 21(5):A268.

Gmeiner WH, Garg S, Hatcher HC, Smith TL, Bourland JD, Garg PK. MicroPET imaging to monitor tumor response to single agent and combined ionizing radiation therapy and FdUMP treatment [abstract]. J Nucl Med. 2007; 48(6 Suppl 2):83P.

Langfitt M, Webb L, Smith TL. Microvascular effects of therapeutic topical negative pressure application (TNPA) [abstract]. FASEB J. 2007; 21(5):A486.

Sierpinski P, Garrett J, Ma J, Apel P, Smith T, Atala A, Koman LA, Van Dyke M. Human hair derived keratins mediate Schwann cell behavior in vitro and facilitate rapid peripheral nerve regeneration in vivo [abstract]. FASEB J. 2007; 21(6):A1273.

Sierpinski P, Garrett J, Ma J, Apel P, Smith T, Atala A, Koman LA, Van Dyke M. Human hair derived keratins facilitate regeneration of peripheral nerves in vivo [abstract]. Tissue Eng. 2007; 13(7):1706-1707.

Ma J, Shen J, Garrett JP, Lee CA, Li Z, Elsaidi GA, Tan KH, Smith TL, Smith BP, Koman LA, et al. Gene expression of myogenic regulatory factors, nicotinic acetylcholine receptor subunits, and GAP-43 in skeletal muscle following denervation in a rat model. J Orthop Res. 2007; 25(11):1498-1505.

Whitlock PW, Knutson J, Smith TL, Van Dyke ME, Shilt JS, Koman LA, Poehling GG. Effects of mechanical stimulation on a cell-seeded scaffold developed for tendon and ligament regeneration [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007; ():391.

Ma J, Shen J, Smith BP, Ritting A, Smith TL, Koman LA. Bioprotection of tendon repair: adjunctive use of botulinum toxin A in Achilles tendon repair in the rat. J Bone Joint Surg Am. 2007; 89(10):2241-2249.

Stone AV, Ma J, Whitlock PW, Koman LA, Smith TL, Smith BP, Callahan MF. Effects of Botox and Neuronox on muscle force generation in mice. J Orthop Res. 2007; 25(12):1658-1664.

Whitlock PW, Smith TL, Shilt JS, Van Dyke ME, Poehling GG. A novel scaffold for tendon and ligament regeneration derived from human allograft tissue [abstract]. In: Transactions Online of the 6th Combined Meeting of the Orthopaedic Research Societies; 2007 Oct 20-24; Honolulu (HI). 2007; ():188.

Whitlock PW, Smith TL, Shilt JS, Poehling GG, Van Dyke ME. Development of a biocompatible scaffold for tendon and ligament regeneration [abstract]. In: Transactions Online of the 53rd Annual Meeting of the Orthopaedic Research Societies; 2007 Feb 11-14; San Diego (CA). 2007; 32():0333.

Blum K, DiNubile NA, Chen TJH, Waite RL, Martinez-Pons M, Callahan MF, Smith TL, Mengucci J, Blum SH, Meshkin B. H-wave, a nonpharmacologic alternative for the treatment of patients with chronic soft tissue inflammation and neuropathic pain: a preliminary statistical outcome study. Adv Ther. 2006; 23(3):446-455.

Buss RR, Gould TW, Ma J, Vinsant S, Prevette D, Winseck A, Toops KA, Hammaback JA, Smith TL, Oppenheim RW. Neuromuscular development in the absence of programmed cell death: phenotypic alteration of motoneurons and muscle. J Neurosci. 2006; 26(52):13413-27.

Lee CA, Ma J, Deal N, Smith BP, Koman LA, Smith TL, Shilt JS. Neuromuscular recovery after distraction osteogenesis at different frequencies in a rabbit model. J Pediatr Orthop. 2006; 26(5):628-633.

SYNOPSIS OF AREA OF INTEREST: The overall areas of interest in this laboratory are microcirculation of thermoregulation and inflammation, hemodynamics, peripheral nerve injury and repair, skeletal muscle adaptation to injury, diabetes, microsurgery, wound care, and tissue reconstruction.

DETAILED AREA OF INTEREST: Research in the Department of Orthopaedic Surgery covers many disciplines. Current projects in collaboration with the Wake Forest Institute for Regenerative Medicine include the following:

The use of tissue engineered constructs for repair of significant peripheral nerve gaps following injury. Small silastic conduits are filled with keratose gels and used to repair tibial nerve gaps in mice. These preliminary constructs result in improved nerve conduction velocity distal to the injury, increase amplitude of EMG, and improved muscle force generation with nerve stimulation. Murine models of nerve injury provide reproducible test beds for these engineered constructs.

Tissue engineered allografts for ACL, tendon, and meniscus repairs. Techniques for decellularizing and repopulating these allograft tissues are being developed to reduce immunogenicity and improve graft incorporation and remodeling by the recipient. Engineered structures then can be implanted in appropriate animal models (sheep, rabbit, mice) to evaluate in vivo incorporation.

Murine models of myocardial infarction to test stem cell therapies utilizing coronary artery ligations performed as survival surgeries in mice. These ligations produce predictable lesions of the myocardium which can subsequently be injected with myocardial progenitor cells in an effort to reduce the degree of myocardial deficits accompanying infarction. Assessment of cardiac function in the mice to determine myocardial recovery with and without therapy is performed using ventricular pressure-volume loops and ultrasound imaging.

Coming soon . .