Transdermal photopolymerization for minimally invasive implantation

Abstract

Photopolymerizations are widely used in medicine to create polymer networks for use in applications such as bone restorations and coatings for artificial implants. These photopolymerizations occur by directly exposing materials to light in "open" environments such as the oral cavity or during invasive procedures such as surgery. We hypothesized that light, which penetrates tissue including skin, could cause a photopolymerization indirectly. Liquid materials then could be injected s.c. and solidified by exposing the exterior surface of the skin to light. To test this hypothesis, the penetration of UVA and visible light through skin was studied. Modeling predicted the feasibility of transdermal polymerization with only 2 min of light exposure required to photopolymerize an implant underneath human skin. To establish the validity of these modeling studies, transdermal photopolymerization first was applied to tissue engineering by using "injectable" cartilage as a model system. Polymer/chondrocyte constructs were injected s.c. and transdermally photopolymerized. Implants harvested at 2, 4, and 7 weeks demonstrated collagen and proteoglycan production and histology with tissue structure comparable to native neocartilage. To further examine this phenomenon and test the applicability of transdermal photopolymerization for drug release devices, albumin, a model protein, was released for 1 week from photopolymerized hydrogels. With further study, transdermal photpolymerization potentially could be used to create a variety of new, minimally invasive surgical procedures in applications ranging from plastic and orthopedic surgery to tissue engineering and drug delivery.

Figure 1

(A) Schematic of transdermal photopolymerization. (B) Penetration of light through swine skin at 360 (▴) and 550 nm (●) and human skin at 360 (▵) and 550 nm (○). (C) Kinetics of transdermal photopolymerization of PEODM with UVA (dashed line), visible light (solid line) and beneath 1.5 mm human skin by using UVA (dashed line) and visible light (solid line) with an incident light intensity of 100 mW/cm² and 0.04% (wt/wt) photoinitiator.

Figure 2

Normalized 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide absorbances of chondrocytes after exposure to 1.5 mW/cm² UVA light and HPK (% wt/vol). Control cells were not exposed to initiator or light, HPK control (0.036% HPK) was not exposed to light, and UVA control cells were exposed to light only.

Figure 3

(A) Total collagen and GAG contents (per construct wet weight) of chondrocytes encapsulated and implanted by transdermal photopolymerization. (B) Safranin O-stained histological section of neocartilage 6 weeks postimplantation (×200). (C) Hematoxylin/eosin-stained section of an implanted hydrogel (P, without cells), surrounded by a fibrous capsule (C), s.c. tissue and skin (S). (D) Release of BSA from PEODM (M_r 1,000) hydrogels over 200 hr.