Theophylact of Ohrid

But the Lord answers: It will be of no benefit to My Mother to be My Mother if She does not possess all the virtues within Herself. Likewise, kinship will be of no benefit to My brothers. For only those are true relatives of Christ who do the will of God. So in saying this, He does not disown His Mother, but shows that She will be worthy of honor not merely for giving birth alone, but also for every other good deed: for if She did not have this, others would have seized the honor of kinship before Her.

Commentary on Mark ↗

Gregory the Dialogist

For Jesus, our Creator and Redeemer, pretends not to know His mother, and indicates who is His mother and who are His relatives not through kinship of the flesh, but through union of the spirit, saying: "Who is my mother, and who are my brethren? …

Forty Gospel Homilies, Homily 3 ↗

Bede

Being asked therefore by a message to go out, He declines, not as though He refused the dutiful service of His mother, but to show that He owes more to His Father's mysteries than to His mother's feelings. Nor does He rudely despise His brothers, but, preferring His spiritual work to fleshly relationship, He teaches us that religion is the bond of the heart rather than that of the body. …

Catena Aurea by Aquinas ↗