Green technologies for the derivation of bioactive compounds from sea cucumber (Cucumaria frondosa) by-products and the subsequent development of gel platforms for biomedical purposes

Abstract

The Atlantic sea cucumber, Cucumaria frondosa, generates substantial processing by-products that remain underutilized despite being rich in bioactive compounds and functional biopolymers. This dissertation establishes an integrated marine biorefinery framework that couples green sequential extraction with biomaterial engineering to valorize C. frondosa viscera into both high-value extracts and marine-derived delivery platforms, advancing circular marine bioprocessing for biomedical applications. Supercritical carbon dioxide (scCO2) was employed as a green solvent-based pretreatment to recover lipid fractions and enhance downstream accessibility of polar constituents. Subsequent extractions using ethanol (EtOH) and water significantly improved saponin recovery while preserving antioxidant activity. Sequential scCO2 extraction followed by a 24-hour extraction with 70% EtOH achieved saponin yields of 16.26 ± 2.47 mg OAE/g, comparable to the conventional hexane defatting-ultrasonic extraction (17.31 ± 0.60 mg OAE/g), while coupled 24-hour hot-water extraction yielded 12.99 mg OAE/g, demonstrating that scCO2-assisted sequential extraction provides an efficient and environmentally favourable alternative for saponin isolation. The residual biomass was further repurposed into sea cucumber polysaccharide crudes (SCPSC), which served as a marine-derived structural precursor for gel fabrication. To establish a scalable, crosslinker-free gelation platform, injectable and self-healing polyelectrolyte complex (PEC) hydrogels were developed using chitosan, marine chondroitin sulphate or algal fucoidan, hydrolyzed collagen, and cellulose nanocrystals (CNC). These physically crosslinked networks exhibited tunable swelling (~178-766%), low E-factors down to 0.98, and solid-like rheological behaviour (G' ≫ G"), with mesh sizes of ~5-10 nm and strength modulated through formulation control. Building on this framework, chitosan/SCPSC/CNC/sodium dodecyl sulfate (SDS)-based PEC porous networks were prepared via a semi-dissolution acidification sol-gel transition (SD-A-SGT) followed by poor-solvent-induced aggregation. Despite the compositional heterogeneity of the crude extracts, the resulting organogels formed robust physically crosslinked networks, as evidenced by G' ≫ G", with no crossover between 25 and 50 °, rubbery plateau moduli reaching ~30 kPa, and compressive Young’s moduli up to 18.36 kPa. Equilibrium swelling ratios ranged from ~170 to 770%, with CNC-reinforced formulations typically reaching ~290-350%, while low SDS-containing organogels showed exceptional uptake (~770%) driven by electrostatic chain expansion. Controlled solvent exchange and drying converted these organogels into aerogels and structure-preserving hexane-exchanged xerogels with tunable architectures and functions. Using curcumin as a hydrophobic model payload, the dried gels achieved encapsulation efficiencies up to 45.56 ± 5.37% and loading capacities up to 41.92 ± 3.85 mg/g, while densified conventional xerogels reached a maximum apparent loading of 45.91 ± 4.19 mg/g. Structural and thermal analyses confirmed suppression of curcumin crystallinity via nanoconfinement within the porous matrices. In vitro release studies demonstrated architecture-dependent kinetics, with aerogels reaching ~94% cumulative release within 24 h, compared with ~73% for densified xerogels, enabling tunable burst-to-sustained delivery profiles. Encapsulation also markedly improved curcumin stability against light and heat relative to free curcumin.