Enhancing integration of articular cartilage grafts via photochemical bonding

Abstract

The integration of osteochondral grafts to native articular cartilage is critical as the lack of graft integration may lead to continued tissue degradation, poor load transfer and inadequate nutrient transport. Photochemical bonding promotes graft integration by activating a photosensitizer at the interface via a light source and avoids negative effects associated with other bonding techniques. We hypothesized that the bond strength depends on photosensitizer type and concentration in addition to light exposure. Photochemical bonding was evaluated using methylene blue (MB), a cationic phenothiazine photosensitizer, and two phthalocyanine photosensitizers, Al(III) phthalocyanine chloride tetrasulfonic acid (CASPc) and aluminum phthalocyanine chloride (AlPc). Exposure was altered by varying irradiation time for a fixed irradiance or by varying irradiance with a fixed irradiation time. MB was ineffective at producing bonding at the range of concentrations tested while CASPc produced a peak twofold bond strength increase over controls. AlPc produced substantial bonding at all concentrations with a peak 3.9-fold bond strength increase over controls. Parametric tests revealed that bond strength depended primarily on the total energy delivered to the bonding site rather than the rate of light delivery or light irradiance. Bond strength persisted for 1 week of in-vitro culture, which warrants further exploration for clinical applications. These studies indicate that photochemical bonding is a viable strategy for enhancing articular cartilage graft integration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2406-2415, 2018.

Surgical and tissue engineering strategies for articular cartilage and meniscus repair

“…The removal of anti-adhesive glycosaminoglycans and the priming of engineered tissue with collagen crosslinking agents are promising strategies that have shown preliminary success towards improving implant integration. For example, chondroitinase ABC treatment of native articular cartilage plugs before they are press-fitted into an articular cartilage annulus resulted in an integrated assembly with interfacial shear strength of 0.135 MPa, compared with 0.068 MPa in the untreated control 164 . In another study, LOXL2 treatment of similar assemblies of engineered cartilage and native cartilage rings resulted in a 2.2-fold increase in interfacial stiffness 165 .…”

A Systematic Review and Guide to Mechanical Testing for Articular Cartilage Tissue Engineering

“…In the push-out scenario, used for testing cartilage or meniscus integration, a cylindrical punch is cored and replaced by a scaffold or construct and cultured for a duration of time to strengthen the interface. [82][83][84][85] The inner core is then pushed out of the outer core with an indenter, allowing for calculation of the integration strength. Another method for testing cartilage integration approaches involves lap-shear testing, [86][87][88] which is achieved by fixing each side of an interface to a substrate or clamping, and applying tension parallel to the adhesive interface.…”

Rapid and durable photochemical bonding of cartilage using the porphyrin photosensitizer verteporfin

“…Study conditions are summarized in Table I. Studies included a negative control group of samples that were digested and press-fitted but were not exposed to photosensitizer or illumination, and a positive control group treated with 5 mM AlPc and irradiated at 1.58 W/cm 2 for 10 min, conditions previously found to produce strong bonding 11 . In each substudy, cores and annuli were randomly allocated to experimental groups.…”

“…Early studies evaluated a patented 1e8, naphthalamide dye with a peak absorbance wavelength of 430 nm 9 . Subsequent studies examined photosensitizers activated by deep red light (660e690 nm) that penetrates deeper into the tissue 10,11 . In particular, aluminum phthalocyanine chloride (AlPc) was more effective than either a similar phthalocyanine, Al(III) phthalocyanine chloride tetrasulfinic acid (CASPc) or the cationic phenothiazine Methlyene Blue, achieving substantial bond strengths but requiring relatively high light irradiance and irradiation times on the order of 10 min 11 .…”

“…Subsequent studies examined photosensitizers activated by deep red light (660e690 nm) that penetrates deeper into the tissue 10,11 . In particular, aluminum phthalocyanine chloride (AlPc) was more effective than either a similar phthalocyanine, Al(III) phthalocyanine chloride tetrasulfinic acid (CASPc) or the cationic phenothiazine Methlyene Blue, achieving substantial bond strengths but requiring relatively high light irradiance and irradiation times on the order of 10 min 11 . Reduction of both light irradiance and irradiation time would improve the clinical feasibility of cartilage photochemical bonding, prompting a search for alternative photosensitizer agents.…”