Objectives— To report an ovine model that can be used to evaluate the efficacy of bone substitutes for repair of segmental diaphyseal bone defects.

Study Design— Experimental study.

Animals— Eleven 2‐year‐old Pré‐Alpes Sheep.

Methods— Mid‐diaphyseal metatarsal bone defects (25 mm long) were stabilized by a dynamic compression plate over a polymethylmethacrylate (PMMA) cement spacer, and by external coaptation. The PMMA spacer was removed at 6 weeks by incising the encapsulating membrane. The defect remained unfilled (Group 1; n=5) or was filled with morselized autologous corticocancellous graft (Group 2; n=6), the membrane sutured closed, and external coaptation applied for 6 months, when healing was evaluated.

Results— Radiographic, computed tomographic, and histologic examinations at 6 months after the 2nd surgery revealed non‐union in ungrafted defects whereas grafted defects showed bone healing. The induced membrane had blood vessels, CBFA1+ cells, and very few macrophages entrapped in a collagenous tissue positive for type I collagen.

Conclusion— This ovine metatarsal defect model resulted in a critical‐size defect (non‐union) that healed when grafted. The PMMA‐induced membrane constrained the graft, was well vascularized, and may have osteogenic properties.

Clinical Relevance— This model may be useful to evaluate new strategies in bone tissue engineering because the PMMA‐induced membrane may help confine bone morphogenetic proteins, skeletal stem cells, or other agents to the defect cavity where they could be useful to enhance bone formation.