Laser patterning of ECM-derived biomaterials to direct degradation, site-specific resorption, controlled vascularization and functional repair of large nerve defects.

Abstract

Controlled degradation of extracellular matrix-derived biomaterials in a site-specific and temporal sequence might facilitate early vascularization and improve tissue regeneration. In this study, we developed a tailored laser patterning treatment that successfully addresses this challenge. We show that application of a focused diode-pumped solid-state laser (532 nm) for 30 s duration leads to local heating and reduction of collagen fibril integrity in localized laser-patterned areas of a collagen biomaterial. When implanted in vivo, these thermally degraded regions then become susceptible to further in vivo degradation by inducing site-specific resorption. This allows unimpeded vascular ingrowth and accelerated recovery without prematurely compromising biomaterial structural integrity. Using peripheral nerve injury as an exemplar indication, we show that laser-treated collagen-based nerve guidance conduits (NGCs) have enhanced regenerative potential. Increased in vivo vascularization, in comparison to non laser-treated NGCs, was shown in both a chick chorioallantoic membrane and a rat critical-sized 15 mm sciatic nerve defect model. When nerve repair was assessed, laser-treated NGCs promoted aligned axonal growth and myelin sheath distribution resembling the native nerve, while also restoring nerve action potential to levels of a healthy nerve. This resulted in functional healing and successful nerve recovery as demonstrated by significantly reduced muscle atrophy. This straightforward yet innovative approach offers significant potential for enhancing functional nerve repair when utilizing collagen-based biomaterials but can also be applied to other natural polymer-based biomaterials to tailor degradation and vascularization for a myriad of indications. STATEMENT OF SIGNIFICANCE: A major challenge associated with implanted biomaterials is the limited control over biomaterial degradation, which can result in failure to adequately repair damaged tissues. In this study, we address this issue through the use of laser patterning which produces localized changes in the structure of extracellular matrix-based biomaterials in the form of depressions and changes in the biochemical composition which then accelerate in vivo biomaterial resorption as the depressions then develop into physical voids. This directs early cell infiltration and eventually vascularization into the biomaterial. At the same time, we show that site-specific resorption does not compromise overall material integrity and allows the implanted biomaterial to maintain its structure so as to facilitate new tissue formation at the injured site.