The aim of this article is to study how andrographolide-releasing collagen scaffolds influence rabbit articular chondrocytes in maintaining their specific phenotype under inflammatory environment. Physical blending combined with vacuum freeze-drying method was utilized to prepare the andrographolide-releasing collagen scaffold. The characteristics of scaffold including its surface morphology and porosity were detected with environmental scanning electron microscope (ESEM) and a density instrument. Then, the release of andrographolide from prepared scaffolds was measured by UV-visible spectroscopy. Rabbit chondrocytes were isolated and cultured in vitro and seeded on andrographolide-releasing collagen scaffolds. Following culture with normal medium for 3 d, seeded chondrocytes were cultured with medium containing interleukin-1 beta (IL-1β) to stimulate inflammation in vitro for 7 d. The proliferation, morphology and gene transcription of tested chondrocytes were detected with Alamar Blue assay, fluorescein diacetate (FDA) staining and reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) test respectively. The results showed that the collagen scaffolds prepared by vacuum freeze-dry possess a high porosity close to 96%, and well-interconnected chambers around (120.7±17.8) μm. The andrographolide-releasing collagen scaffold continuously released andrographolide to the PBS solution within 15 d, and collagen scaffolds containing 2.22% andrographolide significantly inhibit the proliferation of chondrocytes. Compared with collagen scaffolds, 0.44% andrographolide-containing collagen scaffolds facilitate chondrocytes to keep specific normal morphologies following 7 d IL-1β induction. The results obtained by RT-qPCR confirmed this effect by enhancing the transcription of tissue inhibitor of metalloproteinase-1 (TIMP-1), collagen II (COL II), aggrecan (Aggrecan) and the ratio of COL II/ collagen I(COL I), meanwhile, reversing the promoted transcription of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13). In conclusion, our research reveals that andrographolide-releasing (0.44%) collagen scaffolds enhance the ability of chondrocytes to maintain their specific morphologies by up-regulating the transcription of genes like COL II, Aggrecan and TIMP-1, while down-regulating the transcription of genes like MMP-1 and MMP-13 which are bad for phenotypic maintenance under IL-1β simulated inflammatory environment. These results implied the potential use of andrographolide-releasing collagen scaffold in osteoarthritic cartilage repair.
Objective To explore the clinical application value of mineralized collagen (MC) bone scaffolds in repairing various types of skull defects, and to assess the suitability and repair effectiveness of porous MC (pMC) scaffolds, compact MC (cMC) scaffolds, and biphasic MC composite (bMC) scaffolds. Methods A retrospective analysis was conducted on the clinical data of 105 patients who underwent skull defect repair with pMC, cMC, or bMC between October 2014 and April 2022. The cohort included 63 males and 42 females, ranging in age from 3 months to 55 years, with a median age of 22.7 years. Causes of defects included craniectomy after traumatic surgery in 37 cases, craniotomy in 58 cases, tumor recurrence or intracranial hemorrhage surgery in 10 cases. Appropriate MC scaffolds were selected based on the patient’s skull defect size and age: 58 patients with defects <3 cm² underwent skull repair with pMC (pMC group), 45 patients with defects ≥3 cm² and aged ≥5 years underwent skull repair with cMC (cMC group), and 2 patients with defects ≥3 cm² and aged <5 years underwent skull repair with bMC (bMC group). Postoperative clinical follow-up and imaging examinations were conducted to evaluate bone regeneration, the biocompatibility of the repair materials, and the occurrence of complications. Results All 105 patients were followed up 3-24 months, with an average of 13 months. No material-related complication occurred in any patient, including skin and subcutaneous tissue infection, excessive ossification, and rejection. CT scans at 6 months postoperatively showed bone growth in all patients, and CT scans at 12 months postoperatively showed complete or near-complete resolution of bone defects in all patients, with 58 cases repaired in the pMC group. The CT values of the defect site and the contralateral normal skull bone in the pMC group at 12 months postoperatively were (1 123.74±93.64) HU and (1 128.14±92.57) HU, respectively, with no significant difference (t=0.261, P=0.795). Conclusion MC exhibits good biocompatibility and osteogenic induction ability in skull defect repair. pMC is suitable for repairing small defects, cMC is suitable for repairing large defects, and bMC is suitable for repairing pediatric skull defects.