Summary Statement. A porcine model using Yucatan minipigs was found to be very promising for the investigation of healing around transcutaneous osseointegrated implants. Pigs demonstrated surprising agility and adaptability including the ability to ambulate on three legs during the immediate postoperative period. Introduction. Previous non weight-bearing and weight-bearing caprine, canine and ovine models have evaluated design, material, and biological coating variations in an attempt to improve the wound healing and skin-implant seal around transcutaneous osseointegrated implants. Although these models have primarily been used as a window into the application of transcutaneous osseointegrated implants in humans, some important model characteristics affecting wound healing and infection have been missing including: 1) replication of the physiological tissue response, and 2) availability of a transcutaneous site with sufficient soft tissue coverage. Pig skin, like human, is relatively hairless, tightly attached to the subcutaneous tissue, vascularised by a cutaneous blood supply, and healed by means of epithelialization. Swine have been extensively utilised for superficial and deep wound healing studies and can offer ample soft tissue coverage following a lower limb amputation. Development of a porcine model is important for continued understanding and improvement of weight-bearing transcutaneous osseointegration. Methods. Two male Yucatan mini-pigs (9 months, 36kg) were fit with transcutaneous osseointegrated prostheses using a single-stage transtibial amputation and prosthesis implantation procedure. The endo-prosthesis consisted of a cylindrical intraosseous threaded section and a smooth transcutaneous section. The transcutaneous sections were smooth to promote epithelialization and deter direct skin-implant adhesion. The implants were custom manufactured from medical grade Ti-6Al-4V alloy. The exo-prosthesis, consisting of an adjustable length leg and foot, was attached by clamp to the supercutaneous portion of the implant following either one or two days of sling constraint to limit initial weight-bearing. Various exo-prosthesis designs and configurations were trialed. The animals’ behavior and gait were closely observed. Weight-bearing was monitored using a force plate. At 5 and 8 weeks, clinical, microbiological, and histological data were examined to assess wound healing and infection at the skin-bone-implant interface. Results. The pigs demonstrated surprising agility and adaptability. They were able to successfully ambulate on three legs during the post-op period before weight-bearing was permitted. They adapted quickly to changes in exo-prosthesis design, position, and length. Although bacterial colonization was verified, neither of the animals exhibited clinical signs of infection over the respective eight and five week studies. Histological results indicated that there was no skin to implant adhesion but that epithelial growth was progressing towards the implant in one animal. Healing of the transcutaneous wound site showed substantial progress but a definitive skin seal was non-existent at the eight week time point. Discussion/Conclusion. This is likely the first animal model developed, having soft tissue characteristics similar to those found in humans, in which an axially-loaded, weight-bearing implant was successfully used. Results indicated that this porcine model offers many advantages over previous models for the development, evaluation, and comparison of the various techniques being advocated to achieve successful transcutaneous osseointegration in humans. The Yucatan miniature pig's ability to ambulate on three legs during the immediate post-operative period and quickly adjust to changes in the exo-prosthesis design, coupled with their physiological similarity to humans, makes them a valuable model for future studies

Articular cartilage repair is assumed to improve by covering the cartilage lesion with a biomaterial scaffold tailored to the specific requirements of the weight-bearing joint surface. We have tested the feasibility of a novel composite collagen-polylactide scaffold rhCo-PLA in cartilage repair. To confirm these results and further challenge the scaffold, we tested it in a large porcine cartilage defect. A critical-sized full-thickness chondral defect was made in the medial femoral condyle of 18 domestic pigs. This technically widest possible defect size of 11×17 mm was determined in a pilot test. Five weeks later, the defect was either treated with the novel rhCo-PLA scaffold or left untreated to heal spontaneously. After four months, the medial condyles were evaluated macroscopically using Goebel's score, in which the worst possible result receives a total of 20 points and imaged with µCT to evaluate subchondral bone. Macroscopic score and subchondral bone microstructure were similar in both study groups. The total Goebel score was higher in spontaneous group (9.75±3.9 for spontaneous and 9.1±3.7 for rhCo-PLA, respectively) but differences between individual animals were large. Subchondral bone volume fraction was 48.2±3.6% for rhCo-PLA and 44.2±3.4% for spontaneous. Trabecular thickness was greater in operated joints (207.9±18.8 µm for spontaneous and 242.9±32.9 µm for rhCo-PLA) than in contralateral non-operated joints (193.3±15.1 µm and 213.4±33.2 µm, respectively). These preliminary data demonstrate that individual differences in the macroscopic appearance were large but there were no significant differences between the two study groups in the score or subchondral bone structure.

We hypothesised that meniscal tears treated with mesenchymal stem cells (MSCs) together with a conventional suturing technique would show improved healing compared with those treated by a conventional suturing technique alone. In a controlled laboratory study 28 adult pigs (56 knees) underwent meniscal procedures after the creation of a radial incision to represent a tear. Group 1 (n = 9) had a radial meniscal tear which was left untreated. In group 2 (n = 19) the incision was repaired with sutures and fibrin glue and in group 3, the experimental group (n = 28), treatment was by MSCs, suturing and fibrin glue.

At eight weeks, macroscopic examination of group 1 showed no healing in any specimens. In group 2 no healing was found in 12 specimens and incomplete healing in seven. The experimental group 3 had 21 specimens with complete healing, five with incomplete healing and two with no healing. Between the experimental group and each of the control groups this difference was significant (p < 0.001).

The histological and macroscopic findings showed that the repair of meniscal tears in the avascular zone was significantly improved with MSCs, but that the mechanical properties of the healed menisci remained reduced.

A pre-clinical experimental simulation model has been previously successfully developed, and was shown to have the potential for investigation of the biomechanical and tribological performance of early stage knee therapies. In order to investigate interventions that may necessitate sacrifice of the natural ligaments, it is necessary to replicate their function. This study investigated the most effective spring constraint conditions for the porcine knee model with the aim of replicating the natural ligament function. The replication of natural ligament function was achieved through the use of physical springs in the anterior-posterior (AP) axis. Spring-9 (9 N/mm) and spring-20 (20 N/mm) were set at different free lengths in a natural knee simulator. The A/P displacement and shear force outputs from porcine knee samples (N=6) were measured and the most appropriate spring setting was determined by comparing the outputs at different spring settings with intact knee. The A/P displacement of both spring-9 and spring-20 showed similar shapes to the all ligament control. Spring-9 with a free length of 4 mm and spring-20 with a free length of 5 mm showed minimal differences in A/P displacement output compared to the all ligament controls. There was no statistical difference between the two minimal differences either in A/P displacement or in shear force (paired t-test, p>0.05), which indicated that both conditions were appropriate spring constraint settings for the natural porcine knee model. A porcine knee simulation model with refined spring constraint conditions was successfully developed in this study. Human knee model is currently under investigation using the methodology developed in porcine knee model, which will be more appropriate to investigate the effect of early stage knee therapies on the tribological function of the natural knee

Introduction. Current treatments of rotational deformities of long bones in children are osteotomies and fixations. In recent years, the use of guided growth for correction of rotational deformities has been reported in several pre-clinical and clinical studies. Various techniques have been used, and different adverse effects, like growth retardation and articular deformities, have been reported. We tested a novel plate concept intended for correction of rotational deformities of long bones by guided growth, with sliding screw holes to allow for longitudinal growth, in a porcine model. Method. Twelve, 12-week-old female porcines were included in the study. Surgery was performed on the left femur. The right femur was used as control. Plates were placed distally to induce external rotation, as longitudinal growth occurred. CT-scans of the femurs were processed to 3-D models and used for measuring rotation. Result. The plates rotated as intended in all 12 porcines. One porcine was excluded due to congenital deformity of the proximal part of the femurs. Two porcines had cut-out of the proximal screw on the lateral side, observed at the end of the intervention. These two porcines were included in the results. We observed a Δrotation of 5.7° ± 2° in external direction (CI: 3.7°– 7.7°). ΔFemur length was -0.4 cm [-0.7 cm – 0 cm] equal to 1.5% shortening of the operated femur. No significant difference was observed in coronal or sagittal plane. Conclusion. Significant external rotation was achieved with minimal effect on longitudinal growth. While the use of guided growth for correction of rotational deformities is already being used clinically, it is still to be considered an experimental procedure with sparse evidence. This study shows promising results for the feasibility of the method in a large animal model and is an important first step in validating the technique and detecting possible adverse effects, before future clinical studies

The fixation of articular fractures, with many small osteochondral fragments, is a challenging unmet need where a bone adhesive would be a useful adjunct to standard treatments. Whilst there are no such adhesives in current clinical use, preclinical animal models have demonstrated good healing of bone in unloaded models using an adhesive based on phosphoserine modified calcium phosphate cement (PM-CPC). An ex-vivo human bone core model has shown that this adhesive bonds freshly harvested human bone. To confirm this adhesive is capable of supporting loaded osteochondral fragments a porcine model has been developed initially ex-vivo on the path to an in-vivo study. In this model bone cores, harvested from the medial knee condyle, are glued in place with the adhesive. In-vivo adjacent pairs of bone cores would be replaced with adhesive and a control with conventional pin fixation respectively. As osteochondral bone fragments have both bone and cartilage components, this suggested a dual adhesive strategy in which components designed for each tissue type are used. This concept has been explored in an ex-vivo porcine pilot study presented herewith. At the subchondral bone level, the PM-CPC was used. At the cartilage level, a second adhesive, a methacrylated phosphoserine containing hyaluronic acid (MePHa) hydrogel designed specifically for soft tissues was applied. This is a challenging model as both adhesives have to be used simultaneously in a wet field. The pilot showed that once the subchondral component is glued in place, the PM-CPC adhesive intruding into the cartilage gap can be removed before applying the cartilage adhesive. This enabled the MePHa adhesive to be injected between the cut cartilage edges and subsequently light-cured. This two-stage gluing method is demanding and an in-vivo pilot is necessary to perfect and prove the operative technique. Acknowledgements: The human bone core project was partially financed by Innovation Fund of Västra Götaland Region, Sweden. The MePHa hydrogel work was supported by a Swiss National Fund grant # CR23I3_159301

Introduction. Cartilage damage is a critical aspect of osteoarthritis progression, but effective imaging strategies remain limited. Consequently, multimodal imaging approaches are receiving increased attention. Gold nanomaterials, renowned for their therapeutic and imaging capabilities, hold promise in drug development. However, their potential for cartilage imaging is rarely discussed. Here, we developed a versatile nanomaterial, AuNC@BSA-Gd-I, for cartilage detection. By leveraging electrostatic interactions with sulfated glycosaminoglycans (sGAG), the AuNC@BSA-Gd-I can effectively penetrate damaged cartilage while accumulating minimally in healthy cartilage. This probe can be visualized or detected using CT, MRI, IVIS, and a gamma counter, providing a comprehensive approach to cartilage imaging. Additionally, we compared the imaging abilities, cartilage visualization capacities, and versatility of currently disclosed multimodal gold nanomaterials with those of AuNC@BSA-Gd-I. Method. The physicochemical properties of nanomaterials were measured. The potential for cartilage visualization of these nanomaterials was assessed using an in vitro porcine model. The sGAG content in cartilage was determined using the dimethylmethylene blue (DMMB) assay to establish the correlation between sGAG concentration and imaging intensity acquired at each modality. Results. The cartilage imaging abilities of AuNC@BSA-Gd-I for CT, MRI, and optical imaging were verified, with each imaging intensity demonstrating a strong correlation with the sGAG content (MRI; R2=0.93, CT; R2=0.83, IVIS; R2=0.79). Furthermore, AuNC@BSA-Gd-. 131. I effectively accumulated in defective cartilage tissue compared to healthy cartilage (23755.38 ± 5993.61 CPM/mg vs. 11699.97 ± 794.93 CPM/mg). Additionally, current gold nanomaterials excelled in individual imaging modalities but lacked effective multimodal imaging ability. Conclusion. Compared to current multimodal gold nanomaterials, AuNC@BSA-Gd-I demonstrates the potential to image cartilage across multiple medical instruments, providing investigators with a more powerful, visible, and convenient approach to detect cartilage defects. Acknowledgements. This work was financially supported by the National Health Research Institute, Taiwan (NHRI-EX112-11029SI), the National Science and Technology Council (NSTC 112-2314-B-182A-105-MY3), and Chang Gung Memorial Hospital, Taiwan (CMRPG8N0781 and CMRPG8M1281-3)

Introduction. Understanding knee joint biomechanics is crucial, but studying Anterior cruciate ligament (ACL) biomechanics in human adolescents is challenging due to limited availability cadaveric specimens. This study aims to validate the adolescent porcine stifle joint as a model for ACL studies by examining the ACL's behavior under axial and torsion loads and assessing its deformation rate, stiffness, and load-to-failure. Methods. Human knee load during high-intensity sports can reach 5-6 times body weight. Based on these benchmarks, the study applied a force equivalent to 5-times body weight of juvenile porcine samples (90 pounds), estimating a force of 520N. Experiments involved 30 fresh porcine stifle joints (Yorkshire breed, Avg 90 lbs, 2-4 months old) stored at -22°C, then thawed and prepared. Joints were divided into three groups: control (load-to-failure test), axially loaded, and 30-degree torsion loaded. Using a servo-hydraulic material testing machine, the tibia's longitudinal axis was aligned with the load sensor, and specimens underwent unidirectional tensile loading at 1 mm/sec until rupture. Data on load and displacement were captured at 100 Hz. Results. One-way ANOVA showed statistically significant differences in maximum failure force among loading conditions (p = 0.0039). Post hoc analysis indicated significant differences between the control and 500N (non-twisted) groups (p = 0.014) and between the control and 500N (twisted) groups (p = 0.003). However, no significant difference was found between 500N (non-twisted) and 500N (twisted) groups (p = 0.2645). Two samples broke from the distal femur growth plates, indicating potential growth plate vulnerability in adolescent porcines. Conclusions. The study validates the adolescent porcine stifle joint as a suitable model for ACL biomechanical research, demonstrating that torsional loads are as damaging to the ACL's integrity as equivalent axial loads. It also highlights the potential vulnerability of growth plates in younger populations, reflected in the porcine model

Background. Using flexible tethering techniques, porcine models of scoliosis have been previously described. These scoliotic curves showed vertebral wedging but very limited axial rotation. In some of these techniques, a persistent scoliotic deformity was found after tether release. The possibility to create severe progressive true scoliosis in a big animal model would be very useful for research purposes, including corrective therapies. Methods. The experimental ethics committee of the main institution provide the approval to conduct the study. Experimental study using a growing porcine model. Unilateral spinal bent rigid tether anchored to two ipsilateral pedicle screws was used to induce scoliosis on eight pigs. Five spinal segments were left between the instrumented pedicles. The spinal tether was removed after 8 weeks. Ten weeks later the animals were sacrificed. Conventional radiographs and 3D CT-scans of the specimens were taken to evaluate changes in the coronal and sagittal alignment of the thoracic spine. Fine-cut CT-scans were used to evaluate vertebral and disc wedging and axial rotation. Results. After 8 weeks of rigid tethering, the mean Cobb angle of the curves was 24.3 ± 13.8 degrees. Once the interpedicular tether was removed, the scoliotic curves progressed in all animals until sacrifice. During these 10 weeks without spinal tethering the mean Cobb angle reached 50.1 ± 27.1 degrees. The sagittal alignment of the thoracic spine showed loss of physiologic kyphosis. Axial rotation ranges from 10 to 35 degrees. There was no auto-correction of the curve in any animal. A further pathologic analysis of the vertebral segments revealed that animals with greater progression had more damage of the neurocentral cartilages and epiphyseal plates at the sites of pedicle screw insertion. Interestingly, in these animals with more severe curves, compensatory curves were found proximal and distal to the tethered segments. Conclusions. Temporary interpedicular tethering at the thoracic spine induces severe scoliotic curves in pigs, with significant wedging and rotation of the vertebral bodies. As detailed by CT morphometric analysis, release of the spinal tether systematically results in progression of the deformity with development of compensatory curves outside the tethered segment. The clinical relevance of this work is that this tether release model will be very useful to evaluate both fusion and non-fusion corrective technologies in future research. Level of Evidence. Not apply for experimental studies

The use of retrograde femoral intramedullary nails in children for deformity correction is controversial. It is unknown if the injury to the central part of the growth plate results in premature bony union, leading to limb deformities or discrepancies. The aim of this study was to assess physeal healing and bone growth after insertion of a retrograde femoral nail thorough the centre of the physis in a skeletally immature experimental porcine model. Eleven immature pigs were included in the study. One leg was randomised for operation with a retrograde femoral nail (diameter 10.7 mm), whilst the non-operated contralateral remained as control. All nails were inserted centrally in coronal and sagittal plane under fluoroscopic guidance, and the nails spanned the physis. The nails were removed at 8 weeks. Both femora in all animals underwent MRI at baseline (pre-operatively), 8 weeks (after nail removal) and 16 weeks (before euthanasia). Femoral bone length was measured at 5 sites (anterior, posterior, central, lateral and medial) using 3d T1-weighted MRI. Growth was calculated after 8 weeks (growth with nail) and 16 weeks (growth without nail). Physeal cross-sectional area and percentage violated by the nail was determined on MRI. Operated side was compared to non-operated. Corresponding 95% confidence intervals were calculated. No differences in axial growth were observed between operated and non-operated sides. Mean growth difference was 0,61 mm [−0,78;2,01] whilst the nail was inserted into the bone and 0,72 mm [−1,04;1,65] after nail removal. No signs of angular bone deformities were found when comparing operated side to non-operated side. No premature bony healing at the physis occurred. Histology confirmed fibrous healing. Mean physeal violation was 5.72% [5.51; 5.93] by the femoral nail. The insertion of a retrograde femoral nail through the centre of an open physis might be a safe procedure with no subsequent growth arrest. However, experiments assessing the long term physeal healing and growth are needed

The aim of this study was to validate the use of three models of fracture fixation in the assessment of technical skills. We recruited 21 subjects (six experts, seven intermediates, and eight novices) to perform three procedures: application of a dynamic compression plate on a cadaver porcine model, insertion of an unreamed tibial intramedullary nail, and application of a forearm external fixator, both on synthetic bone models. The primary outcome measures were the Objective Structural Assessment of technical skills global rating scale on video recordings of the procedures which were scored by two independent expert observers, and the hand movements of the surgeons which were analysed using the Imperial College Surgical Assessment Device. The video scores were significantly different for the three groups in all three procedures (p < 0.05), with excellent inter-rater reliability (α = 0.88). The novice and intermediate groups specifically were significantly different in their performance with dynamic compression plate and intramedullary nails (p < 0.05). Movement analysis distinguished between the three groups in the dynamic compression plate model, but a ceiling effect was demonstrated in the intramedullary nail and external fixator procedures, where intermediates and experts performed to comparable standards (p > 0.6). A total of 85% (18 of 21) of the subjects found the dynamic compression model and 57% (12 of 21) found all the models acceptable tools of assessment. This study has validated a low-cost, high-fidelity porcine dynamic compression plate model using video rating scores for skills assessment and movement analysis. It has also demonstrated that Synbone models for the application of and intramedullary nail and an external fixator are less sensitive and should be improved for further assessment of surgical skills in trauma. The availability of valid objective tools of assessment of surgical skills allows further studies into improving methods of training

Surgical reconstruction of articular surfaces by transplantation of osteochondral autografts has shown considerable promise in the treatment of focal articular lesions. During mosaicplasty, each cylindrical osteochondral graft is centred over the recipient hole and delivered by impacting the articular surface. Impact loading of articular cartilage has been associated with structural damage, loss of the viability of chondrocytes and subsequent degeneration of the articular cartilage. We have examined the relationship between single-impact loading and chondrocyte death for the specific confined-compression boundary conditions of mosaicplasty and the effect of repetitive impact loading which occurs during implantation of the graft on the resulting viability of the chondrocytes.

Fresh bovine and porcine femoral condyles were used in this experiment. The percentage of chondrocyte death was found to vary logarithmically with single-impact energy and was predicted more strongly by the mean force of the impact rather than by the number of impacts required during placement of the graft. The significance of these results in regard to the surgical technique and design features of instruments for osteochondral transplantation is discussed.

The treatment of osteochondral lesions and osteoarthritis remains an ongoing clinical challenge in orthopaedics. This review examines the current research in the fields of cartilage regeneration, osteochondral defect treatment, and biological joint resurfacing, and reports on the results of clinical and pre-clinical studies. We also report on novel treatment strategies and discuss their potential promise or pitfalls. Current focus involves the use of a scaffold providing mechanical support with the addition of chondrocytes or mesenchymal stem cells (MSCs), or the use of cell homing to differentiate the organism’s own endogenous cell sources into cartilage. This method is usually performed with scaffolds that have been coated with a chemotactic agent or with structures that support the sustained release of growth factors or other chondroinductive agents. We also discuss unique methods and designs for cell homing and scaffold production, and improvements in biological joint resurfacing. There have been a number of exciting new studies and techniques developed that aim to repair or restore osteochondral lesions and to treat larger defects or the entire articular surface. The concept of a biological total joint replacement appears to have much potential.

Cite this article: Bone Joint Res 2013;2:193–9.

Objectives

The period of post-operative treatment before surgical wounds are completely closed remains a key window, during which one can apply new technologies that can minimise complications. One such technology is the use of negative pressure wound therapy to manage and accelerate healing of the closed incisional wound (incisional NPWT).