Sustainable Valorization of Biogenic Waste for Bone Repair and Regeneration: A Comprehensive Review of Eggshell and Aquatic Biomaterials.

Bone loss represents a significant clinical burden that has driven the development of improved orthopedic graft substitutes. Although current grafting options, including autografts, allografts, and xenografts, have demonstrated considerable therapeutic potential, their widespread application is constrained by limitations such as donor scarcity, limited availability, and associated clinical risks. Consequently, biologically derived materials, including avian eggshells and marine bivalve shells, have emerged as promising alternative sources to produce bone precursor materials and next-generation bone graft substitutes. This review summarizes recent advances in avian eggshell- and marine shell-derived calcium carbonate (CaCO3) materials for bone regeneration and examines their preclinical evaluation in diverse animal models, including critical-size defects in calvarial, femoral, radial and mandibular bone. Relevant studies published over the past ten years were systematically analyzed, focusing on natural calcium carbonate systems derived from avian eggshell and marine shells, including oyster, mussel, clam, scallop, cockle, and sea urchins. A structured literature search was conducted using PubMed, Scopus, and Google Scholar to identify studies published between 2015 and 2025 investigating eggshell- and aquatic-derived biomaterials for bone repair and regeneration. Eligible studies were screened, and data were comparatively analyzed with respect to biomaterial source, scaffold fabrication, physicochemical characteristics, mechanical performance, biocompatibility, osteogenic potential, and the use of preclinical animal studies. Eggshell-derived biomaterials currently show the strongest translational evidence, while aquatic shell-derived biomaterials remain promising but underexplored for bone regeneration. Furthermore, this review critically examines the scientific, manufacturing, and regulatory challenges that must be addressed before clinical implementation.