Critical-sized bone defects caused by traumatic fractures, tumour resection, and congenital malformation are unlikely to heal spontaneously. Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts. In this study, we developed an innovative bone engineering scaffold based on gelatin methacrylate (GelMA) hydrogel, obtained via a two-step procedure: first, solid lipid nanoparticles (SLNs) were loaded with resveratrol (Res), a drug that can promote osteogenic differentiation and bone formation; these particles were then encapsulated at different concentrations (0.01%, 0.02%, 0.04%, and 0.08%) in GelMA to obtain the final Res-SLNs/GelMA scaffolds. The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration in rat cranial defects were evaluated using various characterization assays. Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs, with the ideally slow and steady release of Res; the optimal scaffold was 0.02 Res-SLNs/GelMA. Therefore, the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility, osteoconduction, and osteoinduction, thereby showing potential for application in bone tissue engineering.

BACKGROUND: Degeneration of the annulus fibrosus (AF), an important structure of the intervertebral disc, is one of the main causes of degenerative disc disease. Fabrication of scaffolds replicating the stratified microstructure of the AF is critical for the successful regeneration of AF. METHODS: In this study, we cultured rabbit AF-derived stem cells (AFSCs) using fabricated electrospun fibrous poly-Llactic acid scaffolds with different diameters. We applied cyclic tensile strain (CTS) on the scaffolds to regulate the differentiation of AFSCs into specific cell types that resided at the inner, middle, and outer zones of the AF. RESULTS: We found that the morphologies of AFSCs on the smaller-fiber-diameter scaffolds were nearly round, whereas spindle-like cells morphologies were observed on large-diameter scaffolds. CTS enhanced these phenomena and made the cells slender. The expression levels of collagen-I in cells increased as a function of the fiber diameter, whereas collagen-II and aggrecan exhibited opposite trends. Moreover, the application of CTS upregulated the gene expressions of collagen-I, collagen-II, and aggrecan. CONCLUSION: Overlaying the scaffolds with different CTS-stimulated cells could eventually lead to engineered AF tissues with hierarchical structures that approximated the native AF tissue. Thus, the proposed methodologies could be potentially applied for AF regeneration.

Bone defects are a persistent challenge in clinical practice. Although repair therapies based on tissue-engineered materials, which are known to have a crucial role in defective bone regeneration, have gathered increased attention, the current treatments for massive bone defects have several limitations. In the present study, based on the immunomodulatory inflammatory microenvironment properties of quercetin, we encapsulated quercetin solid lipid nanoparticles (SLNs) in a hydrogel. Temperature-responsive poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA) modifications were coupled to the main chain of hyaluronic acid (HA) hydrogel, constructing a novel, injectable bone immunomodulatory hydrogel scaffold. Extensive in vitro and in vivo data showed that this bone immunomodulatory scaffold forms an anti-inflammatory microenvironment by decreasing M1 polarization, while elevating the M2 polarization. Synergistic effects on angiogenesis and anti-osteoclastic differentiation were observed. These findings further proved that administering quercetin SLNs encapsulated in a hydrogel can aid bone defect reconstruction in rats, providing new insights for large-scale bone defect repair.

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