Background: Cartilage injury and pathological degeneration are reported in millions of patients globally. Cartilages such as articular hyaline cartilage are characterized by poor self-regeneration ability due to lack of vascular tissue. Current treatment methods adopt foreign cartilage analogue implants or microfracture surgery to accelerate tissue repair and regeneration. These methods are invasive and are associated with the formation of fibrocartilage, which warrants further exploration of new cartilage repair materials. The present study aims to develop an injectable modified gelatin hydrogel. Method: The hydrogel effectively adsorbed proteoglycans secreted by chondrocytes adjacent to the cartilage tissue in situ, and rapidly formed suitable chondrocyte survival microenvironment modified by ε-poly-L-lysine (EPL). Besides, dynamic covalent bonds were introduced between glucose and phenylboronic acids (PBA). These bonds formed reversible covalent interactions between the cis−diol groups on polyols and the ionic boronate state of PBA. PBA-modified hydrogel induced significant stress relaxation, which improved chondrocyte viability and cartilage differentiation of stem cells. Further, we explored the ability of these hydrogels to promote chondrocyte viability and cartilage differentiation of stem cells through chemical and mechanical modifications. Results: In vivo and in vitro results demonstrated that the hydrogels exhibited efficient biocompatibility. EPL and PBA modified GelMA hydrogel (Gel-EPL/B) showed stronger activity on chondrocytes compared to the GelMA control group. The Gel-EPL/B group induced the secretion of more extracellular matrix and improved the chondrogenic differentiation potential of stem cells. Finally, thus hydrogel promoted the tissue repair of cartilage defects. Conclusion: Modified hydrogel is effective in cartilage tissue repair.

Despite advanced implant sterilization and aseptic surgical techniques, implant-associated infection remains a major challenge for orthopedic surgeries. The subject of bacterial biofilms is receiving increasing attention, probably as a result of the wide acknowledgement of the ubiquity of biofilms in the clinical environment, as well as the extreme difficulty in eradicating them. Biofilm can be defined as a structured microbial community of cells that are attached to a substratum and embedded in a matrix of extracellular polymeric substances (EPS) that they have produced. Biofilm development has been proposed as occurring in a multi-step process: (i) attachment and adherence, (ii) accumulation/maturation due to cellular aggregation and EPS production, and (iii) biofilm detachment (also called dispersal) of bacterial cells. In all these stages, characteristic proteinaceous and non-proteinaceous compounds are expressed, and their expression is strictly controlled. Bacterial biofilm formation around implants shelters the bacteria and encourages the persistence of infection, which could lead to implant failure and osteomyelitis. These complications need to be treated by major revision surgeries and extended antibiotic therapies, which could lead to high treatment costs and even increase mortality. Effective preventive and therapeutic measures to reduce risks for implant-associated infections are thus in urgent need.

Hydrogen has been used to suppress tumor growth with considerable efficacy. Inhalation of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen administration. We have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based biomaterials. However, the underlying mechanism of hydrogen's role in cancer treatment remains ambiguous. Here, we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based biomaterials. We find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins, as demonstrated by the in vitro RNA sequencing and protein expression analysis. Then, the P53 proteins disrupt the membrane potential of mitochondria, activate autophagy, suppress the reactive oxygen species in cancer cells, and finally result in tumor suppression. The anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a mouse. We also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2 μL/mm³ per day, which is much lower than that required for hydrogen inhalation. Taken together, these findings reveal the release of H₂ from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway, which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.

Background: Osteomyelitis causes marked disability and is one of the most challenging diseases for orthopaedists to treat because of the considerable rate of infection recurrence. In this study, we proposed and assessed the debridement-reconstruction-docking (DRD) system for the treatment of lower-extremity osteomyelitis. This procedure comprises 3 surgical stages and 2 preoperative assessments; namely, pre-debridement assessment, debridement, pre-reconstruction assessment, reconstruction, and docking-site management. We evaluated the use of the DRD system compared with the Ilizarov technique, which is defined as a 1-stage debridement, osteotomy, and bone transport. Methods: This retrospective cohort included 289 patients who underwent either DRD or the Ilizarov technique for the treatment of lower-extremity osteomyelitis at a single institution between January 2013 and February 2021 and who met the eligibility criteria. The primary outcome was the rate of infection recurrence. Secondary outcomes included the external fixator index (EFI), refracture rate, and the Paley classification for osseous and functional results. An inverse-probability-weighted regression adjustment model was utilized to estimate the effect of the DRD system and Ilizarov technique on the treatment of lower-extremity osteomyelitis. Results: A total of 131 and 158 patients underwent DRD or the Ilizarov technique, respectively. The inverse-probability-weighted regression adjustment model suggested that DRD was associated with a significant reduction in infection recurrence (risk ratio [RR], 0.26; 95% confidence interval [CI], 0.13 to 0.50; p < 0.001) and EFI (−6.9 days/cm, 95% CI; −8.3 to −5.5; p < 0.001). Patients in the DRD group had better Paley functional results than those in the Ilizarov group (ridit score, 0.55 versus 0.45; p < 0.001). There was no significant difference between the 2 groups in the rate of refracture (RR, 0.87; 95% CI, 0.42 to 1.79; p = 0.71) and Paley osseous results (ridit score, 0.51 versus 0.49; p = 0.39). Conclusions: In this balanced retrospective cohort of patients with lower-extremity osteomyelitis, the use of the DRD system was associated with a reduced rate of infection recurrence, a lower EFI, and better Paley functional results compared with the use of the Ilizarov technique. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Although concerns over the environmental impact of excess P in the excreta from pig production and governmental regulations have driven research toward reducing dietary supplementation of P to swine diets for over a decade, recent dramatic increases in feed costs have further motivated researchers to identify means to further reduce dietary P supplementation. We have demonstrated that genetic background impacts P utilization in young pigs and have identified genetic polymorphisms in several target genes related to mineral utilization. In this study, we examined the impact of a SNP in the calcitonin receptor gene (CALCR) on P utilization in growing pigs. In Exp. 1, 36 gilts representing the 3 genotypes identified by this CALCR SNP (11, 12, and 22) were fed a P-adequate (PA) or a marginally P-deficient (approximately 20% less available P; PD) diet for 14 wk. As expected, P deficiency reduced plasma P concentration, bone strength, and mineral content (P < 0.05). However, the dietary P deficiency was mild enough to not affect the growth performance of these pigs. A genotype × dietary P interaction (P < 0.05) was observed in measures of bone integrity and mineral content, with the greatest reduction in bone strength and mineral content due to dietary P deficiency being associated with the allele 1. In Exp. 2, 168 pigs from a control line and low residual feed intake (RFI) line were genotyped for the CALCR SNP and fed a PA diet. As expected, pigs from the low RFI line consumed less feed but also gained less BW when compared with the control line (P < 0.05). Although ADFI did not differ between genotypes, pigs having the 11 genotype gained less BW (P < 0.05) than pigs having the 12 or 22 genotypes. Pigs of the 11 and 12 genotypes had bones that tolerated greater load when compared with animals having the 22 genotype (P < 0.05). A similar trend was observed in bone modulus and ash % (P < 0.10). These data are supportive of the association of this CALCR SNP with bone integrity and its response to dietary P restriction. Although the allele 1 is associated with greater bone integrity and mineral content during adequate P nutrition, it is also associated with the greatest loss in bone integrity and mineral content in response to dietary P restriction. Understanding the underlying genetic mechanisms that regulate P utilization may lead to novel strategies to produce more environmentally friendly pigs.