This experimental study (domestic pig) examined the bone formation after filling defined defects of the frontal skull with autogenous bone or a deproteinized bovine bone matrix (DBBM) in combination with platelet-rich plasma (PRP). Six groups, both materials with and without PRP in two different concentrations (4.1x and 6.5x referring to untreated whole blood) were evaluated at 2, 4, 12, and 26 weeks by means of immunohistochemical staining for different bone matrix proteins, microradiography, light microscopy and polychromatic fluorescence labeling. The sequential expression of bone matrix proteins reflected the specific roles these proteins fulfil in the mineralization of hard tissue. Collagen I expression at 2 weeks was enhanced in all autogenous bone groups. No specific modification of the collagen I expression was found after use of DBBM with or without PRP. Osteopontin and especially osteonectin showed a remarkable enhancement at 4 weeks in nearly all autogenous bone and DBBM groups. These increased levels closely resembled the mineralization content evaluated by microradiography at that time. For the three autogenous bone groups, an expression peak for osteocalcin was demonstrated at 12 weeks, further reflecting the way of de novo bone formation. The microradiographic evaluation demonstrated a statistically significant enhancement in bone regeneration by PRP only after use of autogenous bone plus PRP at 2 weeks (P = 0.002). After 4 weeks, mineralization values after use of autogenous bone were significantly lower if PRP was added to the autogenous bone (P = 0.002). No long-term effects of the PRP administration were found in the mineralization process. In all DBBM groups, bone formation remained unchanged, confirming the lack of any osteoinductive capacity of PRP. PRP modulated the expression of bone matrix proteins in this experimental setting. However, an enhancement of bone formation was demonstrated only at 2 weeks after application of the higher PRP concentration in combination with autogenous bone. In conjunction with an anorganic bovine bone no effects of PRP on defect mineralization were discovered, demonstrating the lack of osteoinductive capacity in PRP as well as in DBBM.