Surface modified surgical instruments, medical devices, implants, contact lenses and the like

Improved medical devices and instruments prepared by an improved method of producing hydrophilic, gamma-irradiation induced polymerized and chemically grafted coatings on plastic surfaces of articles adapted for contacting living tissue, the improvement comprising carrying out the graft polymerization in an aqueous solution under specific combinations of the following conditions: PA1 (a) monomer concentration in the range of from about 0.1% to about 50%, by weight; PA1 (b) total gamma dose in the range of from about 0.001 to less than about 0.50 Mrad; and PA1 (c) gamma dose rate in the range of from above about 2,500 to about 10.sup.8 rads/minute.

RELATED APPLICATIONS 
The invention described in this application is related to those described 
in U.S. Pat. Nos. 5,094,876, 5,100,689 and 5,290,548 which are 
continuations-in-part of application Ser. No. 07/304,479 filed Feb. 1, 
1989 (now U.S. Pat. No. 4,961,954) which is a continuation-in-part of 
application Ser. No. 07/037,153 filed Apr. 10, 1987 (now U.S. Pat. No. 
4,806,382). The entire disclosures of each of the above-listed patents are 
incorporated herein by reference. 
BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to plastic surgical instruments, medical 
devices, prosthetic cardiovascular implants and implants for hard and soft 
tissue, contact lenses and the like and methods for improving surfaces 
thereof. 
2. Discussion of the Prior Art 
Studies have shown that the surgical implantation of ocular implants such 
as intraocular lenses (IOL) and the like can result in the loss of 
significant corneal endothelial tissue unless great care is taken to 
ensure a lack of contact between the device and the endothelium. Most 
ocular implants are constructed of hydrophobic polymethylmethacrylate 
(PMMA) polymers because of their superior optical qualities, resistance to 
biodegradation and the like. It has been found, however, that PMMA 
surfaces adhere to endothelial cells upon even casual contact and that 
separation of the surface therefrom results in a tearing away of the 
endothelial tissue adhered to the polymer surface. Similar adhesive 
interactions with other ocular tissues, i.e., the iris, can also cause 
adverse tissue damage. Other hydrophobic polymers which are used or have 
been proposed for use in ocular implants (i.e., polypropylene, 
polyvinylidene fluoride, polycarbonate, polysiloxane) also can adhere to 
ocular tissue and thereby promote tissue damage. 
It is well documented in the prior art that a significant disadvantage 
inherent in PMMA IOLs resides in the fact that any brief, non-traumatic 
contact between corneal endothelium and PMMA surfaces results in extensive 
damage to the endothelium. See Bourne et al, Am. J. Ophthalmol., Vol. 81, 
pp. 482-485 (1976); Forster et al, Trans. Am. Acad. Ophthalmol. 
Otolaryngol., Vol. 83, OP-195-OP-203 (1977); Katz et al, Trans. Am. Acad. 
Ophthalmol. Otolaryngol., Vol. 83, OP-204-OP-212 (1977); Kaufman et al, 
Science, Vol. 198, pp. 525-527 (1977) and Sugar et al, Arch. Ophthalmol., 
Vol. 96, pp. 449-450 (1978) for a discussion of the problem associated 
with implant surface/endothelium contact. 
Since it is extremely difficult to avoid any contact between implant 
surfaces and endothelium during surgical procedures and especially to 
other sensitive ocular tissues during implant life, i.e., the iris, 
ciliary sulcus and the like, efforts have been undertaken to modify the 
PMMA ocular implant surfaces to reduce the tendency thereof to adhere to 
and damage corneal endothelium. 
Ocular implant surfaces have been coated with various hydrophilic polymer 
solutions or temporary soluble coatings such as methylcellulose, 
polyvinylpyrrolidone Katz et al, supra, and Knight et al, Chem. Abs., 
Vol. 92:203547f (1980)! to reduce the degree of adhesion between the 
implant surfaces and tissue cells. While offering some temporary 
protection, these methods have not proven entirely satisfactory since such 
coatings complicate surgery, do not adhere adequately to the implant 
surfaces, become dislodged or deteriorate after implantation, dissolve 
away rapidly during or soon after surgery or may produce adverse 
post-operative complications. Moreover, it is difficult to control the 
thickness and uniformity of such coatings. 
Yalon et al Acta: XXIV, International Congress of Ophthalmology, ed. Paul 
Henkind (1983)! and Knight et al, supra, have reported attempts to produce 
protective coatings on PMMA implant surfaces by gamma-radiation induced 
polymerization of vinylpyrrolidone thereon. Their efforts were not 
altogether successful, however, since their methods also presented 
problems in controlling the optical and tissue protective qualities of the 
coatings. Process conditions and parameters (i.e., monomer concentration 
solvent, dose and dose rate) were not specified. The resulting coatings 
were of poor quality and non-uniform mechanical stability. 
Gamma-PVP treatment of PTFE has been reported, but under severe process 
conditions requiring gamma doses above 1 Mrad which are impractical in 
that both bulk and surface properties of the PTFE are changed Boffa et 
al, J. Biomed. Mater. Res., Vol. 11, p. 317 (1977)!. Non-aqueous solutions 
of high monomer concentrations (50% NVP in pyridine) are required at 
relatively high doses of gamma radiation (1-5 Mrad), resulting in a high 
degree of grafting, but with extensive changes in the bulk and surface 
properties of the PTFE since PTFE is readily degraded at gamma doses above 
1 Mrad. 
In U.S. Pat. No. 4,806,382 issued Feb. 21, 1989, there are described 
improved methods for producing hydrophilic, gamma-irradiation induced 
polymerized and chemically grafted coatings on ocular implants constructed 
of a variety of polymeric materials, which methods overcome the 
above-noted difficulties and disadvantages. 
The invention described in that application is predicated on the discovery 
of certain process conditions and parameters that produce thin hydrophilic 
gamma-irradiation induced polymerized and chemically grafted coatings of 
N-vinyl-pyrrolidone (NVP) PVP!, copolymerized NVP and 
2-hydroxyethylmethacrylate (HEMA) P(NVP-HEMA)!, or HEMA PHEMA! and their 
copolymers, particularly with ionic comonomers on the surfaces of ocular 
implants constructed of materials including polymethylmethacrylate (PMMA) 
and of other process conditions and parameters which produce thin 
gamma-irradiation induced graft PVP, P(NVP-HEMA), PHEMA or copolymer 
coatings on the surfaces of ocular implant articles constructed of 
materials including polypropylene (PP), polyvinylidene fluoride (PVDF), 
polycarbonate (PC) and polysiloxane (PDMSO) or silicone (PSi). The 
coatings increase the hydrophilicity of the implant surface and minimize 
adhesion between the surface and sensitive ocular tissues such as corneal 
endothelium or iris thereby minimizing tissue damage and post-operative 
complications occasioned by contact between the implant surface and ocular 
tissue. The coatings produced by the improved method of the invention 
described in U.S. Pat. No. 4,806,382 are thin and reproducibly uniform. 
Moreover, they are chemically bound to the surface of the ocular implant 
and, therefore, far more durable and less subject to removal, degradation 
or deterioration during or following surgery than the coatings produced by 
prior art methods. 
The improved gamma-irradiation induced graft polymerization of NVP, HEMA or 
mixtures of NVP and HEMA on ocular implant surfaces comprising PMMA to 
form optimum PVP, P(NVP-HEMA) or PHEMA graft polymer surface modifications 
thereon described in U.S. Pat. No. 4,806,382 comprises carrying out the 
graft polymerization in an aqueous solution under specific combinations of 
the following conditions: 
(a) monomer concentration in the range of from about 0.5 to about 50%, by 
weight; 
(b) total gamma dose in the range of from about 0.01 to about 0.50 Mrad; 
(c) gamma dose rate in the range of from about 10 to about 2,500 
rads/minute; and 
(d) maintaining the molecular weight of the polymer in solution in the 
range of from about 250,000 to about 5,000,000. 
The maintenance of the molecular weight of the polymer in solution at 
certain values, identified in U.S. Pat. No. 4,806,382 as a critical 
condition of the method, is not actually a "condition" of the method, but 
rather, as stated in the specification, a result which is dependent on the 
reaction conditions employed in carrying out the graft polymerization 
process. It is, therefore, not appropriate to specify the molecular weight 
of the polymer in solution as a process "condition" since it is rather an 
outcome of the reaction conditions used in this invention and may be 
widely varied depending on specific gamma graft monomer-substrate-process 
conditions. If a certain set of fixed conditions are employed (namely, 
monomer, monomer concentration, total gamma dose, gamma dose rate and 
radical polymerization inhibitors), the molecular weight of the polymer 
formed in solution will be an output of the process which is dependent 
upon the values of the above-noted monomer, monomer concentration, total 
gamma dose, gamma dose rate and radical polymerization inhibitor 
conditions. For example, in the presence of certain ionic monomers, 
solvents or radical inhibitors, solution polymerization may be 
significantly inhibited without sacrificing efficient surface graft 
polymerization and the resulting solution polymer molecular weight may 
thereby be relatively low (i.e., as low as 5,000-10,000). 
Since the application which matured into U.S. Pat. No. 4,806,382 was filed, 
the inventors of the subject matter defined therein conducted additional 
research and unexpectedly found that although relatively low doses of 0.01 
to 0.20 Mrad are generally preferred for the compositions of this 
invention, the process could be conducted at a total gamma dose as low as 
0.001 Mrad. 
The state of the art prior to the application which matured into U.S. Pat. 
No. 4,806,382 taught the use of relatively high gamma doses, generally 
greater than 0.5 Mrad, for gamma polymerization grafting and it was, 
therefore, surprising to find that surface grafting could be achieved at 
doses as low as 0.01 Mrad. The achievement of effective grafting at doses 
as low as 0.001 Mrad is, consequently, an even more unexpected result of 
the process of this invention. Furthermore, although grafting with monomer 
concentrations as low as 0.5 wt. % was indicated in prior U.S. Pat. No. 
4,806,382, further research has revealed that monomer concentrations as 
low as 0.1 wt. % may be utilized in some embodiments of the graft process 
of this invention. 
Optimally, the method may also be carried out under one or more of the 
following conditions: 
(e) substantially excluding free oxygen from the aqueous graft 
polymerization solution; 
(f) maintaining the thickness of the PVP or P(NVP-HEMA) surface graft in 
the range of from about 100 .ANG. to about 150 microns; 
(g) including a free radical scavenger in the aqueous graft polymerization 
solution; and 
(h) including in the aqueous graft polymerization solution a swelling 
solvent for PMMA or other polymer substrate surface. 
The improved gamma-irradiation induced graft polymerization of NVP, 
mixtures of NVP and HEMA or HEMA and other hydrophilic monomers or their 
copolymers on ocular implant surfaces comprising PP, PVDF, PC or PDMSO to 
form optimum PVP or P(NVP-HEMA) graft polymer surface grafts thereon may 
also be carried out under specific combinations of the process parameters 
as indicated above for PMMA, but also under conditions which involve 
excluding free oxygen from the polymerization solution for preferred 
surface modification of these ocular implant polymer substrates. 
At the present time, surgical instruments, medical devices, prosthetic 
implants, contact lenses and the like which are intended for contact with 
blood or with sensitive tissue surfaces are constructed of materials 
having the necessary physical properties to enable their use for the 
intended application; however, they suffer from the disadvantage that due 
to the generally hydrophobic nature of the blood or tissue contacting 
surfaces thereof, they exhibit undesired thrombogenic properties and 
significant damage may occur to fragile or sensitive tissues by adhesion 
and manipulation or movement on contact with these instruments. 
In U.S. Pat. No. 4,961,954, there are described improved methods for 
producing hydrophilic, gamma-irradiation induced polymerized and 
chemically grafted coatings on such instruments, devices and the like so 
constructed of a variety of polymeric materials. 
The invention described in the above-noted patent is predicated on the 
discovery of certain process conditions and parameters that produce thin, 
hydrophilic, gamma-irradiation polymerized and chemically grafted coatings 
of N-vinylpyr-rolidone (NVP PVP!), copolymerized NVP and 
2-hydroxyethyl-methacrylate (HEMA) P(NVP-HEMA)! or HEMA PHEMA! on the 
surfaces of articles adapted for contact with living tissue of a human or 
non-human animal, e.g., surgical instruments, medical devices, prosthetic 
implants, contact lenses and the like constructed of a wide variety of 
plastic materials. For purposes of the following description of the 
invention, the term "tissue" is intended to include blood as well as solid 
tissue surfaces. 
The surface modifications or chemically grafted coatings of the invention 
increase the hydrophilicity of the article surfaces and minimize adhesion 
between the surface and sensitive tissues such as blood cells, vascular 
endothelium, peritoneum, pericardium and the like, thereby minimizing 
tissue damage and complications occasioned by contact between the article 
and such tissues. The coatings produced are thin and reproducibly uniform. 
Moreover, they are chemically bound to the surface of the article and, 
therefore, are far more durable and less subject to removal, degradation 
or deterioration during or following utilization of the articles than the 
coatings produced by prior art methods. 
The improved gamma-irradiation induced graft polymerization of NVP, HEMA or 
mixtures of NVP and HEMA on plastic article surfaces to form optimum PVP, 
P(NVP-HEMA) or PHEMA graft polymer surface modifications thereon described 
in U.S. Pat. No. 4,961,954 comprises carrying out the graft polymerization 
in an aqueous solution under specific combinations of the following 
conditions: 
(a) monomer concentration in the range of from about 0.5 to about 50%, by 
weight; 
(b) total gamma dose in the range of from about 0.01 to about 0.50 Mrad; 
(c) gamma dose rate in the range of from about 10 to about 2,500 
rads/minute; and 
(d) maintaining the molecular weight of the polymer in solution in the 
range of from about 250,000 to about 5,000,000. 
Optimally, the method may also be carried out under one or more of the 
following conditions: 
(e) substantially excluding free oxygen from the aqueous graft 
polymerization solution; 
(f) maintaining the thickness of the PVP or P(NVP-HEMA) surface graft in 
the range of from about 100 .ANG. to about 100 microns; 
(g) including a free radical scavenger in the aqueous graft polymerization 
solution; and 
(h) including in the aqueous graft polymerization solution a swelling 
solvent for PMMA or other polymer substrate surface. 
The invention described in U.S. Pat. No. 5,100,689 relates to plastic 
articles and methods for their manufacture wherein lower dosages are 
employed and the manufacture of molecular weight is not a "condition" of 
the process. 
The invention described in U.S. Pat. No. 5,094,876 relates to plastic 
articles and methods for their manufacture wherein the article surface is 
first pre-soaked in a solution comprising the monomer prior to graft 
polymerizing the monomer onto the surface. 
It is an object of the present invention to provide a still further 
improved method for producing hydrophilic coatings on the surfaces of such 
articles, as well as the articles produced by the improved method. 
SUMMARY OF THE INVENTION 
It has been discovered that gamma dose rates much greater than those 
specified in the above-discussed patents may be employed in carrying out 
the methods described therein for producing the plastic articles. 
More particularly, it has been found that gamma dose rates up to about 
10.sup.8 rads/minute may be employed which enables a significant reduction 
in the time required to produce the improved plastic articles. 
The invention also includes articles produced according to the 
above-described method. 
DETAILED DESCRIPTION OF THE INVENTION 
Yalon et al (supra) and Knight et al (supra) disclose gamma-irradiation 
coatings on PMMA using N-vinylpyrrolidone (NVP) and 
2-hydroxyethylmethacrylate (HEMA) and indicate poor dynamic (abrasive) 
protection of endothelium for these coatings. Dissolvable coatings of 
polyvinyl-alcohol (PVA) were regarded as optimal for intraocular lenses 
(IOLs) by Knight et al, supra, and commercial development of a PVA-coated 
IOL was attempted with unsatisfactory clinical results. The gamma 
polymerization surface modifications reported were carried out under 
process conditions of monomer concentration, solvent, dose and dose rate 
which were not specified and which apparently yielded poor quality, 
readily abraded coatings. Conditions for producing useful permanent PVP or 
PHEMA coatings on PMMA IOLs or any other plastic surface are not taught in 
the prior art. Neither Knight et al, Yalon et al or the literature on 
gamma-graft polymerization of the past 30 years suggests the process 
conditions required to achieve the complicated requirements for useful 
ocular implant coatings. These requirements include: 
(a) Thin, permanent, optically clear (in the case of contact lenses) and 
uniform graft coatings. The literature generally discloses conditions 
which produce distortion and degradation of the substrate due to the use 
of high gamma-irradiation doses (&gt;1 Mrad) and non-aqueous solvent media, 
and yield thick, cloudy, non-uniform coatings e.g., Chapiro, Radiation 
Chemistry of Polymeric Systems, John Wiley and Sons, Inc., New York 
(1962); Henglein et al, Angew. Chem., Vol. 15, p. 461 (1958)!. 
(b) Long-term biocompatibility in vivo. 
(c) Low contact angle (high wettability) for water or underwater air bubble 
(less than about 30.degree.). 
(d) Non-adherent to tissue (adhesive force to endothelium less than about 
150 mg/cm.sup.2). 
(e) Non-damaging to endothelium (less than ca. 20% damage for in vitro 
contact tests). 
(f) Graft coating may be measurable by ESCA or FTIR analysis. 
(g) Abrasion resistance by sliding (dynamic) friction testing showing no 
change in wetting (contact angle) and confirming before and after presence 
of graft coating. 
(h) Rapid hydration--change from dry state to wetted lubricous state on 
immersion in water (within five minutes). 
Yalon et al (supra) disclose an in vitro technique for measuring 
endothelium damage. Results for PMMA were used to illustrate the method. 
Although it was noted that PVP coatings reduced cell damage with less 
damage at higher monomer concentrations, the conditions for the experiment 
(i.e., irradiation dose, dose rate and the like) were not disclosed, nor 
were any of the critical process-product relationships indicated. 
The improved process conditions and parameters of the invention described 
in U.S. Pat. No. 4,961,954 which are necessary to produce useful polymers 
having a surface modified by gamma-irradiation induced graft 
polymerization therein of PVP, P(NVP-HEMA) or PHEMA include: % monomer, 
gamma dose, dose rate and oxygen (air) degassing. Other optimal process 
conditions include catalysts, free radical scavengers, PMMA swelling 
solvents and temperature. The solution polymer molecular weight and M.W. 
distribution, the % conversion and residual monomer, the graft polymer 
thickness and surface properties and the like are process results which 
can change markedly as the process variables change. For example, the 
surface modification achieved for PVP on polymer surfaces will be 
different when using 10% monomer and 0.1 Mrad if prepared at low dose 
rates since low dose rates (slower polymerization) favor higher molecular 
weights. Similarly, degassed oxygen-free reaction media result in improved 
grafts at much lower doses. The presence of free radical scavengers such 
as copper or iron salts or organic reducing agents (i.e., ascorbic acid) 
also greatly influences other process parameters, generally reducing 
solution polymer molecular weight and preventing solution gelation at high 
monomer concentrations. 
The method of the invention is applicable for the surface modification of 
medical instruments, devices, implants and contact lenses formed from a 
variety of plastic materials including, for example, poly-acrylates and 
-methacrylates (i.e., polymethylmethacrylate, polyethyl acrylate, 
polybutyl methacrylate, etc.); polyolefins (polyethylene, polypropylene, 
polybutadiene); SBS (styrene-butadiene); ethylene-propylene copolymers; 
SE/BS (styrene-ethylene/butadiene); polycarbonates (PC); fluorocarbon 
polymers i.e., polyvinylidene fluoride (PVDF), poly-tetrafluoroethylene 
(PTFE), polyperfluoroethylenepropylene (FEP), polysiloxanes!; various 
aliphatic and aromatic polyurethanes, including polyurethane polyester or 
polyether block copolymers, polyvinylchloride and various polyesters, 
including dacron PET. 
Any medical instrument, device, implant and the like constructed of one or 
more of the above materials may be surface modified according to the 
present invention to improve the tissue contacting characteristics of the 
surfaces thereof. 
Plastic surgical instruments and implements such as probes, retractors, 
tissue and vessel separators, irrigation and aspiration tools, 
phacoemulsification tools, sponges, clamps, gloves, lens glides, 
positioning tools, forceps, insertion tools, staples, sutures and the like 
may be treated in accordance with the present invention. 
Medical devices such as hard and soft contact lenses, intravenous and 
central venous catheters, laser and balloon angioplasty devices, vascular 
and heart devices (tubes, catheters, balloons), ventricular assists, blood 
dialysis components, blood oxygenators, ureteral/urinary devices (Foley 
catheters, stents, tubes and balloons), airway catheters (endotracheal and 
tracheostomy tubes and cuffs), enteral feeding tubes, wound drainage 
tubes, blood bags and blood tubing may also be beneficially treated in 
accordance with the method o the present invention. 
Implants which may be modified according to the present invention include, 
for example, vascular grafts, soft and hard tissue prostheses (mammary, 
cranio/facial, tendons, joints), heart valves and artificial hearts. 
Modification of these medical instruments, devices, implants and the like 
improves the surfaces thereof so as to improve blood compatibility and 
reduce tissue adhesion and tissue damage during surgical contact and 
manipulation. Moreover, the invention operates to reduce cell adhesion for 
reduced inflammation, reduce fibrous capsule formation for soft tissue 
implants, and reduce thrombogenicity for cardiovascular devices and 
prostheses. The invention also acts to reduce bacterial adhesion and 
thereby reduce the incidence of infection and further operates to reduce 
interfacial abrasion and friction which is of special value for joint and 
tendon prostheses. 
Polyolefins and polyolefin/hydrocarbon block polymers are useful for 
constructing medical tubing, catheters, blood bags, sutures and the like. 
Copolymers of the SBS, EP or SE/BS type may be thermoplastic elastomers 
which combine rubbery properties with extrudable or injection moldable 
processing properties. Surface modification of such materials according to 
the present invention is effective in changing the normal surface 
characteristics of these polymers from hydrophobic to hydrophilic. 
The fluorocarbon polymers are widely used for catheters (i.e., intravenous 
catheters), for vascular prostheses (i.e., vascular grafts) and for 
coating medical devices, instruments and implants due to their 
biocompatibility and inertness. However, the surface properties may be 
improved significantly according to the present invention to reduce cell 
and tissue adhesion and improve blood compatibility. 
The silicone polymers are widely used for medical tubing and catheters, for 
mammary implants and other soft tissue prostheses. Hydrophilic surface 
modification, according to this invention, acts to reduce cell and tissue 
abrasion and adhesion and to thereby reduce fibrous capsule formation 
which is a major complication of soft tissue implants. Similarly, 
polyvinylchloride surface modification to produce more hydrophilic vinyl 
tubing and film surfaces can reduce thrombogenicity and improve 
biocompatibility of blood tubing, blood bags, catheters and other medical 
devices made of polyvinylchloride. 
Polyurethanes which are used for such applications as pacer leads, 
intravenous catheters, enteral feeding tubes, vascular grafts and the like 
are also beneficially modified by the process and materials of this 
invention to produce more hydrophilic surfaces and make such devices more 
biocompatible. 
Each of the above-described process conditions and parameters of the method 
of the invention may be varied within the ranges discussed below to 
produce certain specific combinations which are particularly advantageous 
for the surface modification of a particular polymeric surface. 
(a) Monomer concentration: Increasing monomer concentration increases 
polymer molecular weight in the graft solution and reduces contact angle 
(C.A.), i.e., renders the surface more hydrophilic. For example, in the 
case of forming PVP coatings on PMMA, in the range of from about 3-15% 
NVP, the PVP viscosity molecular weight (M.sub.v) increases from 560,000 
to 2,700,000 and the PMMA graft C.A. decreases from 29.degree. to 
21.degree. at 0.1 Mrad and 309 rads/minute. However, this effect is 
sensitive to dose rate and total dose. For example, at 1-10% NVP, but at a 
lower dose rate of 64 rads/minute, the molecular weight increases from 
400,000 to 4,590,000 and the C.A. decreases from 49.degree. to 18.degree.. 
In general, monomer concentrations in the range of 0.1-50% are preferred 
depending on other parameters. Concentrations as low as 0.1 to 0.5% at low 
dose rates can yield hydrophilic surface grafts with C.A. below 
30.degree.-40.degree. under conditions of this invention. At monomer 
concentrations greater than 20-30%, effective grafting without solution 
polymer gelation requires low doses and use of free radical scavengers. 
Monomer concentrations greater than 50% are feasible, but not preferred, 
since high concentrations of radical scavengers must be used and polymer 
molecular weights and monomer conversion are lowered significantly by 
their use. For producing PHEMA coatings, HEMA concentrations of between 
0.5% and 10%, by weight, are sufficient. 
(b) Dose: In general, increasing total gamma dose increases molecular 
weight of the polymer and reduces the contact angle. However, an important 
practical limit exists in that at higher doses, lower dose rates and 
higher monomer concentrations, reaction media become extremely viscous or 
form gels which are very difficult to wash and to remove (e.g., about 0.25 
Mrad and 10% NVP at 309 rads/minute). 
(c) Dose rate: Decreasing the gamma radiation dose rate, generally 
increases solution polymer M.W., e.g., from 1,150,000 to 5,090,000 at 10% 
NVP and 0.1 Mrad as dose rate decreases from 1,235 to 49 rads/minute. The 
C.A. also goes down at lower dose rates, i.e., from 31.degree. to 
15.degree.. It is a feature of the present invention that the gamma dose 
rate may be increased to 10.sup.8 rads/minute which considerably shortens 
the time required to carry out the process. 
(d) Solution Polymer Molecular Weight: The molecular weight may vary widely 
depending upon process conditions, monomers and radical inhibitors used. 
Effective grafting with low C.A. may, therefore, be achieved with even low 
molecular weight solution polymer (M.sub.v as low as 5,000-10,000). 
However, solution polymer M.sub.v greater than 5,000,000 or gels which 
form during grafting are generally less practical because of washing 
problems. 
(e) Degassing: Removal of oxygen from the graft solutions by a vacuum 
and/or an inert gas (e.g., argon purging) can have an important effect: 
lower total doses are required (practical grafting at less than 0.1 Mrad). 
Oxygen degassing also has a significant effect on PVP M.sub.w and % 
conversion of monomer. For example, with degassing, good grafting of PVP 
on polypropylene (PP) is achieved at 0.05 Mrad and 10% NVP (C.A. 
15.degree.). Without degassing, little grafting occurs under these 
conditions. Oxygen degassing is critical to hydrophilic surface 
modification grafting where the substrate polymer is PP, PVDF or PDMSO. It 
has been found that graft polymerization is inefficient when using these 
materials as substrates in the presence of oxygen. Oxygen degassing is 
also beneficial for PMMA and PC substrates in that much lower radiation 
doses (0.01-0.15 Mrad) become effective compared with grafting these 
polymers in the presence of oxygen. 
(f) Graft thickness: Surface grafts less than 100-200 .ANG., although 
non-adhesive and hydrophilic, are useful, but may exhibit somewhat less 
mechanical "softness" or compliant gel-like surfaces than thicker coatings 
for reduced tissue-contact trauma. Graft coatings greater than ca. 300-500 
.ANG. (or 0.03-0.05 microns) up to 50 microns or more are probably more 
desirable for many applications as long as they are smooth, uniform, 
optically clear for optic surfaces, and quickly hydrated. 
Using no swelling solvents and no prolonged monomer contact with substrates 
prior to irradiation, surface grafts which exhibit desired properties 
under preferred process conditions have thicknesses of about 0.1 to 5 
microns. However, using swelling solvents such as ethyl acetate, polymer 
grafts on PMMA of 100 microns or more can be prepared. For certain 
applications, it may be preferred to have thicker "spongy" coatings of 
20-100 microns. 
(g) Free-Radical Scavengers: Free-radical traps, usually reducing agents 
such as Cu.sup.+, Fe.sup.+2, ascorbic acid and the like are known to 
inhibit radical polymerization in solution and thus be effective 
(especially at high gamma doses, high dose rates and high monomer 
concentrations) in slowing the onset of solution gelation during grafting. 
However, under practical grafting conditions, this may result in lower 
molecular weights, high concentrations of unreacted monomer and broad 
molecular weight distributions. Use of metal salts may also be 
objectionable where maximum biocompatibility is critical. 
Although most preferred graft conditions avoid the use of radical 
scavengers, useful conditions for graft coatings of PVP, P(NVP-HEMA) or 
PHEMA have also been defined using ascorbic acid to limit high viscosity 
and gelation of the graft polymer solution. These conditions use high 
monomer concentrations (up to 50%) and thicker grafts are obtained using 
ethyl acetate as a swelling solvent (0.5-5%). 
(h) Swelling solvents: The use of substrate polymer solvents in the aqueous 
monomer grafting solution facilitates swelling and monomer diffusion into 
the polymer before and during gamma polymerization. Penetration of 
monomers into the substrate increases graft coating thickness and enhances 
bonding to the surface. Solvents such as ethyl acetate have been shown to 
greatly facilitate this process with some substrates such as PMMA. 
Although the above-described method represents a significant improvement 
over prior art methods, optimum results in each case depend upon the 
selection of a combination of numerous process parameters and conditions. 
The foregoing method is greatly simplified and the surface grafts are 
significantly enhanced by the method of the present invention according to 
which the substrate to be surface-modified is pre-soaked in a grafting 
monomer (or mixture of monomers) or in a first aqueous solution having a 
concentration of from about 5% to about 95%, by weight, of the grafting 
monomer (or mixture of monomers) for a period of time and at a temperature 
sufficient to facilitate diffusion of the monomers(s) into the substrate 
surface. This pre-soaking step avoids the necessity for utilizing organic 
swelling solvents. These swelling solvents unduly complicate the final 
coating procedure since they must be completely washed away and may 
promote crazing or cracking of the substrate polymers. 
The monomer pre-soaking method of the present invention results in a 
controlled diffusion of monomer into the substrate and may often produce 
what may be regarded as an interpenetrating subsurface polymer structure 
for the ultimately formed hydrophilic polymer graft surface modification. 
The latter is rendered more durable by the thus formed anchoring 
substructure. This monomer pre-soak improvement is also beneficially 
conducted with mixed monomers wherein one hydrophilic monomer is used as 
the pre-soak monomer and a second hydrophilic monomer is used for the 
subsequent gamma polymerization grafting step. This is particularly 
advantageous, for example, with polysiloxane surface modification wherein 
a first monomer pre-soak of a monomer such as 
dimethylaminoethylmethacrylate followed by aqueous NVP present as the 
medium during gamma irradiation, results in a more stable, reproducible, 
hydrophilic surface for the highly flexible polysiloxane structure. 
For PMMA substrates, the pre-soaking is preferably conducted at a 
temperature of from about 25.degree. C. to about 80.degree. C. for from 
about 0.5 to about 24 hours or more (up to about 48 hours) using a first 
aqueous solution containing from about 5% to about 50%, by weight, of 
monomer(s) to achieve optimum diffusion thereof into the PMMA substrate. 
Where the substrate surface is polypropylene (PP), polyvinylidene fluoride 
(PVDF), a polycarbonate (PC), a polysulfone (PSF) or a polysiloxane 
(PDMSO), the surface is preferably pre-soaked in the monomer(s) or a first 
aqueous solution containing from about 5% to about 95%, by weight, of 
monomer(s), at a temperature of from about 25.degree. to about 90.degree. 
C., and for from about 0.5 to about 24 hours or more (up to about 48 
hours), to achieve maximum and optimum diffusion of the monomer(s) into 
the substrate surface. 
Where mixtures of NVP and HEMA are employed to form graft copolymerized 
coatings of P(NVP-HEMA), the mixtures may contain up to about 50% by 
weight of HEMA based on the weight of the monomer mixture. However, above 
20-30% HEMA, radical scavengers and low monomer concentrations should be 
used to prevent gelation since HEMA enhances the onset of gelation. 
It will be understood by those skilled in the art that the PVP, P(NVP-HEMA) 
or PHEMA graft coatings of this invention may be modified by 
copolymerization with various ionic monomers including use of such 
monomers for the pre-soak step. Mixtures of non-ionic hydrophilic monomers 
and ionic monomers may also be copolymerized therewith. For example, graft 
copolymerization incorporating vinylsulfonic acid, styrene sulfonic acid, 
sulfoethylmethacrylate, sulfopropylmethacrylate or other vinyl sulfonic 
acids or vinylcarboxylic acids such as acrylic acid, crotonic acid or 
methacrylic acid can afford surface modifications which are anionic. 
Similarly, graft copolymerization incorporating basic or amino-functional 
monomers, e.g., vinylpyridines, aminostyrenes, aminoacrylates or 
aminomethacrylates such as dimethylaminoethylmethacrylate or 
dimethylaminostyrenes afford surface modifications which are cationic. It 
is also useful to use salts of ionic monomers or to convert ionic grafts 
to the salt form by post-treatment. 
Amounts of ionic monomers up to about 50 wt. % of the total monomer weight 
may be employed, it being understood that the critical process parameters 
listed above may be maintained. 
In general, choice of the "best" process will depend upon molecular 
structure of the substrate and grafting polymer and the coating thickness 
desired. In general, those conditions which produce extreme solution 
viscosities and gels or conditions which could produce solvent stress 
cracking or crazing of the IOL polymers should be avoided. By way of 
example, the following process conditions are representative of practical 
conditions for the preparation of improved PVP grafts on various polymer 
substrates according to this invention. 
(a) For PVP grafts on PP, PVDF and PDMSO, or combinations thereof, pre-soak 
the substrate in NVP monomer at 60.degree. C. for 4 hours followed by 
graft polymerization in 10% aqueous NVP with about 0.15 Mrad gamma 
radiation at about 500 rads/minute dose rate, but also as high as 10.sup.8 
rads/minute dose rate. 
(b) For PVP grafts on PMMA, PP, PVDF and PDMSO, or combinations thereof, 
pre-soak the substrate in 40% aqueous NVP monomer at about 60.degree. C. 
for 4 hours followed by graft polymerization in 10% aqueous NVP with about 
0.15 Mrad gamma radiation at about 500 rads/minute dose rate, but also as 
high as 10.sup.8 rads/minute dose rate. 
c) For PVP grafts on PMMA, PDMSO and PC, or combinations thereof, pre-soak 
the substrate in 40% aqueous NVP monomer at about 60.degree. C. for 12 
hours followed by graft polymerization in 10% aqueous NVP with about 0.15 
Mrad gamma radiation at about 500 rads/minute dose rate, but also as high 
as 10.sup.8 rads/minute dose rate. 
All percentages expressed in the following non-limiting example are by 
weight unless otherwise stated. 
All contact angles (C.A.) and other surface characterizations for gamma 
polymerization grafts, unless otherwise indicated, are for samples washed 
with water or water-alcohol at room temperature or elevated temperatures 
to remove soluble residual monomer and ungrafted polymer for the improved 
surface graft processes of this invention. The resulting graft polymers 
are stable and permanent for long-term implants and are not dissolved by 
aqueous media. 
It will also be understood by those skilled in the art that the medical 
instruments, devices and the like to be graft coated may be also 
constructed of materials other than PMMA, PP, PVDF, PC or PDMSO to 
facilitate their use. It will be understood by those skilled in the art 
that such materials may also be at least partially graft polymer surface 
modified so as to improve their properties. 
The methods of the invention may be carried out identically to those 
described in U.S. Pat. Nos. 4,806,382; 4,961,954; 5,108,776; 5,130,160 and 
5,290,548, with the exception that dose rates up to 10.sup.8 rads/minute 
are employed.

The invention is illustrated by the following non-limiting example. 
EXAMPLE 
PMMA slab samples were washed twice each by soap solution and distilled 
water using a sonicator. After complete drying, the samples were put into 
NVP solutions in glass vials. The samples were then .gamma.-irradiated at 
various conditions. After .gamma.-irradiation, the surface modified PMMA 
samples were rinsed several times with H.sub.2 O and evaluated. 
The polymerized NVP grafting solutions or gels were freeze-dried under a 
vacuum. 
PVP grafted PMMA samples were evaluated by water drop or underwater air 
bubble contact angle measurements. The bubble technique is regarded as 
more reliable for very hydrophilic surfaces. For air bubble contact angle, 
the grafted PMMA was held horizontally in distilled water. An 
approximately 0.8 .mu.l air bubble was formed and positioned underneath 
the test surface. Angles on opposite sides of the bubble were measured 
assuring symmetry. Five measurements were usually made for each sample. 
The results are set forth in the following table. 
TABLE 
______________________________________ 
Grafting Solution: 10% NVP 
Average Average Graft Contact 
Pre-Soak Dose Rate Total Dose 
Thickness 
Angle 
Conditions (rads/min.) 
(Mrad) (.mu.m) 
(.degree.) 
______________________________________ 
None 16,000 0.144 .ltoreq.1 
24 
20% NVP/60.degree. C./ 
16,000 0.144 6 21 
90 min. 
None 5,129 0.135 .ltoreq.1 
25 
20% NVP/60.degree. C./ 
5,129 0.135 7 22 
90 min. 
______________________________________ 
No graft could be visualized by staining on the sample with no pre-soak, 
which indicates that the penetration depth is one micron or less. However, 
surface hydrophilicity is achieved as noted by the low contact angle 
values. This experiment demonstrates the feasibility of using higher dose 
rates and commercial irradiation facilities for large scale surface 
modification.