Bone healing after amputation of mouse digits and newt limbs: implications for induced regeneration in mammals.

Postamputational healing was compared in nonregenerating and regenerating animals to determine whether bone healing might interfere with a regenerative response in mice. More than 150 mouse toes and 100 newt limbs were examined at the light microscope level. Stages of normal bone healing with approximate times of occurrence were established. Major differences in healing of these two species were seen. The periosteum produced hyaline cartilage, woven bone, and chondroid bone in mice, but only hyaline cartilage in newts. The endosteum produced woven bone in mice but no new growth in newts. Dead bone persisted in mice but was removed in newts. The marrow cavity became sealed in mice but remained open in newts. Despite these differences both animals produced skeletal tissue distal to the amputation plane. Woven bone formed distal to the amputation plane of mice. Cartilage formed distal to the amputation plane of newts, but cartilage was never seen distal to the plane of mice. Results of previous studies reveal that cartilage can be formed distal to the amputation plane of experimentally treated mice. Thus, although it does not regenerate, mouse bone is capable of producing, distal to the amputation plane, the type of skeletal tissue which appears at that location during an epimorphic regenerative response. This observation, in combination with other experimental results, indicates that both skeletal and soft tissues at the amputation site of treated mammals can resemble comparable tissues of newt limbs at an early stage of regeneration.