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Biomedical subjects

Tessa Hadlock

Publications and source records attributed to Tessa Hadlock.

10 recordsLinked to original sources

Successful myoblast transplantation in rat tongue reconstruction.

BACKGROUND: Controversy exists regarding the success of myoblast transplantation. The purpose of this study was to determine the survival of transplanted myoblasts in a rat tongue reconstruction model by using fluorescently labeled myoblasts and surgical stains to mark the location of the pocket into which transplanted cells were delivered. We evaluated tongue histology after myoblast transplantation under the hypothesis that myoblast transplantation will promote muscle regeneration and result in minimal scar tissue formation. METHODS: Sterile solutions of 1:10 India ink, 1% methylene blue, and 1% crystal violet were applied to the inner lining of a left-sided mucosa-sparing hemiglossectomy pocket. After air-drying, the hemiglossectomy defect was filled with collagen gel and closed. The tongues were evaluated histologically at 6 weeks. Next, myoblasts were cultured and labeled with three commercially available fluorescent dyes, 5-chloromethyl-fluorescein diacetate (CMFDA), chloromethylbenzamido (CM-DiI), and fluorescently labeled microspheres (FLMs), to determine which would optimally label myoblasts in a tongue reconstruction model. Next, Lewis rats underwent left hemiglossectomy, and the created pockets were coated with 1:10 India ink. Control animals received collagen gel alone, whereas experimental animals received labeled myoblast/collagen constructs into the tongue defect. Tongues were harvested at intervals to determine the presence of labeled fluorescent cells, the relative numbers of viable myoblasts, and the degree of scarring. RESULTS: India ink coating of the hemiglossectomy pocket caused minimal inflammation and lasted longer than the other tested dyes. CMFDA and FLMs both successfully label myoblasts for transplantation. In vivo, donor cells were observed in all specimens at week 0 with increasing numbers of cells and muscle formation, determined by desmin immunofluorescence, after 6 weeks. There was less scar tissue contracture in the experimental group and a significant increase in the amount of desmin-stained muscle in the surgical defect. CONCLUSIONS: India ink is an appropriate vehicle for intra-operative marking of a hemiglossectomy cavity. The introduction of myoblast/collagen constructs into the rat hemiglossectomy defect increases the amount of regenerated muscle, results in less scar contracture, and may increase meaningful tongue function.

Animals↗

Biologically inspired approaches to drug delivery for nerve regeneration.

As the biological processes governing nerve regeneration have become elucidated over the past decades, interest has developed in manipulating these processes to improve nerve regeneration. Drug delivery to the regenerating nerve has the potential for major clinical applications in neurodegenerative diseases, spinal cord injury and peripheral nerve injury or sacrifice. This article reviews the evolution of the field of drug delivery to the regenerating nerve, from simple local applications of neurotrophic agents in solution and osmotic pump delivery, to the existing approaches involving novel biomaterials and genetically manipulated cell populations. A discussion of the various known nerve growth-promoting agents, and the chemical considerations involved in their delivery, is included. A perspective on the role of tissue engineering approaches for nerve regeneration in the future is offered.

Animals↗

Choosing the correct functional assay: a comprehensive assessment of functional tests in the rat.

While there are several ways to quantify peripheral nerve regeneration; the true measure of successful outcome is functional recovery. Functional tests are relatively easily conducted in human subjects; however it is more difficult in a laboratory animal. The laboratory rat is an excellent animal model of peripheral nerve injury and has been used extensively in the field of peripheral nerve research. Due to the intense interest in the rat as an experimental model, functional assays have been reported. In an effort to provide a resource to which investigators can refer when considering the most appropriate functional assay for a given experiment, the authors have compiled and tabulated the available functional tests applicable to various models of rat nerve injury.

Animals↗

Success of multiple, sequential, free tissue transfers to the head and neck.

INTRODUCTION: Free tissue transfer has become the primary reconstructive modality for significant ablative defects in the head and neck. The overall success rate is high, approaching 95% in most centers. The success rate of multiple sequential free flaps has been thought to be lower, based on the absence of optimal vessel availability and the presence of significant scar tissue in the previously operated patient. We evaluated a series of patients who underwent multiple free flaps at different time points to determine the overall success rate and to identify pitfalls encountered in this population. METHODS: Retrospective review, tertiary care medical center. RESULTS: From 1995 to 2002, 377 free flaps were performed by our reconstructive service. Of this group, 36 underwent multiple free flaps at different time points. Thirty-two had two flaps, and four had three flaps. Reasons for performing sequential free flap procedures were as follows: recurrent disease/new primary (18), need for further augmentation (10), failed previous flap (6), delayed mandibular reconstruction after plate fracture (2), mandibular osteoradionecrosis (3), and delayed pharyngoesophageal stenosis (1). The overall failure rate on the second and third flap was 2 of 32 and 0 of 4, respectively, with an overall success rate of 94%. CONCLUSION: Multiple, sequential, free tissue transfer for reconstruction of head and neck defects is a safe and reliable procedure with success rates equal to that in patients undergoing initial free flap reconstruction. Careful preoperative planning can result in optimal outcomes even in this difficult patient population.

Adult↗

Effects of aspirin and low-dose heparin in head and neck reconstruction using microvascular free flaps.

OBJECTIVE: The success of microvascular free-tissue transfer to the head and neck has been greatly increased secondary to increased experience, yet postoperative anticoagulation continues to be routinely used to prevent pedicle thrombosis. However, there is currently no consensus as to what the ideal regimen, if any, is recommended for postoperative anticoagulation. This study reviews the outcome and incidence of perioperative complications in patients undergoing free flaps for head and neck reconstruction, using a simple postoperative anticoagulation regimen of aspirin and subcutaneous heparin (SQH). DESIGN: Retrospective chart review. METHODS: With institutional review board approval, the charts of 261 patients undergoing free flap reconstruction from January 2000 to January 2004 were retrospectively reviewed. Patients who received a standard postoperative anticoagulation regimen of SQH (5000 U SC bid) and aspirin (325 mg PO qd) were included in the study (216 patients). Charts were reviewed for postoperative complications, specifically for free flap failure, vascular compromise (arterial insufficiency/venous congestion), and hematoma. RESULTS: There were six flap failures (2.8%), resulting in an overall free flap survival rate of 97.2%. There were six patients with venous congestion of the flap that required neck exploration (2.8%), and 12 patients with postoperative hematoma (5.6%), requiring surgical intervention. CONCLUSION: The free flap survival rate in patients undergoing head and neck reconstruction using this simple anticoagulation regimen of aspirin and SQH appears to be equivalent to the free flap survival rate in patients using other anticoagulation agents. In addition, aspirin and SQH do not increase the incidence of postoperative hematoma when compared with the other anticoagulation agents. Therefore, aspirin and SQH appear to be reliable postoperative anticoagulation agents for patients undergoing head and neck reconstruction using free flaps.

Adolescent↗

Manufacture of porous polymer nerve conduits by a novel low-pressure injection molding process.

A method to fabricate porous, biodegradable conduits using a combined injection molding, thermally induced phase transition technique was developed which produced conduits with dimensionally toleranced, longitudinally aligned channels. The geometry of the channels was designed to approximate the architecture of peripheral nerves and to support the monolayer adherence of physiologically relevant numbers of Schwann cells. The channel configuration could be varied from a single 1.35 mm diameter channel up to 100 0.08 mm diameter channels. A conduit with 100 channels has approximately 12.5 times the lumenal surface area of a single channel conduit and supports the adherence of five times the number of Schwann cells in the native peripheral nerve. In this study, poly(DL-lactide-co-glycolide) (DL-PLGA) was dissolved in acetic acid and injected into a cold mold which induced solid-liquid phase separation and, ultimately, solidification of the polymer solution. The acetic acid was removed by sublimation and the resulting foam had a macrostructure of high anisotropy. Semi-permeable skins formed on the outer and lumen diameters of the conduit as a consequence of rapid quenching. Macropores were organized into bundles of channels, up to 20 microm wide, in the DL-PLGA matrix and represented remnants of acetic acid that crystallized during solidification.

Animals↗

Tissue engineered muscle implantation for tongue reconstruction: a preliminary report.

OBJECTIVES/HYPOTHESIS: Because current tongue reconstructive methods introduce adynamic, variably sensate tissue into the mouth, the critical functions of the tongue in articulation and deglutition may be compromised. The objective of this work was to introduce a combination of myoblasts and scaffolding material into rat hemiglossectomy defects and to examine the extent of neomuscle formation in the reconstructed area, under the hypothesis that the presence of myoblasts leads to formation of new muscle. STUDY DESIGN: Randomized, prospective animal study. METHODS: Myoblasts were harvested from neonatal Lewis rats, and a growth factor enriched collagen gel was prepared. Syngeneic adult animals received either hemiglossectomy alone or reconstruction with one of four experimental reconstructive preparations: collagen gel alone, collagen gel with suspended myoblasts, the gel-cell combination in undifferentiated muscle construct form by way of tissue culture for 7 days in a preformed mold, or differentiated constructs, cultured in myoblast fusion medium. After 6 or 16 weeks, animal weight gain was recorded, animals were killed, and the tongues harvested. The tissue was examined histologically, and quality of the muscular regenerate was rated on a scale according to predefined criteria. RESULTS: Animals in all groups gained weight appropriately. In groups receiving hemiglossectomy alone or acellular (gel only) reconstruction, there was significant scarring and lack of neomuscle formation. In groups receiving myoblast transplantation, either by way of gel suspension or in the form of undifferentiated or differentiated constructs, muscle quality was superior to controls. CONCLUSIONS: Myoblast transplantation into hemiglossectomy defects appears to lead to new muscle formation and does not inhibit normal weight gain in animals after tongue implantation.

Animals↗

Muscle tissue engineering for partial glossectomy defects.

BACKGROUND: Tongue reconstruction represents a difficult reconstructive problem, based on the tongue's complex multimodality function. Existing methods of tongue reconstruction often result in significant deficits in speech and deglutition. A functional neotongue requires adequate soft tissue bulk and restoration of coordinated muscle function. Tissue engineering, a scientific approach that allows introduction of isolated cell populations of interest within 3-dimensional polymer scaffolds to create new tissue, may allow the generation of more highly functional tissue in tongue reconstruction. OBJECTIVES: To apply muscle-tissue engineering techniques in the reconstruction of partial glossectomy defects in rats, and to compare the gross and histological nature of tissue found after reconstruction of the hemiglossectomy defect with acellular vs tissue-engineered composite material. MATERIALS AND METHODS: Thirty mature Lewis rats underwent a left-sided mucosa-sparing partial glossectomy. The defects were then filled with 1 of the following 3 substances: isotonic sodium chloride solution, a collagen-rich hydrogel, or hydrogel containing a suspension of neonatal myoblasts from syngeneic rats. The animals were killed after 6 weeks and the tongues were harvested. The control and operated-on tongue halves were evaluated for weight differences and histological features. RESULTS: The group receiving the hydrogel-myoblast composite injections demonstrated a statistically significant increase in tongue weight of the operated-on side compared with the control side. In contrast, the isotonic sodium chloride solution and hydrogel groups demonstrated loss of tongue weight. These findings correlated with the results of the histological evaluation. Hemitongues from the composite group demonstrated formation of new tissue with areas of musclelike tissue extending from islands of residual hydrogel, and we found evidence of neovascularization and possible neurotization. In contrast, the isotonic sodium chloride solution group exhibited dense fibrous scar with loss of muscle architecture and dramatic loss of tongue volume. The hydrogel group demonstrated preservation of tongue volume with persistent islands of gel, but no clear evidence of new tissue formation. CONCLUSIONS: The introduction of a hydrogel into the rat hemiglossectomy pocket appears to promote volume preservation and/or muscle regeneration. The addition of myoblasts suspended in collagen gel supports the development of new tissue that preserves weight and volume after hemiglossectomy and may possess muscle properties similar to the tissue desired. This tissue-engineering approach represents a promising new strategy in tongue reconstruction and merits further investigation into the possible functional advantages it offers compared with current techniques.

Animals↗

Baiting the cross-face nerve graft with temporary hypoglossal hookup.

BACKGROUND: Cross-face nerve grafting yields inconsistent neural regeneration, and methods that promote more robust axonal traversing of the graft would expand the indications for this procedure. OBJECTIVE: To test the hypothesis that hooking a cross-face nerve graft distally to a source of denervated muscle, rather than leaving it in the subcutaneous space, would positively affect neural ingrowth across the graft, based on elaboration of neurotrophins from the musculature. METHODS: Twenty-four rats underwent cross-face nerve grafting in which the right facial nerve buccal branch was transected and coapted to the graft. The graft was placed across the neck and into the left side of the face. The distal end of the graft was placed either in the left subcutaneous space, coapted to the marginal mandibular branch of the left facial nerve, or coapted to the distal stump of the transected left hypoglossal nerve. Eight control animals underwent right buccal branch transection and placement of a cross-face nerve graft without any proximal and distal hookup. After 12 weeks, all experimental groups underwent hookup of the distal nerve graft to the left facial nerve buccal branch. Vibrissal function was assessed during the ensuing 12 weeks, and then the graft was harvested for histomorphometric analysis. RESULTS: After 12 weeks, there was a significant difference in axon counts between the group coapted distally to the tongue (hypoglossal hookup) and that coapted to the facial musculature (marginal hookup). Twelve weeks later, after distal cross-face nerve graft hookup, this difference was not statistically significant, although the hypoglossally baited group demonstrated statistically significantly greater fiber maturity. Recovery of vibrissal movement did not differ among treatment groups. CONCLUSION: Baiting the cross-face nerve graft via temporary hookup to the distal hypoglossal nerve and tongue musculature appears to improve nerve ingrowth through a nerve graft across the face, although a corresponding improvement in facial muscle function was not observed.

Animals↗