Tissue repair requires a carefully orchestrated series of events, which, when disrupted, can lead to impaired healing and loss of function. Sustained delivery of growth factors can stimulate endogenous repair mechanisms; however, typical biomaterial delivery vehicles lack the ability to spatially and temporally control in vivo protein presentation. In order to improve the clinical delivery of bone morphogenetic protein-2 (BMP-2) for bone regeneration, we developed heparin-based microparticles that harness the natural binding affinity between heparin and BMP-2. Heparin microparticles provide effective, local presentation of BMP-2 within femoral bone defects in rats, leading to robust healing and improved spatial localization of bone formation.