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Objective <p>To develop an isoniazid-loaded biomimetic mineralized collagen scaffold and assess its biocompatibility, osteogenic capacity, and anti-tuberculosis activity.</p> Methods <p>We fabricated a drug-loaded mineralized collagen scaffold from type I collagen using biomimetic mineralization self-assembly with isoniazid incorporated through molecular coprecipitation. Biocompatibility was assessed by subcutaneously implanting scaffolds in mice and quantifying IL-6 and TNF-α in surrounding tissues via enzyme-linked immunosorbent assay (ELISA). Twenty four SD rats were used to establish a critical bone defect model and divided into three groups: experimental group (drug loaded stent group), control group (no drug loaded stent group), and blank group (no stent implantation group). Eight rats were randomly selected from each group, and after a period of time, bone formation was detected by techniques such as HE staining, and immunohistochemistry. Anti-tuberculosis activity was determined by co-culturing sterilized scaffolds with Mycobacterium tuberculosis and evaluating bacterial growth through acid-fast staining, auramine-O staining, BACTEC MGIT 960 detection, and flow cytometry.</p> Results <p>Scaffold fabrication was successful. In mice, drug-loaded scaffolds produced significantly lower IL-6 and TNF-α levels than both controls at weeks 1 and 2, with no differences between blank and non-drug-loaded groups. By week 4, all groups showed reduced cytokine levels compared to week 1, most markedly in the drug-loaded group. In rats, histological analysis at weeks 6 and 12 revealed extensive soft tissue proliferation and neovascularization at defect sites, both significantly greater in the experimental group. Masson's trichrome staining demonstrated active osteogenesis in experimental animals at both time points. Immunohistochemistry showed markedly elevated OCN and BMP-2 expression in scaffold-treated defects versus minimal expression in controls. ImageJ quantification confirmed significantly higher expression of both proteins in the experimental group (<i>P</i> &lt; 0.05). At week 8, acid-fast and auramine-O staining showed complete suppression of Mycobacterium<i>.</i> tuberculosis growth with drug-loaded scaffolds, while both controls exhibited substantial bacterial growth. Flow cytometry confirmed significantly lower viable bacterial counts and fluorescence intensity with drug-loaded scaffolds compared to controls, with no differences between control groups.</p> Conclusion <p>This isoniazid-loaded biomimetic mineralized collagen scaffold demonstrates potent anti-inflammatory and anti-tuberculosis effects alongside robust osteogenic capacity, offering a promising treatment strategy for bone defects resulting from osteoarticular tuberculosis.</p>

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Anti-tuberculosis and osteogenic properties of an isoniazid-loaded biomimetic mineralized collagen scaffold

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Xu Fang,
  • Qian Wang,
  • ZhiLiang Yu,
  • Han Li,
  • Aihua Feng,
  • JunFeng Dong

摘要

Objective

To develop an isoniazid-loaded biomimetic mineralized collagen scaffold and assess its biocompatibility, osteogenic capacity, and anti-tuberculosis activity.

Methods

We fabricated a drug-loaded mineralized collagen scaffold from type I collagen using biomimetic mineralization self-assembly with isoniazid incorporated through molecular coprecipitation. Biocompatibility was assessed by subcutaneously implanting scaffolds in mice and quantifying IL-6 and TNF-α in surrounding tissues via enzyme-linked immunosorbent assay (ELISA). Twenty four SD rats were used to establish a critical bone defect model and divided into three groups: experimental group (drug loaded stent group), control group (no drug loaded stent group), and blank group (no stent implantation group). Eight rats were randomly selected from each group, and after a period of time, bone formation was detected by techniques such as HE staining, and immunohistochemistry. Anti-tuberculosis activity was determined by co-culturing sterilized scaffolds with Mycobacterium tuberculosis and evaluating bacterial growth through acid-fast staining, auramine-O staining, BACTEC MGIT 960 detection, and flow cytometry.

Results

Scaffold fabrication was successful. In mice, drug-loaded scaffolds produced significantly lower IL-6 and TNF-α levels than both controls at weeks 1 and 2, with no differences between blank and non-drug-loaded groups. By week 4, all groups showed reduced cytokine levels compared to week 1, most markedly in the drug-loaded group. In rats, histological analysis at weeks 6 and 12 revealed extensive soft tissue proliferation and neovascularization at defect sites, both significantly greater in the experimental group. Masson's trichrome staining demonstrated active osteogenesis in experimental animals at both time points. Immunohistochemistry showed markedly elevated OCN and BMP-2 expression in scaffold-treated defects versus minimal expression in controls. ImageJ quantification confirmed significantly higher expression of both proteins in the experimental group (P < 0.05). At week 8, acid-fast and auramine-O staining showed complete suppression of Mycobacterium. tuberculosis growth with drug-loaded scaffolds, while both controls exhibited substantial bacterial growth. Flow cytometry confirmed significantly lower viable bacterial counts and fluorescence intensity with drug-loaded scaffolds compared to controls, with no differences between control groups.

Conclusion

This isoniazid-loaded biomimetic mineralized collagen scaffold demonstrates potent anti-inflammatory and anti-tuberculosis effects alongside robust osteogenic capacity, offering a promising treatment strategy for bone defects resulting from osteoarticular tuberculosis.