Keith Brandt

Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration

We have fabricated porous, biodegradable tubular conduits for guided tissue regeneration using a combined solvent casting and extrusion technique. The biodegradable polymers used in this study were poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). A polymer/salt composite was first prepared by a solvent casting process. After drying, the composite was extruded to form a tubular construct. The salt particles in the construct were then leached out leaving a conduit with an open-pore structure. PLGA was studied as a model polymer to analyze the effects of salt weight fraction, salt particle size, and processing temperature on porosity and pore size of the extruded conduits. The porosity and pore size were found to increase with increasing salt weight fraction. Increasing the salt particle size increased the pore diameter but did not affect the porosity. High extrusion temperatures decreased the pore diameter without altering the porosity. Greater decrease in molecular weight was observed for conduits manufactured at higher temperatures. The mechanical properties of both PLGA and PLLA conduits were tested after degradation in vitro for up to 8 weeks. The modulus and failure strength of PLLA conduits were approximately 10 times higher than those of PLGA conduits. Failure strain was similar for both conduits. After degradation for 8 weeks, the molecular weights of the PLGA and PLLA conduits decreased to 38% and 43% of the initial values, respectively. However, both conduits maintained their shape and did not collapse. The PLGA also remained amorphous throughout the time course, while the crystallinity of PLLA increased from 5.2% to 11.5%. The potential of seeding the conduits with cells for transplantation or with biodegradable polymer microparticles for drug delivery was also tested with dyed microspheres. These porous tubular structures hold great promise for the regeneration of tissues which require tubular scaffolds such as peripheral nerve, long bone, intestine, or blood vessel.

In vivo evaluation of poly(l-lactic acid) porous conduits for peripheral nerve regeneration

The present study provides in vivo trials of poly(L-lactic acid) (PLLA) as a porous biodegradable nerve conduit using a 10 mm sciatic nerve defect model in rats. The PLLA conduits, fabricated by an extrusion technique, had an inner diameter of 1.6 mm, an outer diameter of 3.2 mm, and a length of 12 mm. They were highly porous with an interconnected pore structure (of 83.5% porosity and 12.1 microm mean pore size). The conduits were interposed into the right sciatic nerve defect of Sprague Dawley rats using microsurgical techniques; nerve isografts served as controls. Walking track analysis was performed after conduit placement monthly through 16 weeks. At the conclusion of 6 and 16 weeks, sections from the isograft/conduit and distal nerve were harvested for histomorphometric analysis. The right gastrocnemius muscle was also harvested and its weight was determined. All conduits remained intact without breakage. Moreover, no conduit elongated during the 16 weeks of placement. Walking track analysis and gastrocnemius muscle weight demonstrated increasing regeneration over the 16 weeks in both the conduit and isograft control groups, with control values significantly greater. The nerve fiber density in the distal sciatic nerve for the PLLA conduits (0.16+/-0.07) was similar to that for the control isografts (0.19+/-0.05) at 16 weeks. The number of axons/mm2 in the distal sciatic nerve for the PLLA conduits was lower than that for the isografts (13 800+/-2500 vs. 10700+/-4700) at 16 weeks. The results for PLLA were significantly improved over those for 75:25 poly(DL-lactic-co-glycolic acid) of a previous study and suggest that PLLA porous conduits may serve as a scaffold for peripheral nerve regeneration.

Nerve Crush Injuries—A Model for Axonotmesis

Nerve crush is a commonly used experimental model in the rat; however, a standard method of inducing this injury has not been defined. This study examined six crush techniques that are frequently used and characterized the subsequent nerve injury. Five types of nerve crush using a No. 5 jewelers forceps and a sixth using a 30-s single crush with a serrated hemostat were studied in the posterior tibial nerve of the Lewis rat. Regeneration was evaluated using serial walking track assessments at 1, 2, 4, 6, and 8 weeks postoperatively. Nerve conduction studies and histological examination were performed at 2 days, 2 weeks, and 8 weeks. Blood-nerve barrier breakdown was observed at 2 days and recovered by 2 weeks. By 4 weeks normal walking track patterns were obtained in all groups. A pattern of Wallerian degeneration and axonal regeneration was noted at 2 weeks, with histological recovery in all groups by 8 weeks. Nerve crush, induced by any of the six methods tested, was similar and provides a reliable model of axonotmesis.

A technique for maximizing biceps recovery in brachial plexus reconstruction

In 21 cadaver dissections the intramuscular anatomy of the musculocutaneous nerve and the relative relationship of the motor and sensory components of this nerve were evaluated. Nearly one half of the fibers entering the musculocutaneous nerve terminate in cutaneous receptors. We report five cases in which biceps reinnervation was performed by a surgical technique that minimizes the period of denervation by using motor nerves (medial pectoral nerves) very close to the biceps muscle. This technique also redirects the cutaneous portion (lateral antebrachial cutaneous nerve) of the musculocutaneous nerve into the biceps muscle to ensure that the motor fibers are not directed toward cutaneous receptors.

Hospital-Associated Costs Due to Surgical Site Infection After Breast Surgery

OBJECTIVE To determine the attributable costs associated with surgical site infection (SSI) following breast surgery. DESIGN AND SETTING Cost analysis of a retrospective cohort in a tertiary care university hospital. PATIENTS All persons who underwent breast surgery other than breast-conserving surgery from July 1, 1999, through June 30, 2002. MAIN OUTCOME MEASURES Surgical site infection and hospital costs. Costs included all those incurred in the original surgical admission and any readmission(s) within 1 year of surgery, inflation adjusted to US dollars in 2004. RESULTS Surgical site infection was identified in 50 women during the original surgical admission or at readmission to the hospital within 1 year of surgery (N = 949). The incidence of SSI was 12.4% following mastectomy with immediate implant reconstruction, 6.2% following mastectomy with immediate reconstruction using a transverse rectus abdominis myocutaneous flap, 4.4% following mastectomy only, and 1.1% following breast reduction surgery. Of the SSI cases, 96.0% were identified at readmission to the hospital. Patients with SSI had crude median costs of

Risk Factors for Surgical Site Infection after Major Breast Operation

16 882 compared with

Clinical long-term in vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration

6123 for uninfected patients. After adjusting for the type of surgical procedure(s), breast cancer stage, and other variables associated with significantly increased costs using feasible generalized least squares, the attributable cost of SSI after breast surgery was

The lateral arm/proximal forearm flap

4091 (95% confidence interval,

Free flaps as flow-through vascular conduits for simultaneous coverage and revascularization of the hand or digit

2839-

A subjective rating scale for evaluating the appearance outcome of autologous breast reconstruction

5533). CONCLUSIONS Surgical site infection after breast cancer surgical procedures was more common than expected for clean surgery and more common than SSI after non-cancer-related breast surgical procedures. Knowledge of the attributable costs of SSI in this patient population can be used to justify infection control interventions to reduce the risk of infection.