The Serbian was withdrawn after 12 minutes of a 1-1 draw with Genoa with medical tests confirming three tears in his left ankle as a result of a challenge from Matuzalem.
The 22-year-old was allowed a week of rest before further tests determined conservative treatment would be more successful than invasive surgery.
A statement published on sampdoria.it read: "Orthopaedic consultant professor Claudio Mazzola and club doctor Amedeo Baldari have ruled out invasive surgery for Nenad Krsticic.
"Following the ankle injury he suffered in the derby on April 14, we will proceed with a conservative treatment."
Krsticic moved to Liguria from OFK Beograd in 2008 and had made 25 league appearances for Samp this season, scoring one goal in a 2-2 draw at Fiorentina.
He was diagnosed with Burkitt's lymphoma, a form of blood cancer, in December 2008 but made a full recovery to establish himself as Sampdoria's playmaker alongside Pedro Mba Obiang.
He then played his part as the Blucerchiati reached the top flight through the Serie B play-offs last season before earning his first cap for Serbia in February during a friendly match against Cyprus.