Brooke R. Seckel

Nerve regeneration through synthetic biodegradable nerve guides: regulation by the target organ.

The successful regeneration of a multifascicular, complete peripheral nerve through a tubular synthetic biodegradable nerve guide across a gap of 10 mm in the rat sciatic nerve is reported. The importance of the distal nerve as a source of target-derived neuronotrophic factors necessary for the successful regeneration of the proximal regenerating nerve is emphasized. A simplified research model for further investigation into and manipulation of the biological processes of nerve regeneration is described. The potential clinical utilization of this model in the management of peripheral nerve injuries and, ultimately, central nervous system lesions is mentioned.

Acidic Fibroblast Growth Factor Enhances Peripheral Nerve Regeneration in Vivo

When added to a collagen-filled nerve guide, purified acidic fibroblast growth factor (aFGF) increased the number of myelinated axons that regenerated across a 5-mm nerve gap distance. In addition, a greater number of primary sensory and motor neurons extended axons through the nerve guide in animals treated with aFGF. Thus the effect of aFGF on peripheral nerve regeneration is not simply an increase in axonal branching within the nerve guide tube. This is the first highly purified growth factor since nerve growth factor that has been shown to promote nerve regeneration in vivo. This experimental model provides a convenient and quantitative means to assess the effects of putative neuronotropic factors on peripheral nerve regeneration in vivo.

Target-specific nerve regeneration through a nerve guide in the rat.

&NA; Nerve regeneration across a gap in peripheral nerve has been achieved through various nonneural nerve guides in both lower and primate species. This technique can only be useful if the regenerated nerve cable grows specifically to and reinnervates the appropriate distal target. In this study, the proximal peroneal fascicle of rat sciatic nerve was inserted into the proximal limb of a Y‐shaped nerve guide. Distal peroneal and tibial fascicles were placed within the two distal limbs of the same Y. The proximal peroneal nerve grew preferentially by a 2:1 ratio to the appropriate distal peroneal fascicle suggesting that target‐specific reinnervation is possible through a nerve guide.

Hyaluronic acid enhances peripheral nerve regeneration in vivo

Hyaluronic acid has been shown to enhance peripheral nerve regeneration in vitro. It has been proposed that, during the fibrin matrix phase of regeneration, hyaluronic acid organizes the extracellular matrix into a hydrated open lattice, thereby facilitating migration of the regenerating axons. Hyaluronic acid solutions and saline control solutions were injected into a nerve guide spanning a transected gap in the sciatic nerve of Sprague‐Dawley rats (five in each group). Nerve conduction velocities were measured at 4 weeks by electromyography (EMG) before sacrifice of the animals. These studies demonstrated increased conduction velocities in the hyaluronic acid group compared with control animals (P = 0.006). After the animals were sacrificed, regenerated axon cables were quantified histologically, and axon branching was delineated by retrograde tracer analysis. In addition, the hyaluronic acid group showed an increase in myelinated axon counts at 4 weeks (P = 0.03). An increase in retrograde flow was demonstrated in the hyaluronic acid groups compared with animals receiving saline solution.

Immunocytochemistry of skeletal muscle basal lamina grafts in nerve regeneration.

The influence on nerve regeneration of the extracellular matrix glycoprotein laminin was studied after sciatic nerve transection in 90 outbred Sprague-Dawley rats. Nerve regeneration through basal lamina grafts was comparable with regeneration through traditional nerve grafts across gaps up to 2.0 cm in length. True axonal regeneration rather than axonal branching was demonstrated by retrograde horseradish peroxidase labeling of nerve cables. Pretreatment of basal lamina grafts with antilaminin antibodies reduced the total number of regenerated axons by 90 percent with a significant decrease of nerve conduction velocity and a significant impairment of walking track patterns. The basement membrane glycoprotein laminin serves a critical role in the regeneration of peripheral nerves through basal lamina grafts.

Single-dose electron beam irradiation in treatment and prevention of keloids and hypertrophic scars

Low megavolt electron beam irradiation was used on 354 sites in 199 patients at the Lahey Clinic either for palliation of symptomatic hypertrophic scars or as post-operative irradiation in an attempt to prevent formation or recurrence of hypertrophic scars. Electron energies used ranged from 1.5 to 3.5 MeV. The median age of the 59 male patients was 22 years and of the 140 female patients, 35 years. All patients had at least one follow-up visit, and the median follow-up was 35 months. Of the 294 sites treated for the first time, 272 (93%) were irradiated with a single fraction with a skin dose ranging from 2 to 20 Gy. Of the 85 sites in 63 patients without excision of symptomatic hypertrophic scars, single-dose electron beam irradiation was of clinically significant value in only 41 sites (48%). No patients have been treated without surgical excision since 1973. Because of a history of formation of hypertrophic scars elsewhere in the body, 13 patients with 19 incisions were treated prophylactically after operation for other diseases. All sites were irradiated with single doses ranging from 8 to 20 Gy, and hypertrophic scars did not subsequently develop in any patient. Altogether, 119 patients with 174 sites were irradiated after surgical excision of hypertrophic scars to prevent recurrence; 168 sites (97%) received single-fraction irradiation, and 161 received a dose of 8 Gy or greater, up to 15 Gy. No statistically significant differences were observed in complete success rates, ranging from 82 to 90% with doses of 9 Gy or greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascularized versus nonvascularized nerve grafts: an experimental structural comparison.

This study compared the success of nerve regeneration through conventional nonvascularized and vascularized nerve grafts in the sciatic nerve of rats. The number or size of regenerated axons between the two grafts was not significantly different. In addition, the ratio of axonal diameter to total diameter of the nerve, a measurement linearly related to conduction velocity, was not significantly different in the two groups. Thicker myelin sheaths were found around axons in the nonvascularized nerve grafts.

Sensory Reinnervation in Microsurgical Reconstruction of the Heel

Six sensory reinnervation techniques were carried out in 10 patients who underwent reconstruction of the weight‐bearing surface of the heel by microsurgical free‐tissue transfer. The techniques include the use of (1) neurovascular island flaps, (2) neurosensory flaps, (3) sensory nerve grafts to skin flaps, (4) coaptation of the sensory nerve to the motor nerve of the muscle flaps, (5) direct sensory nerve transfer, and (6) sensory nerve graft transfer. In all patients, some sensation developed, characterized by sensation to light touch, to dull objects, to pinprick, to pain, and to tickling. Three patients developed the ability to distinguish sharp from dull objects and the sensation of pain. The remaining seven had the sensation of touch to various mechanical stimuli. In nine patients, the sensation is located in the weight‐bearing surface of the reconstructed heel. Five patients bear weight on the reconstructed surface at least 6 hours per day. Three participate actively in sports. Split‐thickness skin graft‐muscle flaps were more prone to breakdown than skin flaps. Full‐thickness skin flaps appear necessary for the production of pain sensation and the more discriminating sensations. Preliminary results suggest a functional benefit after sensory reinnervation.

Skin tightening effects of the ultrapulse CO2 laser

This study analyzed the skin tightening or contracture effect of the Ultrapulse carbon dioxide (CO2) laser on the skin of hairless guinea pigs by light and electron microscopic, histologic, and tensiometric evaluations. Two 2 X 2 cm squares of back skin were precision tattooed on each of the animals in the study (n = 12). One square served as the control, and the other square was used as experimental skin. The experimental skin was treated with three passes of the CO2 laser at 500 mJ and 5 W using a 3-mm collimated hand-piece. Skin specimens from three animals were analyzed at 1, 4, 8, and 12 weeks. After three passes, the length of the square was reduced by 27 percent, and the width was reduced by 40 percent. Over the next 12 weeks, as the animals grew, the dimensions of the control areas also increased. The laser-treated areas continued to maintain their contracted dimensions, however. By the 12th week, the laser-treated areas were 28.35 percent shorter in length and 15.5 percent shorter in width than the control areas. Histologic examination demonstrated a significantly higher content of collagen in the reticular layer, which was more compact than that of the normal skin. Electron microscopy revealed that the laser had induced shortening of the collagen fibers (7.45 percent; p = 0.026), which persisted beyond the 12th week. Laser treatment did not significantly alter the tensile strength of the skin, although, at the 8th week, the treated areas had a slightly higher tensile strength.

Laser blepharoplasty with transconjunctival orbicularis muscle/septum tightening and periocular skin resurfacing: a safe and advantageous technique.

Carbon dioxide (CO2) laser blepharoplasty with orbicularis oculi muscle tightening and periorbital skin resurfacing is a safe procedure that produces excellent aesthetic results and diminishes the occurrence of complications associated with skin and muscle resection in the lower lid, particularly permanent scleral show and ectropion. The authors present a review of 196 cases of carbon dioxide laser blepharoplasty and periocular laser skin resurfacing performed at their center from April of 1994 to September of 1998. Of these cases, 113 patients underwent four-lid blepharoplasty, 59 underwent upper lid blepharoplasty only, and 24 underwent lower lid blepharoplasty only. Prophylactic lateral canthopexy was performed in 24 patients. Concomitant procedures (brow lift/rhytidectomy/rhinoplasty) were performed in 92 patients. The carbon dioxide laser blepharoplasty procedure resulted in no injuries to the globe, cornea, or eyelashes. Combined with laser tightening of the orbicularis oculi muscle and septum and periocular skin resurfacing, the transconjunctival approach to lower blepharoplasty preserves lower lid skin and muscle. Elimination of the traditional scalpel skin/muscle flap procedure results in a dramatically lower complication rate, particularly with regard to permanent ectropion and scleral show. Laser shrinkage of the orbicularis muscle and septum through the transconjunctival incision enables the correction of muscle aging changes such as orbicularis hypertrophy and malar festoons. The addition of periocular resurfacing enables the correction of skin aging changes of the eyelid that are not addressed by traditional scalpel blepharoplasty. In addition, lateral canthopexy constitutes an important adjunct to the laser blepharoplasty procedure for the correction of lower lid canthal laxity.