Chronic periodontal disease affect the tissues supporting around the teeth like gingival tissue, connective tissue, alveolar bone and periodontal ligaments. Hitherto, periodontal treatment was targeted to selectively repopulate the defect site with cell that has capability to regenerate lost tissue by promoting the concept of guided tissue regeneration but it requires second surgery due to non- biodegradability. The use of polymeric biodegradable nanofibrous coated scaffold that have the ability to deliver bioactives required for regeneration to occur is relatively a newer concept. The functionalization of polymeric scaffold with Bromelain and magnesium doped hydroxyapatite nanoparticle enhanced the mechanical, physico-chemical, thermal and biological properties of the scaffold by imitating the intricate extracellular matrix (ECM) architecture which provided the necessary bioactive cues that offered control over cellular functions by showing antibacterial potential, hemocompatibility and increasing the proliferation and migration rate in vitro. In addition, in ovo chicken chorioallantoic membrane assay and ex vivo aortic ring assay confirmed the efficacy of the developed scaffold by encouraging angiogenesis required for maintaining its viability after implanting onto the infected area. Further, the scaffold positively interacted with the host and actively contributed to the process of tissue regeneration in vivo in Wistar rat model.