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<p>Collagen-based fillers are increasingly recognized as versatile biomaterials for soft-tissue augmentation, yet evidence guiding the enzymatic management of collagen-associated complications remains limited. Here, we performed a systematic characterization of two National Medical Products Administration-approved porcine type I collagen fillers (PCFs), glutaraldehyde cross-linked PCF (CL-PCF) and uncross-linked PCF (UCL-PCF), using hyaluronic acid (HA) filler as a clinical benchmark. CL-PCF exhibited superior mechanical robustness and markedly enhanced resistance to collagenase degradation relative to UCL-PCF. In a rabbit ear embolization model, both PCFs induced significantly milder vascular ischemic manifestations than HA. In vivo enzymolysis assessment in SD rats demonstrated that collagenase concentrations ≤ 300 IU/mL effectively facilitated the controlled degradation of PCFs without inducing notable tissue injury, whereas higher concentrations resulted in extensive matrix loss, hemorrhage, and focal skeletal muscle lysis with inflammatory infiltration. This study provides the first integrated mechanistic and safety-oriented framework for understanding the enzymolysis of collagen fillers and optimizing collagenase-based interventions. These findings offer clinical guidance for complication management and inform evidence-based decision-making in collagen filler applications.</p> Graphical Abstract <p></p>

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Enzymolysis behavior and safe collagenase management of porcine collagen fillers

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Hang Wang,
  • Rui Zhao,
  • Chihchieh Lo,
  • Donglei Yu,
  • Hsien-Li Peter Peng,
  • Jing Wang,
  • He Qiu

摘要

Collagen-based fillers are increasingly recognized as versatile biomaterials for soft-tissue augmentation, yet evidence guiding the enzymatic management of collagen-associated complications remains limited. Here, we performed a systematic characterization of two National Medical Products Administration-approved porcine type I collagen fillers (PCFs), glutaraldehyde cross-linked PCF (CL-PCF) and uncross-linked PCF (UCL-PCF), using hyaluronic acid (HA) filler as a clinical benchmark. CL-PCF exhibited superior mechanical robustness and markedly enhanced resistance to collagenase degradation relative to UCL-PCF. In a rabbit ear embolization model, both PCFs induced significantly milder vascular ischemic manifestations than HA. In vivo enzymolysis assessment in SD rats demonstrated that collagenase concentrations ≤ 300 IU/mL effectively facilitated the controlled degradation of PCFs without inducing notable tissue injury, whereas higher concentrations resulted in extensive matrix loss, hemorrhage, and focal skeletal muscle lysis with inflammatory infiltration. This study provides the first integrated mechanistic and safety-oriented framework for understanding the enzymolysis of collagen fillers and optimizing collagenase-based interventions. These findings offer clinical guidance for complication management and inform evidence-based decision-making in collagen filler applications.

Graphical Abstract