The development, maintenance of healthy bone and regeneration of injured tissue in the human body comprise a set of intricate and finely coordinated processes. However, an analysis of current bone regeneration strategies shows that only a small fraction of well-reported bone biology aspects has been used as inspiration and transposed into the development of therapeutic products. Specific topics that include inter-scale bone structural organization, developmental aspects of bone morphogenesis, bone repair mechanisms, role of specific cells and heterotypic cell contact in the bone niche (including vascularization networks and immune system cells), cell-cell direct and soluble-mediated contact, extracellular matrix composition (with particular focus on the non-soluble fraction of proteins), as well as mechanical aspects of native bone will be the main reviewed topics. In this Review we suggest a systematic parallelization of (i) fundamental well-established biology of bone, (ii) updated and recent advances on the understanding of biological phenomena occurring in native and injured tissue, and (iii) critical discussion of how those individual aspects have been translated into tissue regeneration strategies using biomaterials and other tissue engineering approaches. We aim at presenting a perspective on unexplored aspects of bone physiology and how they could be translated into innovative regeneration-driven concepts.

Elysia crispata (Sacoglossa, Gastropoda) is a tropical sea slug known for its ability to incorporate functional chloroplasts from a variety of green macroalgae, a phenomenon termed kleptoplasty. This sea slug, amenable to laboratory cultivation, produces mucus, a viscous secretion that serves diverse purposes including protection, locomotion, and reproduction. In this study, we profiled the antimicrobial, antioxidant, and anti-inflammatory activities of the mucus of this sea slug. Results revealed inhibitory activity against several bacterial strains, more pronounced for Gram–negative bacteria. Particularly interesting was the strong inhibitory effect against Pseudomonas aeruginosa, a bacterial species classified by the WHO as a high-priority pathogen and associated with high-risk infections due to its frequent multidrug-resistant profile. Similar inhibitory effects were observed for the mucus native protein extracts, indicating that proteins present in the mucus contributed significantly to the antimicrobial activity. The mucus also showed both antioxidant and anti-inflammatory activities. The latter activities were associated with the low molecular weight (<10 kDa) fraction of the mucus rather than the native protein extracts. This study opens the way to further research on the biotechnological applications of the mucus secreted by this unique marine organism, particularly as an antimicrobial agent.

A handful of sea slugs of the order Sacoglossa are able to steal chloroplasts—kleptoplasts—from their algal food sources and maintain them functionally for periods ranging from several weeks to a few months. In this study, we investigated the role of kleptoplast photosynthesis on mucus production by the tropical sea slug Elysia crispata. Animals reared for 5 weeks in quasi dark (5 μmol photons m⁻² s⁻¹) showed similar growth to those under regular light (60–90 μmol photons m⁻² s⁻¹), showing that kleptoplast photosynthesis was not relevant for growth when sea slugs were fed ad libitum. However, when subjected to short-term desiccation stress, animals reared under regular light produced significantly more mucus. Furthermore, the carbohydrate content of secreted mucus was significantly lower in slugs limited in the photosynthetic activity of their kleptoplasts by quasi-dark conditions. This study indicates that photosynthesis supports the synthesis of protective mucus in kleptoplast-bearing sea slugs.

Some Sacoglossa sea slugs are capable of stealing and maintaining functional intracellular chloroplasts—kleptoplasts—from their macroalgal prey for periods of up to several months, a process known as kleptoplasty. Although the cultivation of these marine invertebrates under laboratory conditions is crucial for research in various fields (e.g., endosymbiosis, animal physiology, discovery of new marine natural products), rearing protocols are scarce. This study presents a standardized protocol for the laboratory rearing of large numbers of the sacoglossan tropical sea slug Elysia crispata. The detailed protocol successfully facilitated embryonic development, larval metamorphosis, and juvenile-to-adult transition, allowing the rearing of multiple generations. Two groups, characterized by acquiring different kleptoplasts, were obtained by feeding the sea slugs with two different prey macroalgae: Bryopsis sp. and Acetabularia acetabulum. Usually referred to as lettuce sea slug among marine aquarium hobbyists, E. crispata is a highly valued organism for its striking appearance and ability to control nuisance algal growth in reef aquariums. This protocol allows experimental reproducibility and access to specimens under different development stages, potentially boosting research on kleptoplasty while also contributing to reducing the impact of the marine aquarium trade on natural populations.

Elysia crispata is a sacoglossan sea slug that retains intracellular, functional chloroplasts stolen from their macroalgal food sources. Elysia crispata juveniles start feeding on the algae following metamorphosis, engulfing chloroplasts and turning green. In laboratory-reared animals, we report one juvenile “albino” specimen unable to retain chloroplasts. Within 6 weeks post-metamorphosis, the aposymbiotic sea slug was significantly smaller than its chloroplast-bearing siblings. This evidence highlights that chloroplast acquisition is required for the normal development of E. crispata.