Mimicking nature by codelivery of stimulant and inhibitor to create temporally stable and spatially restricted angiogenic zones

Abstract

Nature frequently utilizes opposing factors to create a stable activator gradient to robustly control pattern formation. This study employs a biomimicry approach, by delivery of both angiogenic and antiangiogenic factors from spatially restricted zones of a synthetic polymer to achieve temporally stable and spatially restricted angiogenic zones in vivo. The simultaneous release of the two spatially separated agents leads to a spatially sharp angiogenic region that is sustained over 3 wk. Further, the contradictory action of the two agents leads to a stable level of proangiogenic stimulation in this region, in spite of significant variations in the individual release rates over time. The resulting spatially restrictive and temporally sustained profiles of active signaling allow the creation of a spatially heterogeneous and functional vasculature.controlled drug delivery | peripheral ischemia | VEGF antibody | diffusion reaction | Turing pattern

Therapeutic Approaches to the Regulation of Wound Angiogenesis

“…Three target articles [16][17][18] reviewed here investigated aspects of experimental regulation of wound angiogenesis (Table 1). A common thread is the exogenous application of bio-active molecules to a healing wound, with each method somehow utilizing or modifying VEGF biology to achieve specific angiogenic phenotypes in animal models.…”

Regenerative medicine: Current therapies and future directions

“…Providing a sequence of angiogenic factors that first initiate and then promote maturation of newly formed vessels can yield more functional networks (74) (Fig. 2 B and C), and mimicking development via delivery of both promoters and inhibitors of angiogenesis from distinct spatial locations can create tightly defined angiogenic zones (75).…”

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

“…Tight spatial regulation often results from the combined action of stimulatory and inhibitory factors. 144 Yuen et al 144 employed a dual-release system based on a poly(lactic-co-glycolic acid) (PLG) scaffold incorporating layers loaded with angiogenic stimulatory factor and inhibitory anti-VEGF. This led to a spatially sharp angiogenic region, sustained over 3 weeks.…”