Axonal regeneration into Schwann cell grafts within resorbable poly(alpha-hydroxyacid) guidance channels in the adult rat spinal cord.

Axonal growth and myelination in a SC graft contained in a resorbable tubular scaffold made of poly(D,L-lactic acid) (PLA50) or high molecular weight poly(L-lactic acid) mixed with 10% poly(L-lactic acid) oligomers (PLA(100/10)) were studied for up to 4 months after implantation in the completely transected adult rat thoracic spinal cord. The PLA50 tubes collapsed soon after implantation and, consequently, compressed the graft inside, leading to only occasional thin cables with SCs and a low number of myelinated axons: 17 +/- 6 at 1 and 158 +/- 11 at 2 months post-grafting. The cable contained 32 +/- 23 blood vessels at 2 weeks, 55 +/- 33 at 1 month and 46 +/- 30 at 2 months after implantation. PLA(100/10) tubes, on the other hand, were found to break up into large pieces, which compressed and sometimes protruded into the tissue cable inside. At all time points studied, however, cables contained SCs and were well vascularized with 414 +/- 47 blood vessels at 2 weeks, 437 +/- 139 at 1, 609 +/- 134 at 2 and 396 +/- 95 at 4 months post-grafting. The number of myelinated axons was 712 +/- 509 at 1 month, 1819 +/- 837 at 2 months and 609 +/- 132 at 4 months post implantation. These results demonstrated that fiber growth and myelination into a SC graft contained in a resorbable PLA(100/10) tube increases over the first 2 months post-implantation but decreases thereafter. Changes in geometry of both types of polymer tubes were detrimental to axonal regeneration. Future research should explore the use of polymers that better retain the appropriate mechanical, geometrical and permeability properties over time.

Novel synthetic meshwork for glaucoma treatment. I. Design and preliminary in vitro and in vivo evaluation of various expanded poly(tetrafluoroethylene) materials.

A novel drainage implant for glaucoma filtering surgery (MESH) is proposed. After various expanded poly(tetrafluoroethylene) (e-PFTE) materials were evaluated, the feasibility and the short-term safety of the technique were assessed in this first pilot study in the rabbit. The porous structure and the in vitro resistance to aqueous flow of seven different e-PTFE membranes (5-80 microm average pore size) were compared. Eight Dutch pigmented rabbits were implanted with the T-shaped MESH implants made from either 20- or 50-microm average pore size e-PTFE membranes. Clinical examination, intraocular pressure (IOP) measurements, and histology analyses were performed over a period of 3 months. The contralateral nonoperated eyes served as controls. MESH implantation took less than 7 min. No postoperative hypotony, migration, or extrusion of the implant and no intraocular inflammation or infection occurred. A significant IOP reduction in the implanted eyes was obtained past postoperative day 21 with the 20-microm material implant. The drainage efficacy was correlated with the degree of colonization of the porous materials and the inner spacing of the implant as observed by histology. With a filtering patency 3 times longer than conventional trabeculectomy and laser sclerectomy, MESH surgery is a promising technique for glaucoma treatment. Further studies are underway to enhance the device efficacy and understand the mechanism of filtration.

Poly(alpha-hydroxyacids) for application in the spinal cord: resorbability and biocompatibility with adult rat Schwann cells and spinal cord.

Future surgical strategies to restore neurological function in the damaged human spinal cord may involve replacement of nerve tissue with cultured Schwann cells using biodegradable guiding implants. We have studied the in vitro and in vivo degradability of various aliphatic polyesters as well as their effects on rat Schwann cells in vitro and on spinal cord tissue in vivo. In vitro, cylinders made of poly(D,L-lactic-co-glycolic acid) 50:50 (PLA25GA50) started to degrade at 7 days, compared with 28 days for cylinders made of poly(D,L-lactic acid) (PLA50). This faster degradation of PLA25GA50 was reflected by a much higher absorption of water. In vivo, after implantation of PLA25GA50 or PLA50 cylinders between the stumps of a completely transected adult rat spinal cord, the decrease in molecular weight of both polymers was similar to that found in vitro. In vitro degradation of poly(L-lactic acid) (PLA100) mixed with increasing amounts of PLA100 oligomers also was determined. The degradation rate of PLA100 mixed with 30% oligomers was found to be similar to that of PLA50. In vitro, PLA25GA50 and the breakdown products had no adverse effect on the morphology, survival, and proliferation of cultured rat Schwann cells. In vivo, PLA25GA50 cylinders were integrated into the spinal tissue 2 weeks after implantation, unlike PLA50 cylinders. At all time points after surgery, the glial and inflammatory response near the lesion site was largely similar in both experimental and control animals. At time points later than 1 week, neurofilament-positive fibers were found within PLA25GA50 cylinders or the remains thereof. Growth-associated protein 43, which is indicative of regenerating axons, was observed in fibers in the vicinity of the injury site and in the remains of PLA25GA50 cylinders. The results suggest that poly(alpha-hydroxyacids) are likely candidates for application in spinal cord regeneration paradigms involving Schwann cells.