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Injectable hydrogels can fill irregular defects and promote in situ tissue regrowth and regeneration. The ability of directing stem cell differentiation in a three-dimensional microenvironment for bone regeneration remains a challenge. In this study, we successfully nanoengineer an interconnected microporous networked photocrosslinkable chitosan in situ-forming hydrogel by introducing two-dimensional nanoclay particles with intercalation chemistry. The presence of the nanosilicates increases the Young’s modulus and stalls the degradation rate of the resulting hydrogels. We demonstrate that the reinforced hydrogels promote the proliferation as well as the attachment and induced the differentiation of encapsulated mesenchymal stem cells in vitro. Furthermore, we explore the effects of nanoengineered hydrogels in vivo with the critical-sized mouse calvarial defect model. Our results confirm that chitosan-montmorillonite hydrogels are able to recruit native cells and promote calvarial healing without delivery of additional therapeutic agents or stem cells, indicating their tissue engineering potential. Injectable hydrogels could be used to repair bone defects. Here the authors incorporate nanoclay particles into chitosan creating an interconnected microporous hydrogel and show that this hydrogel can support MSC proliferation and differentiation in vitro, and support the recruitment of native cells and bone regeneration in a mouse calvarial defect model.

Background Demineralized bone matrix (DBM), an allograft bone processed to better expose osteoinductive factors such as bone morphogenetic proteins (BMPs), is increasingly used for clinical bone repair. However, more extensive use of DBM is limited by its unpredictable osteoinductivity and low bone formation capacity. Commercial DBM products often employ polymeric carriers to enhance handling properties but such carriers generally do not possess bioactive functions. Heparin is a highly sulfated polysaccharide and is shown to form a stable complex with growth factors to enhance their bioactivities. In this study, a new heparinized synthetic carrier for DBM is developed based on photocrosslinking of methacrylated glycol chitosan and heparin conjugation. Results Heparinized chitosan exerts protective effects on BMP bioactivity against physiological stressors related to bone fracture healing. It also enhances the potency of BMPs by inhibiting the activity of BMP antagonist, noggin. Moreover, heparinized chitosan is effective to deliver bone marrow stromal cells and DBM for enhanced osteogenesis by sequestering and localizing the cell-produced or DBM-released BMPs. Conclusions This research suggests an essential approach of developing a new hydrogel carrier to stabilize the bioactivity of BMPs and improve the clinical efficacy of current bone graft therapeutics for accelerated bone repair.

Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics.

Identifying sparse, context-dependent target discourse such as ethical risk discourse on generative AI in noisy social media data is a long-standing challenge in computational text analysis. Beyond classification, interpreting the resulting topic structure transparently poses an additional methodological challenge. To address these problems, this study proposes a reproducible two-stage framework. First, four LLMs (GPT-4.1, GPT-3.5-turbo, Claude Sonnet 4.6, and Gemini 2.5 Pro) are compared on a human-annotated validation set using a zero-shot prompt grounded in five ethical risk categories, and the best-performing model is selected to classify the full keyword-prescreened corpus. Validity is evaluated against human annotations and supervised baselines. Second, BERTopic is applied to the classified corpus, and sub-topics are linked to higher-level categories through an explicit mapping protocol. The study draws on approximately 500,000 ChatGPT-related English-language tweets from January to March 2023. Only 36.4% of the validation sample constituted ethical risk discourse, confirming substantial pre-screening noise. GPT-4.1, selected as the final classification model, achieved the strongest performance (accuracy = 0.899, F1 = 0.859, Cohen’s κ = 0.780), significantly outperforming conventional supervised baselines. BERTopic yielded 33 non-outlier sub-topics; within this subset, Societal and democratic risks (36.16%) and Technical safety (20.90%) were the largest categories. These findings should be interpreted not as a direct measure of users’ risk perceptions in 2023, but as the category distribution within the structured subset excluding outliers, after keyword screening and classification under the current ethical risk taxonomy used in this study. Within this scope, societal and institutional concerns were at least as prominent as those related to technical failures.

Background: Unlike bone tissue, articular cartilage regeneration has not been very successful and has many challenges ahead. We have previously developed injectable hydrogels using photopolymerizable chitosan (MeGC) that supported growth of chondrocytes. In this study, we demonstrate a biofunctional hydrogel for specific use in cartilage regeneration by conjugating transforming growth factor- beta 1 (TGF- beta 1), a well-documented chondrogenic factor, to MeGC hydrogels impregnating type II collagen (Col II), one of the major cartilaginous extracellular matrix (ECM) components. Results: TGF- beta 1 was delivered from MeGC hydrogels in a controlled manner with reduced burst release by chemically conjugating the protein to MeGC. The hydrogel system did not compromise viability of encapsulated human synovium-derived mesenchymal stem cells (hSMSCs). Col II impregnation and TGF- beta 1 delivery significantly enhanced cellular aggregation and deposition of cartilaginous ECM by the encapsulated cells, compared with pure MeGC hydrogels. Conclusions: This study demonstrates successful engineering of a biofunctional hydrogel with a specific microenvironment tailored to promote chondrogenesis. This hydrogel system can provide promising efficacious therapeutics in the treatment of cartilage defects.

Background Unlike bone tissue, articular cartilage regeneration has not been very successful and has many challenges ahead. We have previously developed injectable hydrogels using photopolymerizable chitosan (MeGC) that supported growth of chondrocytes. In this study, we demonstrate a biofunctional hydrogel for specific use in cartilage regeneration by conjugating transforming growth factor-β1 (TGF-β1), a well-documented chondrogenic factor, to MeGC hydrogels impregnating type II collagen (Col II), one of the major cartilaginous extracellular matrix (ECM) components. Results TGF-β1 was delivered from MeGC hydrogels in a controlled manner with reduced burst release by chemically conjugating the protein to MeGC. The hydrogel system did not compromise viability of encapsulated human synovium-derived mesenchymal stem cells (hSMSCs). Col II impregnation and TGF-β1 delivery significantly enhanced cellular aggregation and deposition of cartilaginous ECM by the encapsulated cells, compared with pure MeGC hydrogels. Conclusions This study demonstrates successful engineering of a biofunctional hydrogel with a specific microenvironment tailored to promote chondrogenesis. This hydrogel system can provide promising efficacious therapeutics in the treatment of cartilage defects.

A hydrogel platform using visible light inducible methacrylated glycol chitosan and riboflavin, an aqueous initiator from natural vitamins is biocompatible and supports proliferation of the encapsulated cells. However, the hydrogel platform has limited cell-matrix interaction, relatively slow degradation, and poor ability to deliver growth factors, which may hinder tissue regeneration. Therefore, the objective of this research is to design a hydrogel system which mimics native extracellular microenvironments, provides tunable degradation, and stabilizes bioactivity of growth factors. The first study explores if the incorporation of native extracellular matrix components in chitosan hydrogel can promote cell-matrix interaction. The hydrogel is functionalized with cell adhesive motifs and cartilaginous or bony matrix. The modified hydrogels increase chondrogenic or osteogenic differentiation of the encapsulated cells by enhancing cell-matrix interaction. This work suggests a hydrogel platform with a specific microenvironment tailored to promote cell differentiation. Tuning hydrogel degradation enables effective and successful tissue regeneration by modulating cellular behaviors and matrix formation. A new degradable hydrogel system is developed based on a unique enzyme-substrate complex, lysozyme-chitosan. Incorporation of lysozyme accelerates hydrogel degradation in a dose dependent manner. This study proposes a novel strategy of incorporating an exogenous enzyme specific to the hydrogel which can control degradation kinetics in a cell-independent manner. Bacterial infection during surgical processes leads to serious complications and continuously results in unsuccessful wound repair. A lysozyme-chitosan conjugate not only allows tunable degradation, but also exhibits antimicrobial properties. The lysozyme modified hydrogels successfully inhibit bacterial growth and delay its proliferation. This work verifies an advanced hydrogel platform with dual functions, tunable degradability and anti-infection. Although heparin is widely used in controlled release system due to its strong binding ability and protective effect for growth factors such as bone morphogenetic protein-2 (BMP-2), it suffers from natural variability, difficulty in modification, and unknown physiological roles. Heparin mimetic sulfonated molecules can do a similar role of heparin by protecting BMP-2 against therapeutically relevant stressors and enhancing its bioactivity. This work demonstrates a new hydrogel system to improve clinical efficacy of BMP-2 and other heparin-binding growth factors. These findings suggest great potentials of material-based therapeutics for tissue engineering application.

Growth factor-based therapeutics using bone morphogenetic protein 2 (BMP-2) presents a promising strategy to reconstruct craniofacial bone defects such as mandible. However, clinical applications require supraphysiological BMP doses that often increase inappropriate adipogenesis, resulting in well-documented, cyst-like bone formation. Here we reported a novel complementary strategy to enhance osteogenesis and mandibular bone repair by using small-molecule phenamil that has been shown to be a strong activator of BMP signaling. Phenamil synergistically induced osteogenic differentiation of human bone marrow mesenchymal stem cells with BMP-2 while suppressing their adipogenic differentiation induced by BMP-2 in vitro. The observed pro-osteogenic and antiadipogenic activity of phenamil was mediated by expression of tribbles homolog 3 (Trb3) that enhanced BMP-smad signaling and inhibited expression of peroxisome proliferator-activated receptor gamma (PPARγ), a master regulator of adipogenesis. The synergistic effect of BMP-2+phenamil on bone regeneration was further confirmed in a critical-sized rat mandibular bone defect by implanting polymer scaffolds designed to slowly release the therapeutic molecules. These findings indicate a new complementary osteoinductive strategy to improve clinical efficacy and safety of current BMP-based therapeutics.

This dissertation theorizes corporate power and tests its impact on income inequality in the globalization context. Three related questions are addressed: First, is state coordination and labor unionism significant in attenuating the detrimental effect of neoliberal globalization on income inequality? Second, to what extent does corporate power mediate the positive/negative effects of global capitalism on income inequality? Last, what is the mechanism through which systematic inequality is institutionalized in high-income democracies? In answering these, corporate power is conceptualized as a compound of quantitative power, directly observable in markets, and qualitative power, indirectly manifested in the relational aspects (i.e. institutional arrangement and public support). I collected the data of 29 countries for a nine-year period, 2002-2008 from multiple databases, including the UNU-WIDER World Income Inequality, global corporations’ interlock data (Murray 2012, Carroll 2010), political institutional data of the World Bank, the OECD labor statistics, and the Economic Freedom of the World. This dissertation from a comparative historical approach combined qualitative and quantitative analyses. The main questions are examined in three steps: First, fixed effects models estimated the corporate power impact, controlling for unmeasured country-specific factors. Second, random effects models estimated the effects of corporate influence via neoliberal state coordination and the union on income inequality, controlling for socio-political variables. Third, based on the results from panel-data analyses, a case study of South Korea was conducted by implementing a process tracing method to confirm causal mechanisms. I found that neoliberal state coordination increases inequality while different degrees of transnational corporate power are conditional upon state coordination. Also, the negative effect of corporate power on inequality appeared significantly sizable in countries with corporations that are G500 listed, financially expanding, globally central and highly autonomous in labor regime. While the union density significantly ameliorates the detrimental effect of capitalist expansion, its effectiveness has been decreasing. These determinants for income inequality are explained by the patterns of finance capitalism, state coordination suspended by outgrowing private sector, and asymmetry in labor market between employers and employees. Taken together, this study shows to what extent and how neoliberalism facilitated institutionalization of corporate power, and aggravated income inequality.

The direct use of adipose‐derived stem cells (ASCs) alone has had limited success in the treatment of large bone defects. This study used an alternative approach that complements bone morphogenetic protein (BMP) activity to maximize the osteogenesis of ASCs by regulating levels of antagonists and agonists to BMP signaling. Findings indicate promising stem cell‐based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics. Although adipose‐derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP–Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite‐coated poly(lactic‐coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP‐based therapeutics. Significance Although stem cell‐based tissue engineering strategy offers a promising alternative to repair damaged bone, direct use of stem cells alone is not adequate for challenging healing environments such as in large bone defects. This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell‐based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics.