Divergent effects of premineralization and prevascularization on osteogenesis and vascular integration in humanized tissue engineered bone constructs
Notice bibliographique
Résumé
Osteogenesis (bone formation) and vascularization (blood vessel formation) are two central and interconnected physiological-relevant processes in bone formation. Prevascularization of humanized tissue-engineered bone constructs (hTEBCs) has been proposed to better mimic the human bone microenvironment by enhancing vascular integration and facilitating greater osteogenic capacity. Here, we investigated the effects of premineralization and prevascularization on bone and vasculature development in an ectopic hTEBC model using a scaffold-hydrogel composite approach. Human osteoblast cells (hOBs) were cultured under osteogenic conditions (OM), with or without a 3-day mineralization boost (OM+) period for 4 weeks prior to implantation in vivo in a supporting porous polycaprolactone (mPCL) scaffold. Separately, photocrosslinkable fish gelatin-derived hydrogels placed within supporting mPCL scaffolds showed formation of elongated vascular networks as early as day 3 with in vitro coculture of human umbilical vein endothelial cells (HUVECs) and human bone marrow mesenchymal stem/stromal cells (MSCs). The OM and OM+ cultured constructs were subcutaneously implanted into immunocompromised rats with and without the prevascular hydrogels, resulting in four subgroups: OM, OM+, OM/Vas, and OM+/Vas. Our results demonstrated that the OM+ group led to more rapid osteoinduction and enhanced osteogenic differentiation in vivo with woven bone structure and active remodeling. Conversely, prevascularization (OM/Vas, OM+/Vas groups) led to reduce in vivo bone volume and density but promoted the development of human endothelial networks and successful anastomosis with host vasculature. Our study highlights the distinct contributions of premineralization and prevascularization, where premineralization is critical for robust bone formation and prevascularization enhances vascular integration, providing important insights for advancing the physiological relevance of hTEBC models in animal hosts. STATEMENT OF SIGNIFICANCE: This study demonstrates the development of humanized tissue engineered bone constructs incorporating a vascular niche using a rat. By integrating innovative premineralization and prevascularization techniques within scaffold-hydrogel composites, we show that premineralization accelerates bone formation, while prevascularization promotes endothelial network formation and integration with host vasculature. Photocrosslinkable, low-stiffness LunaGel™ hydrogels enhanced microcapillary-like structure formation and endothelial sprouting in in vitro co-culture. However, by combining osteogenic and vascular cues within a biodegradable composite, this work advances the bone tissue engineering field by creating a model that more accurately reflects the divergent and competing nature of vascularization and bone formation. This platform has broad applicability for studying bone-vascular interactions and may inform strategies to improve the design of biomaterials for regenerative therapies.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».