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Many approaches have been made toward the development of scaffolds with good biocompatibility and appreciable physicochemical properties to facilitate stem cell adhesion, osteogenic differentiation, and vascularization in tissue engineering. Nowadays, vascularization is a main bottleneck in tissue engineering strategies that is needed to be overcome and developed. Herein, we construct a series of polyhedral oligomeric silsesquioxane (POSS)-modified porous gelatin hydrogels with different POSS concentrations from 0 to 5 wt %, defined as X % POSS hydrogels ( X = 0, 1, 2, 3, 4, 5) to support vascularized bone repair. The introduction of POSS into gelatin effectively promoted adhesive protein adsorption and integrin α5β1 expression, subsequently leading to enhanced adhesion of both rat bone marrow mesenchymal stem cells and human umbilical vein endothelial cells (HUVECs). In vitro experiments further demonstrated that POSS-containing hybrid hydrogels more effectively support the angiogenic tube and network formation in HUVECs than the 0% POSS hydrogel. Besides, POSS-containing hybrid hydrogels showed desirable performance as a sustained release system of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2), and they further accelerated vascular network establishment and the formation of a new bone in defect regions. When the hydrogels were implanted into critical-sized rat calvarial defects in vivo, the VEGF/BMP-2-coupled 3% POSS group gained a higher blood vessel volume in the bone defect regions (5.49 ± 0.35 mm 3 ) than the 3% POSS group (3.12 ± 0.20 mm 3 ) and the 0% POSS group (1.57 ± 0.25 mm 3 ), suggesting that the 3% POSS hydrogel with VEGF/BMP-2 would expedite vascularization. Based on these evaluations, our results indicated that the POSS-incorporated gelatin hydrogel would provide a promising bone graft scheme in potential clinical application of large bone defect repair.

Bone tissue engineering based on stem cells, growth factors and bioactive scaffolds presents an appealing but challenging approach for rehabilitation of patients with bone defects. A versatile system with the capability for easy operation and precise protein delivery in specific locations is attractive for enhancing bone regeneration. Here, we develop a non-invasive delivery system based on injectable and self-healing nanocomposite hydrogels for sustained protein release, which has the potential to improve the current orthopedic strategy. Specifically, LAPONITE® (LAP) nanoplatelets are able to accelerate the gelation process through hydrogen bonds with polysaccharide matrices, endowing hydrogels with superior mechanical and rheological behaviors, along with better injectability and self-healing ability. Attractively, the strong static binding between LAP nanoplatelets and bone morphogenetic protein-2 (BMP-2) can form stable LAP@BMP-2 complexes. The results indicate that the complexes effectively preserve the intrinsic bioactivity of BMP-2 and prolong the release period for more than four weeks. Moreover, hydrogels incorporating with the LAP@BMP-2 complexes synergistically boost cell spreading, proliferation activity and osteogenesis, both in vitro and in vivo, compared with LAP or BMP-2 alone. Overall, this study proposes a valid platform for protein therapeutics and non-invasive bone repair.

Stem cell therapy based on advanced biomaterials provides a promising strategy in bone tissue engineering. Nevertheless, guided bone regeneration which fulfills the criteria in terms of biomechanics, biodegradability and bioactivity is highly appealing but challenging. Inspired by the superior double-network (DN) structure, herein, a biodegradable hybrid DN hydrogel is proposed to promote in situ bone regeneration. The DN hydrogel is constructed by interspersing a methacrylated gelatin (GelMA) network into a well-defined nanocomposite (NC) hydrogel consisting of methacrylated chitosan (CSMA) and polyhedral oligomeric silsesquioxane (POSS) via a two-step photo-crosslinking process. The hybrid DN hydrogel has the following advantageous characteristics: (i) it exhibits enhanced stiffness and toughness benefiting from the inorganic POSS units and unique energy dissipation; (ii) naturally occurring biomacromolecules (chitosan and gelatin) as the hydrogel framework result in an appropriate biodegradation behavior, which can be replaced by newly formed tissues; (iii) it preferentially guides mesenchymal stem cells (MSCs) toward osteogenic differentiation in vitro by detecting the elevated levels of enzyme activity and calcium deposition along with the up-regulated osteogenesis-related genes and proteins; and (iv) accelerated in situ bone regeneration is observed after implanting MSC-loaded hydrogels into rat calvarial defects. Therefore, we provide a new insight to develop functional hydrogels for triggering specific cellular responses toward stem cell therapy and bone-related tissue engineering.

Mingjiao Chen and Meng Zhou contributed equally to this work B Retraction Note: Stem Cell Research & Therapy (2021) 12:85 b https://doi.org/10.1186/s13287-021-02154-7 The authors have retracted this article. Meng Zhou, Yao Fu and Zi Wang agree to this retraction. [Extracted from the article]