Aug 2026· iScience· Vol 29, pp. 117200· 0 citations· 58 references
Medicine
TL;DR
It is suggested that gradient nHA-loaded CMCS hydrogels can effectively enhance osteogenesis and support bone regeneration.
Abstract
Summary Large bone defects remain a clinical challenge due to limited regenerative capacity. In this study, carboxymethyl chitosan (CMCS) hydrogels incorporating gradient nano-hydroxyapatite (nHA) were developed to enhance bone repair. The composite hydrogels exhibited improved mechanical properties, controlled degradation, and good biocompatibility. In vitro, nHA-containing hydrogels promoted bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation, as shown by increased alkaline phosphatase (ALP) activity, mineralization, and upregulation of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and bone morphogenetic protein-2 (BMP-2). In vivo, implantation in a rat distal femoral condyle defect model showed enhanced new bone formation and improved trabecular structure, particularly in the 1% nHA group. These results suggest that gradient nHA-loaded CMCS hydrogels can effectively enhance osteogenesis and support bone regeneration.
Critical-sized bone defects (CSDs) represent a major clinical challenge due to their limited self-healing capacity. Conventional hydrogels incorporating crystalline hydroxyapatite (HA) often fail to recapitulate the hierarchical nanostructure of native bone, leading to suboptimal regeneration outcomes. To overcome this, we developed a biomimetic hydrogel by molecularly integrating amorphous calcium phosphate oligomers (CPO) into gelatin methacryloyl (GelMA), enabling a bone-like organic-inorganic hybrid network. This composite exhibits outstanding performance: an ultimate strength of 192 kPa at 18 wt% CPO confirms robust mechanical reinforcement, while 54% mass retention after 56 days underscores exceptional degradation resistance and dose-dependent bioactivity, evidenced by a two-fold upregulation of alkaline phosphatase (ALP) activity. The amorphous CPO facilitates biomimetic HA nucleation within the GelMA matrix, mimicking the natural mineralization process. In a rat calvarial CSD model, the hydrogel promoted 60% bone volume regeneration within 12 weeks, significantly outperforming conventional composites, through seamless host integration, vascularized trabecular bone formation, and a collagen-mineral hierarchy resembling native osteogenesis. This study establishes CPO as a transformative component that converts passive scaffolds into bioactive osteogenic microenvironments, offering a clinically viable strategy for complex bone regeneration.
Yue Shu, Meizi Zhang, Bo Li et al.· Journal of Biomedical Materi...· 0 citations
Osteoporosis is characterized by progressive bone loss and structural deterioration caused by an imbalance between bone resorption and formation. Although mesenchymal stem cells (MSCs) possess strong osteogenic potential, their therapeutic use is limited by poor retention, low survival, and insufficient maturation after direct injection. Here, we report an injectable, self-healing polysaccharide hydrogel designed to enhance MSC delivery and osteogenic differentiation for bone regeneration. The hydrogel forms through dynamic Schiff-base crosslinking between succinylated chitosan and aldehyde-modified hyaluronic acid, enabling rapid in situ gelation, uniform cell encapsulation, and structural recovery after mechanical disruption. The system exhibits tunable mechanical properties compatible with osteogenic mechanotransduction. Encapsulated MSCs maintained high viability, formed spheroid-like structures, and showed accelerated osteogenic maturation, evidenced by increased alkaline phosphatase activity, enhanced mineral deposition, and upregulation of osteoblast and osteocyte markers. Notably, the hydrogel microenvironment promoted osteogenic commitment even without differentiation supplements. These findings demonstrate that the hydrogel provides a mechanically instructive and biologically supportive environment for MSC-mediated bone regeneration and represents a promising minimally invasive strategy for osteoporotic bone repair.
Jacob Beitzel, Xiaojie Lin, Yang Zhou et al.· ACS Applied Bio Materials· 0 citations
To address alveolar bone defects and the limitations of conventional grafts, tissue-engineered scaffolds have emerged as a promising alternative. Carboxymethyl chitosan (CMC) is a biocompatible and biodegradable polysaccharide with potential for bone regeneration; however, its brittleness and poor mechanical strength restrict its application. Here, we developed CMC-reduced graphene oxide (rGO) composite scaffolds with rGO concentrations of 0%, 0.5%, 1%, and 2% to overcome these drawbacks. The scaffolds were systematically characterized for their morphological, crystallographic, spectroscopic, and biomechanical properties, as well as their in vitro cytocompatibility and in vivo osteogenic performance. The incorporation of rGO enhanced structural homogeneity, optimized pore architecture, and significantly improved mechanical strength in a concentration-dependent manner, with tensile strength increasing from 1.64 to 8.13 MPa and elastic modulus from 1.14 to 25.05 MPa. In vitro, when MC3T3-E1 cells were grown in osteogenic medium, scaffolds loaded with 0.5%-1% rGO led to better cell survival and higher ALP activity-both pointing to stronger osteogenic differentiation. The 2% rGO scaffolds, however, turned out to be toxic to cells. Structural analyses confirmed the preservation of CMC crystallinity and revealed hydrogen bonding between rGO and CMC, elucidating the reinforcement mechanism. In a rat cranial defect model, the 1% rGO scaffold group demonstrated superior new bone formation, mineralization, and trabecular maturation. These findings underscore the dual function of rGO in simultaneously improving the mechanical integrity and osteogenic capacity of CMC-based scaffolds, with 0.5%-1% rGO identified as the optimal concentration window for bone tissue engineering applications.
Ronghui Zhou, Yanjun Lin, Xiaojing Zhu et al.· Journal of Biomedical Materi...· 0 citations
Conventional gelatin (Gel) and alginate hydrogels possess excellent biocompatibility. Their high water content and three-dimensional porous structure mimic the extracellular matrix, facilitating nutrient transport and metabolic waste removal. However, their application in bone tissue engineering is hindered by insufficient mechanical strength, rapid degradation, and weak osteogenic activity. In this study, we developed a self-cross-linking hydrogel (GOP hydrogel) reinforced with calcium phosphate oligomers (CPO). The network was formed via a Schiff base reaction between periodate-oxidized sodium alginate (OSA) and gelatin, with small-sized CPO acting as an inorganic cross-linker to enhance intermolecular bonding and strengthen the polymeric network. The composite hydrogel was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD), and its mechanical properties, degradation behavior, and swelling capacity were evaluated. The GOP hydrogel exhibited excellent biocompatibility, supported cell viability and osteogenic differentiation, and promoted vascularized healing in critical-sized calvarial defects in rats. With the incorporation of CPO, the hydrogels exhibited enhanced mechanical strength, regulated degradation and swelling, and improved mineralization and osteogenic activity. These findings indicate that the GOP hydrogel meets the key requirements for bone tissue engineering scaffolds and holds considerable promise for bone regeneration applications.
Lingfei Liu, Ke Li, Ziyi Yan et al.· ACS Applied Bio Materials· 0 citations
The bioactive chitosan/Mg-HAp nanocomposite scaffold effectively promotes bone regeneration by enhancing osteogenic signaling pathways and exhibits strong potential for bone tissue engineering applications.
S.M. Hefzollesan, H. Musayeva, Hamed Aghazadeh et al.· Emergent Materials· 0 citations
This review critically examines recent advances in the development and application of HAp–hydrogel composites for cartilage regeneration, highlighting material design principles, fabrication strategies, healing mechanisms, and the key challenges that continue to influence their clinical translation.