Tessa A. Hadlock

A Polymer Foam Conduit Seeded with Schwann Cells Promotes Guided Peripheral Nerve Regeneration

Alternatives to autografts have long been sought for use in bridging neural gaps. Many entubulation materials have been studied, although with generally disappointing results in comparison with autografts. The purpose of this study was to design a more effective neural guidance conduit, to introduce Schwann cells into the conduit, and to determine regenerative capability through it in an in vivo model. A novel, fully biodegradable polymer conduit was designed and fabricated for use in peripheral nerve repair, which approximates the macro- and microarchitecture of native peripheral nerves. It comprised a series of longitudinally aligned channels, with diameters ranging from 60 to 550 microns. The lumenal surfaces promoted the adherence of Schwann cells, whose presence is known to play a key role in nerve regeneration. This unique channel architecture increased the surface area available for Schwann cell adherence up to five-fold over that available through a simple hollow conduit. The conduit was composed of a high-molecular-weight copolymer of lactic and glycolic acids (PLGA) (MW 130,000) in an 85:15 monomer ratio. A novel foam-processing technique, employing low-pressure injection molding, was used to create highly porous conduits (approximately 90% pore volume) with continuous longitudinal channels. Using this technique, conduits were constructed containing 1, 5, 16, 45, or more longitudinally aligned channels. Prior to cellular seeding of these conduits, the foams were prewet with 50% ethanol, flushed with physiologic saline, and coated with laminin solution (10 microg/mL). A Schwann cell suspension was dynamically introduced into these processed foams at a concentration of 5 X 10(5) cells/mL, using a simple bioreactor flow loop. In vivo regeneration studies were carried out in which cell-laden five-channel polymer conduits (individual channel ID 500 microm, total conduit OD 2.3 mm) were implanted across a 7-mm gap in the rat sciatic nerve (n = 4), and midgraft axonal regeneration compared with autografts (n = 6). At 6 weeks, axonal regeneration was observed in the midconduit region of all five channels in each experimental animal. The cross-sectional area comprising axons relative to the open conduit cross sectional area (mean 26.3%, SD 10. 1%) compared favorably with autografts (mean 23.8%, SD 3.6%). Our methodology can be used to create polymer foam conduits containing longitudinally aligned channels, to introduce Schwann cells into them, and to implant them into surgically created neural defects. These conduits provide an environment permissive to axonal regeneration. Furthermore, this polymer foam-processing method and unique channeled architecture allows the introduction of neurotrophic factors into the conduit in a controlled fashion. Deposition of different factors into distinct regions within the conduit may be possible to promote more precisely guided neural regeneration.

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.

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).

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.

Quantification of Functional Recovery Following Rat Sciatic Nerve Transection

Functional recovery following experimental nerve injury has been notoriously difficult to quantify precisely. The current gold standard in the rat sciatic nerve model involves analysis of footprints of the recovering animal, and computation of the sciatic function index (SFI). We performed transection injuries and measured recovery both by walking track analysis and by a newer, simpler, more quantitative test of motor recovery, the extensor postural thrust (EPT). We demonstrate a high correlation between both testing modalities and suggest a role for EPT measurements as an easier, more consistent measure of motor recovery following experimental rat sciatic nerve transection.

A Novel, Biodegradable Polymer Conduit Delivers Neurotrophins and Promotes Nerve Regeneration†

Objective/Hypothesis: A wide variety of substances have been shown to promote neuritic extension after nerve injury. An obstacle to achieving the maximal benefit from these substances has been the difficulty in effectively delivering the substances over a protracted time course that promotes maximal, directed growth. In this study the delivery of a growth‐promoting substance through a biodegradable conduit, using materials originally designed for drug delivery applications, was hypothesized to promote more robust neural regeneration than through conduits lacking the substance. The objectives of this study were to create a growth factor‐loaded biodegradable nerve guidance conduit, and to assess in vivo nerve regeneration through the conduit compared with that through conduits lacking the substance.

Multimodality Approach to Management of the Paralyzed Face

Objectives: Despite the ability of facial reanimation techniques to introduce meaningful movement to the paralyzed face, dynamic methods do not address all zones of the face. Our objective was to retrospectively review outcomes after multimodality management of the patient with facial paralysis, to describe several novel surgical methods that introduce subtle improvements in static facial balance, and to present an algorithm for comprehensive management of the paralyzed face.

Validation of the Synkinesis Assessment Questionnaire

Objective: To validate the Synkinesis Assessment Questionnaire (SAQ), a newly developed patient‐graded instrument to evaluate facial synkinesis.

Comprehensive Facial Rehabilitation Improves Function in People With Facial Paralysis: A 5-Year Experience at the Massachusetts Eye and Ear Infirmary

Background The Facial Grading Scale (FGS) is a quantitative instrument used to evaluate facial function after facial nerve injury. However, quantitative improvements in function after facial rehabilitation in people with chronic facial paralysis have not been shown. Objective The objectives of this study were to use the FGS in a large series of consecutive subjects with facial paralysis to quantitatively evaluate improvements in facial function after facial nerve rehabilitation and to describe the management of chronic facial paralysis. Design The study was a retrospective review. Methods A total of 303 individuals with facial paralysis were evaluated by 1 physical therapist at a tertiary care facial nerve center during a 5-year period. Facial rehabilitation included education, neuromuscular training, massage, meditation-relaxation, and an individualized home program. After 2 months of home exercises, the participants were re-evaluated, and the home program was tailored as necessary. All participants were evaluated with the FGS before the initiation of facial rehabilitation, and 160 participants were re-evaluated after receiving treatment. All participants underwent the initial evaluation at least 4 months after the onset of facial paralysis; for 49 participants, the evaluation took place more than 3 years after onset. Results Statistically significant increases in FGS scores were seen after treatment (P<.001, t test). The average initial score was 56 (SD=21, range=13–98), and the average score after treatment was 70 (SD=18, range=25–100). Limitations A limitation of this study was that evaluations were performed by only 1 therapist. Conclusions For 160 patients with facial paralysis, statistically significant improvements after facial rehabilitation were shown; the improvements appeared to be long lasting with continued treatment. The improvements in the FGS scores indicated that patients can successfully manage symptoms with rehabilitation and underscored the importance of specialized therapy in the management of facial paralysis.

Botulinum Toxin and Quality of Life in Patients With Facial Paralysis

OBJECTIVES To examine the effect botulinum toxin, a potent neurotoxin that causes temporary paralysis of hyperkinetic musculature, has on the quality of life (QOL) in the patient with facial paralysis. We surveyed patients with facial paralysis, using the previously validated Facial Clinimetric Evaluation QOL instrument, before and then again after therapeutic administration of botulinum toxin for the management of their facial hyperkinesis, and performed pair-wise comparisons to determine the effect on patient QOL. DESIGN Prospective clinical study at an outpatient facial nerve center. RESULTS The overall Facial Clinimetric Evaluation score improved from a mean (SD) of 51.7 (20.9) in the pretreatment group to 63.7 (17.8) in the posttreatment group (P < .05). Statistically significant improvements were noted in all subdomain scores, including Facial Movement, Facial Comfort, Oral Function, Eye Comfort, Lacrimal Control, and Social Function (P < .05 for all comparisons). CONCLUSIONS Botulinum toxin has a well-established objective benefit in the control of facial hyperkinesis in patients with facial nerve disorders. This study establishes the associated QOL benefit and reaffirms its important role in the multimodality management of patients with facial nerve disorders.