## 2 Material and Methods
### Animal Model  
Ten male New Zealand White rabbits were supplied by a qualified laboratory animal supply center (La Granja cunicola San Bernardo, S.L., Tulebras, Navarra), and were quarantined for 3 weeks prior to commencement of the study. They were aged between 18 and 21 weeks and weighed between 3.7 and 4.0 kg. The animals were housed in individual enriched cages in the Animal Experimentation Service Facility of the University of Santiago de Compostela (Lugo, Spain) following ethical approval (procedure code: 03/18/LU-002) as a randomized controlled trial with one inter-subject control. Conditions such as temperature (15-21 \({}^{\circ}\)C), humidity, air renewal, and cycle time (12 h alternating cycles of light and dark) were controlled according to Annex II of Directive 86/609/EEC. The animals were fed with dry feed prepared in the form of pellets, sterilized and specially manufactured for the feeding of laboratory animals. The center's head of animal welfare, along with staff and the researchers, watched over the health of the animals throughout the experiment. There were no unexpected deaths. After a quarantine, animals were premedicated with ketamine 25 mg/kg/IM (Ketamidor(r) 100 mg/mL; Richter pharma AG, Wels, Austria), medetomidine 50 mg/kg/IM (Sedededorm(r) 1 mg/mL; Vetpharma Animal Health SL, Barcelona, Spain), and buprenorphine 0.03 mg/kg (Bupaq(r) 0.3 mg/mL; Richter pharma AG). The anesthesia was maintained by the inhalation of an O\({}_{2}\) and 2% isoflurane (Vetffurane; Virbac SA, Caro, France) mixture using a facemask. After aseptic preparation of the skin, a lateral approach of the distal femur was performed, affecting the skin and subcutaneous tissue to subsequently dissect the musculature and expose the surface of the lateral femoral conudyle with a periosteal elevator. A 6 mm defect was created using a trephine connected to a surgical motor INTRAsurg(r) 300 (KaVo, Biberach, Germany). Once the biomaterial was placed, in the lateromedial direction, the wound was sutured using 4-0 vicryl in deep planes and 3-0 nylon for the skin. The control biomaterial was placed in the contralateral limb following the same procedure. The 2 types of biomaterial were randomly assigned a total of 5 times to both the left and right sides based on a computer-generated randomization list. After wound closure, the skin was soaked with povidence solution. After the surgical intervention, atipamezole (0.15 mg/kg/IM; Nosedorm(r) 5 mg/mL; Vetpharma Animal Health SL) was administered to reverse the effects of the medetomidine. The animals were monitored and returned to their accommodation, where they remained throughout the experimental period. After the surgeries, pain was controlled with buprenorphine (0.01-0.03 mg/kg/IM, Bupaq(r) 0.3 mg/mL; Richter pharma AG) for 3 days and with meloxicam (0.2 mg/kg/SC, Metacam, Boehringer) for 5 days. As a prophylactic antibiotic, we used enrofloxacin(5 mg/kg/12 h, Syvaquinol(r) 10% Oral Solution; Syva labs) for 3 weeks. In addition, the condition of the wounds was evaluated twice a week, and the cages were cleaned each time. A bone graft was placed in each distal femur of all animals. In other words, a total of 20 bone grafts were placed in the 10 animals--2 different bone grafts per animal. To avoid errors due to the implantation side, 5 bone grafts of each type (test or control) were placed in the left femurs, and 5 of each type in the right femurs. The trial period used was 12 weeks. The animals were sacrificed with an overdose of intravenous sodium pentobarbital (Dolethal 200 mg/mL, Vetoquinol) after sedation with ketamine 25 mg/kg + medetomidine 50 ug/kg + buprenorphine 0.03 mg/kg. Subsequently, the distal femurs were recovered by dissection and the use of a bone saw. Specimens were immediately immersed in a 10% buffered formalin solution for a minimum of 2 weeks until the time of processing. For identification, we used a code consisting of a number and a letter. The number indicated the animal (from 1 to 10) and the letter the side of the femur (right-R and left-L).