Modeling Principle

The Pig Burn Injury Model is a SCI gold-standard large-animal pathological model of skin burn injury established by constant-temperature and constant-pressure standardized hot water/heat source contact scalding. It accurately recapitulates the complete pathological cascade of clinical thermal injury, including full-thickness or deep dermal skin destruction, local tissue coagulative necrosis, wound inflammatory cascade activation, systemic oxidative stress disorder, increased vascular permeability, wound exudation and edema, granulation tissue hyperplasia and remodeling, and scar repair, and compensates for the experimental defects of rodent small animals with huge differences from humans in skin thickness, dermal structure, pilosebaceous distribution, skin hemodynamics and wound healing rhythm.

The epidermal layered structure, dermal collagen arrangement, skin appendage distribution, wound inflammatory immune response, epidermal stem cell proliferation and differentiation rule, and skin microcirculation remodeling mechanism of Bama minipig skin are highly homologous to human skin. The temporal changes of immediate wound coagulative necrosis, acute exudative swelling, inflammatory cell infiltration, subacute granulation tissue growth and chronic epithelial crawling scar remodeling after standardized controllable thermal scalding are fully consistent with the disease progression of clinical second-degree and deep second-degree thermal burns. A constant-temperature heat source acts precisely on local skin to cause dermal collagen denaturation and coagulation and irreversible cell necrosis, immediately activating the systemic trauma stress system. Local injury activates skin innate immune cells and massively releases pro-inflammatory factors such as TNF-α, IL-1β, IL-6 and IL-8, triggering local inflammatory infiltration and systemic inflammatory response syndrome. Meanwhile, massive accumulation of ROS and exhaustion of the antioxidant system lead to oxidative stress imbalance, which further aggravates wound tissue damage, vasodilation exudation and tissue edema. The wound repair program is activated in the late injury stage; inflammatory cells clear necrotic tissues, and fibroblast proliferation, collagen deposition and neovascularization gradually complete granulation tissue remodeling and epithelial healing, which fully recapitulates the classic pathogenesis and repair cascade of human thermal burns: thermal tissue necrosis-localized inflammatory burst-systemic stress disorder-granulation hyperplasia remodeling-wound scar repair.

Minipigs have uniform skin thickness, flat body surface, no natural skin fold lesions and uniform heat source contact force. The size, depth and injury gradient of burn wounds are highly controllable with minimal intra-group individual differences and excellent modeling reproducibility. It can clearly distinguish three-stage phenotypes of burn injury: acute inflammatory stage, proliferative repair stage and scar remodeling stage, serving as a standardized large-animal gold-standard model for preclinical translational research on burn pathogenesis, wound anti-inflammation and anti-oxidation, wound healing promotion, scar hyperplasia inhibition, burn dressing and repair materials, and burn systemic complication prevention and treatment.

Modeling Success Criteria

Macroscopic Wound Phenotype and Healing Characteristics

The dorsal skin of the blank control group was complete and smooth with uniform color, no swelling and exudation and intact epidermal structure. The model group showed immediate wound whitening and coagulative necrosis after modeling, with obvious wound swelling, exudation and scab formation within 24 h. On Day 7 after modeling, the wound necrotic layer was clear with the most severe inflammatory exudation and no spontaneous epithelial repair. On Day 14, bright red granulation tissue proliferated with wound contraction and gradual scab shedding. On Day 21, the wound was not completely epithelialized with obvious scar hyperplasia and skin contracture, showing extremely significant differences in skin structure, appearance and healing status from the blank group, confirming preliminary successful construction of the deep second-degree burn model.

Quantitative Biochemical Gold-Standard Indexes of Serum and Wound Tissue

The expression of pro-inflammatory factors TNF-α, IL-1β, IL-6 and IL-8 in serum and wound tissues of the model group was extremely significantly upregulated compared with the blank group; the oxidative stress index MDA content increased significantly while the antioxidant activity of SOD decreased sharply, presenting typical post-burn oxidative stress imbalance; the wound repair factors VEGF and TGF-β showed temporally abnormal expression with excessive early inflammatory activation and abnormal late collagen deposition, fully matching the core biochemical diagnostic characteristics of clinical deep second-degree burns: acute inflammatory burst, oxidative stress disorder, abnormal granulation proliferation and scar remodeling imbalance.

Skin Histopathological Characteristics

Combined HE, Masson, Sirius red and CD31 staining of skin tissues showed characteristic temporal pathological injury and repair changes of deep second-degree burns:

1. Acute stage on Day 7 after modeling: full-thickness epidermal coagulative necrosis and shedding, superficial dermal collagen degeneration and coagulation, diffuse infiltration of a large number of inflammatory cells and obvious tissue edema with no neovascularization and granulation tissue;

2. Middle repair stage on Day 14 after modeling: residual skin appendages in deep dermis, massive fibroblast proliferation, dense neovascularization, thickened granulation tissue, disordered collagen fiber deposition and reduced inflammatory cell infiltration;

3. Terminal remodeling stage on Day 21 after modeling: partial wound coverage by epithelial crawling, thick and disorderly arranged collagen fibers, massive scar tissue formation and destroyed and missing skin appendage structures, which perfectly recapitulates the pathological grading characteristics of injury and repair of human deep second-degree burns.

Core Inflammatory, Oxidative Stress and Repair Pathway Indexes

The NF-κB inflammatory pathway of the model group was persistently activated in the acute stage, driving cascade release of downstream inflammatory factors; the systemic oxidative stress pathway was overactivated with inhibited antioxidant system, forming post-burn oxidative damage; the wound TGF-β/Smad collagen remodeling pathway was abnormally activated with disordered temporal sequence of VEGF-mediated neovascularization, which accurately conforms to the complete pathogenic and repair mechanism of thermal burns: thermal tissue necrosis-inflammatory and oxidative damage-granulation proliferation disorder-abnormal scar remodeling, serving as the core academic criterion for confirming successful modeling.

Model Advantages

This model is a well-recognized exclusive large-animal gold-standard model for thermally induced deep second-degree skin injury in burn SCI field. Standardized constant-temperature and constant-pressure scalding can accurately, stably and repeatably construct deep second-degree burn injury and repair phenotypes highly homologous to humans. The skin structure, collagen metabolism, wound inflammatory response, neovascularization and scar remodeling mechanism of minipig skin are almost consistent with human skin, completely solving the experimental defects of rodents such as thin skin, excessive healing speed and no scar hyperplasia. The modeling adopts pure thermal injury without surgical trauma and drug toxin interference, which accurately simulates the complete clinical course of accidental burns, wound inflammatory exudation, granulation proliferation and scar formation. The wound size and depth are controllable with uniform injury gradient among groups, extremely low data dispersion and excellent reproducibility. It is suitable for preclinical large-animal pharmacodynamic evaluation of burn anti-inflammatory and antioxidant drugs, wound repair dressings, healing-promoting biomaterials and anti-scar preparations. With sufficient samples and comprehensive detection dimensions, it has high clinical transformation credibility and high recognition in high-score SCI journals of burns, wound repair and dermatology, suitable for National Natural Science Foundation, master/doctor project opening, graduation thesis of burn surgery/dermatology and translational medical research of skin trauma regeneration.

Research Applications

The Pig Burn Injury Model is corely applied to basic research on thermal injury-induced acute skin inflammatory burst, oxidative stress imbalance, dermal collagen degeneration and necrosis, abnormal fibroblast proliferation, neovascularization disorder and abnormal scar remodeling. It is specially used for screening and evaluating burn repair small-molecule drugs, natural active extracts, medical wound dressings, skin repair biomaterials and anti-scar targeted preparations with effects of inhibiting burn wound inflammatory exudation, scavenging oxygen free radicals, reducing oxidative damage, promoting granulation tissue growth, accelerating epithelial healing, inhibiting abnormal collagen deposition and improving scar hyperplasia. It is widely adopted for excavation of burn wound injury and repair targets, elucidation of skin inflammatory and oxidative regulatory networks, and large-animal preclinical in-vivo pharmacodynamic verification of burn repair drugs and dressings, serving as a scarce and essential standardized large-animal gold-standard model in the fields of burn surgery, dermatology and trauma repair and regenerative medicine.

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