Pediatric Malignant Mandibular Tumors: Personal Experience and Literature Options Discussion.

INTRODUCTION: Mandibular defects reconstruction could result challenging in childhood, due to facial and mandibular growth patterns. For these reasons, the choice of the most suitable reconstructive option in pediatric patients, affected by mandibular malignancies, still objects of debate. OBJECTIVE: The aim of our study was to compare our reconstructive schedules to the existing literature in order to give a personal contribute to the present panorama. METHODS: We performed, in October 2019, a retrospective evaluation of pediatric patients treated for biopsy-proven mandibular malignancies at our Institute between January 2013 and December 2016. All of them received multimodal therapy in accordance with standard guidelines and their demographic, clinical, treatment, and outcome parameters were collected and analyzed. RESULTS: We observed a shorter duration of surgery, a faster tracheostomy tube and feeding-tube removal, and a minor hospitalization in patients who received grafts transfer compared to those who underwent microsurgical mandibular reconstruction. After a 36-month period of follow-up, osteochondral grafts showed a pattern of growth similar to the mandibular epiphysis (condilylion-gonion linear and vertical ratio ranging to 0.96-1.03 and 1-1.02 at orthopantomogram, respectively). No bone consolidation delays and functional impairment were recorded. CONCLUSIONS: Free flaps mandibular reconstruction in children needs to be better assessed and proximal fibular epiphyseal free flap indication might deserve further studies. Osteochondral grafts find indication for lateral defects, 50-55 mm in maximum length and located in the mandibular ramus, without massive teeth or soft tissue defect. Condyle involvement does not represent an absolute contraindication to rib graft use.

Promising outcomes of hip mosaicplasty by minimally invasive anterior approach using osteochondral autografts from the ipsilateral femoral head.

PURPOSE: Recent studies demonstrated promising results of mosaicplasty for femoral head osteochondral lesions using posterior and lateral approaches. This study aimed to evaluate outcomes of mosaicplasty using ipsilateral femoral head autografts by minimally invasive anterior approach. The hypothesis was that this surgical technique would grant satisfactory clinical outcomes with considerable improvement of clinical scores. METHODS: A consecutive series of 27 mosaicplasties, to treat osteochondral lesions of the femoral head measuring 1.6 ± 0.7 cm2 (range 0.8-4.0) in patients aged 28.7 ± 7.4 years (range 19-44), was evaluated using the mHHS and WOMAC scores at minimum follow-up of 12 months. All patients were operated by minimally invasive anterior (Hueter) approach and osteochondral plugs were harvested from the non-weight-bearing portion of the femoral head. Adjuvant osteoplasty was necessary for some patients at the acetabulum (n = 3), femur (n = 14) or both (n = 2). RESULTS: Three patients were excluded due to concomitant periacetabular osteotomies or shelf procedures, one patient could not be reached, and another was revised to THA. This left 22 patients for clinical assessment at 39.4 ± 23.2 months (12.0-90.2). Their mHHS improved from 56.3 ± 12.6 to 88.4 ± 9.9, and WOMAC improved from 45.1 ± 16.9 to 80.6 ± 13.0. Two patients (8.4%) underwent arthroscopy at 13 and 30 months to remove painful residual cam-type deformities. Regression analyses revealed that net improvement in WOMAC decreased with lesion size (p = 0.002) and increased with follow-up (p = 0.004). CONCLUSIONS: Hip mosaicplasty using autografts from the ipsilateral femoral head, performed by minimally invasive anterior approach, granted satisfactory outcomes and functional improvements. Caution is, however, advised for lesions > 2 cm2 (diameter > 16 mm) which may be a threshold limit for this procedure. LEVEL OF EVIDENCE: Level IV, Case series.

Nonvascularized Cartilage Grafts Versus Vascularized Cartilage Flaps: Comparison of Cartilage Quality 6 Months After Transfer.

PURPOSE: Subchondral perfusion of osteochondral grafts has been shown to be important in preventing long-term cartilage degeneration. In carpal reconstruction, subchondral perfusion from the graft bed is limited. This study's purpose was to compare the histological characteristics of cartilage in osteochondral grafts supported by synovial imbibition alone to cartilage of vascularized osteochondral flaps that have both synovial and vascular pedicle perfusion. METHODS: Two adjacent osteochondral segments were harvested on the medial femoral trochlea in domestic 6- to 8-month-old pigs. Each segment measured approximately 12 mm × 15 mm × 17 mm. One segment was maintained on the descending geniculate artery vascular pedicle. The adjacent segment was separated from the pedicle to serve as a nonvascularized graft. A thin layer of methylmethacrylate cement was used to line the harvest site defect to prevent vascular ingrowth to the subsequently replaced specimens. The pigs were maintained on a high-calorie feed and returned to ambulation and full weight-bearing on the surgical legs. The animals were sacrificed after 6 months and the specimens were reharvested, sectioned, and examined. The cartilage was graded by 2 pathologists blinded to the origin of specimens as vascularized flaps or nonvascularized grafts. RESULTS: All specimens were assigned scores utilizing the International Cartilage Repair Society grading system. Scoring for chondrocyte viability, cartilage surface morphology, and cell and matrix appearance was significantly higher in the vascularized osteochondral group than in the graft group. CONCLUSIONS: When deprived of subchondral perfusion from underlying bone, osteochondral vascularized flaps in an intrasynovial environment demonstrate superior cartilage quality and survival compared with nonvascularized grafts. CLINICAL RELEVANCE: In locations in which perfusion from surrounding bone may be limited (ie, proximal scaphoid or proximal lunate reconstruction), articular reconstruction using vascularized osteochondral flaps will yield superior cartilage organization and architecture than nonvascularized osteochondral grafts. The clinical and functional relevance of this finding requires further study.

Osteonecrosis of the knee - which joint preservation procedures work?

There is no consensus with respect to the best procedures to preserve the knee joint in patients with osteonecrosis of the knee. We performed a systematic review of the literature between 1999 and 2012. Only 10 of 1057 studies met our inclusion criteria. Core decompression prevented additional surgical treatment in pre-collapse knees with a failure rate of 10.4% (7 of 67 knees). Autogenous and osteochondral grafts decreased the need for additional surgery in both pre-collapse (0%, 20 of 20) and post-collapse knees (10.5%, 8 of 76 knees). Although these results are quite promising multi-center randomized trials are needed to identify the optimal procedures to treat this disease.

Microscale strain concentrations in tissue-engineered osteochondral implants are dictated by local compositional thresholds and architecture.

Tissue-engineered osteochondral implants manufactured from condensed mesenchymal stem cell bodies have shown promise for treating focal cartilage defects. Notably, such manufacturing techniques have shown to successfully recapture the bulk mechanical properties of native cartilage. However, the relationships among the architectural features, local composition, and micromechanical environment within tissue-engineered cartilage from cell-based aggregates remain unclear. Understanding such relationships is crucial for identifying critical parameters that can predict in vivo performance. Therefore, this study investigated the relationship among architectural features, composition, and micromechanical behavior of tissue-engineered osteochondral implants. We utilized fast-confocal microscopy combined with a strain mapping technique to analyze the micromechanical behavior under quasi-static loading, as well as Fourier Transform Infrared Spectroscopy to analyze the local compositions. More specifically, we investigated the architectural features and compositional distributions generated from tissue maturation, along with macro- and micro-level strain distributions. Our results showed that under compression, cell-based aggregates underwent deformation followed by body movement, generating high local strain around the boundaries, where local aggrecan concentration was low and local collagen concentration was high. By analyzing the micromechanics and composition at the single aggregate length scale, we identified a strong threshold relationship between local strain and compositions. Namely at the aggrecan concentration below 0.015 arbitrary unit (A.U.) and the collagen concentration above 0.15 A.U., the constructs experienced greater than threefold increase in compressive strain. Overall, this study suggests that local compositional features are the primary driver of the local mechanical environment in tissue-engineered cartilage constructs, providing insight into potential quality control parameters for manufacturing tissue-engineered constructs.

Osteochondral tissue engineering in translational practice: histological assessments and scoring systems.

Osteochondral lesions are common pathological alterations in synovial joints. Different techniques have been designed to achieve osteochondral repair, and tissue-engineered osteochondral grafts have shown the most promise. Histological assessments and related scoring systems are crucial for evaluating the quality of regenerated tissue, and the interpretation and comparison of various repair techniques require the establishment of a reliable and widely accepted histological method. To date, there is still no consensus on the type of histological assessment and scoring system that should be used for osteochondral repair. In this review, we summarize common osteochondral staining methods, discuss the criteria regarding high-quality histological images, and assess the current histological scoring systems for osteochondral regeneration. Safranin O/Fast green is the most widely used staining method for the cartilage layer, whereas Gomori and Van Gieson staining detect new bone formation. We suggest including the graft-host interface and more sections together with the basic histological information for images. An ideal scoring system should analyze both the cartilage and bone regions, especially for the subchondral bone plate. Furthermore, histological assessments should be performed over a longer period of time to minimize discrepancies caused by defect size and animal species.

Proximal Scaphoid Reconstruction Techniques Comparison of Three Techniques for Proximal Scaphoid Recontruction.

Introduction The costo-osteochondral autograft, vascularized medial femoral trochlear osteochondral autograft, and proximal hamate autograft have been used for the reconstruction of unsalvageable proximal pole scaphoid nonunions. Our hypothesis is that there is no difference in carpal kinematics after the proximal pole of the scaphoid is reconstructed with these three graft options. Methods Wireless sensors were mounted to the carpus that was loaded through cyclical motion. Each specimen was tested under a series of the three reconstructed conditions and their kinematics compared. Results No significant differences were found in scapholunate and lunocapitate joint motion during wrist flexion-extension and wrist radioulnar deviation between the three reconstructed conditions ( p > 0.05). Discussion and Conclusion There are minimal differences in carpal kinematics when comparing reconstruction of the proximal pole of the scaphoid with the costoosteochondral, medial femoral trochlear, and proximal hamate grafts.

Osteochondral autologous transplantation for large steroid-induced osteonecrosis lesion of the knee in a young patient yielding satisfactory results despite only partial coverage: a case report.

Osteochondral autologous transplantation (OAT) is one of the most common surgical options for osteochondral disorders of the knee. In cases where OAT is performed for steroid-induced osteonecrosis, there are several problems potentially affecting the surgical outcomes such as large chondral damage area and compromised host bone. In addition, steroid administration for a long period of time may lead to extensive lesion, which poses difficulty in obtaining sufficient donor tissue. Those factors affect the prognosis of steroid-induced osteonecrosis resulting in inferior treatment outcomes. We present a young female with a large steroid-induced osteonecrosis lesion repaired only with two osteochondral plugs harvested from the healthy area. The reported case indicates that only partial osteochondral grafting limiting to the weight-bearing area may yield satisfactory outcome when OAT is performed for large steroid-induced osteonecrosis of the knee.

A Comparative Study Using Fluorescent Confocal Microscopy and Flow Cytometry to Evaluate Chondrocyte Viability in Human Osteochondral Allografts.

The preservation conditions of fresh osteochondral allografts for clinical applications are critical due their objective: to transplant mature hyaline cartilage containing viable chondrocytes, maintaining their metabolic activity and also preserving the structural and functional characteristics of the extracellular matrix. The aim of the present study was to compare fluorescence confocal microscopy and flow cytometry techniques to evaluate the viability of the chondrocytes present in the osteochondral tissue, in order to determine their effectiveness and thus ensure reproducibility and robustness of the analysis. To this end, osteochondral allografts from human cadaveric donors were preserved at 4 °C for 3 weeks in a preservation medium supplemented with antibiotic and antifungal agents. Cell viability of chondrocytes was determined by monitoring the cartilage for 3 weeks of preservation by confocal fluorescence microscopy and flow cytometry, obtaining cell viabilities of 83.7 ± 2.6% and 55.8 ± 7.8% for week three, respectively. The confocal fluorescence microscopy approach is more advantageous and accurate, as it correlates better with actual cell viability values for monitoring osteochondral graft preservation, detecting only the cells that died a natural death associated with the preservation method.

Midterm Outcomes of Autologous Osteochondral Graft Transplantation Only in the Femoral Condyle without Treating the Tibial Plateau with Subchondral Bone Exposed.

OBJECTIVE: This study aimed to examine the midterm clinical outcomes of autologous osteochondral grafts (AOG) that were performed in the femoral condyle without treating the tibial plateau with subchondral bone exposed, and to compare these outcomes with those of AOG used in patients with osteoarthritis (lateral type or medial type) or osteonecrosis. DESIGN: The study included 6 men and 16 women and 11 right knees and 11 left knees. The mean operative age was 56.0 years (range, 21-76 years), and the mean follow-up period was 98.4 months (range, 60-164 months). Six patients had lateral type osteoarthritis (OAL), 7 had medial type osteoarthritis (OAM), and 9 had osteonecrosis (ON). The patients' knee symptoms as their clinical outcome were evaluated using the knee scoring system of the Japanese Orthopedic Association (JOA), and the International Knee Documentation Committee (IKDC) subjective score. RESULTS: The postoperative clinical outcomes of the OAL and ON group were significantly better than their preoperative clinical scores and remained the same until the final follow-up. However, the clinical outcomes of OAM improved 2 years after AOG, but eventually decreased thereafter. The number of worse cases in the OAM group was significantly larger than those in the OAL and ON groups. CONCLUSION: In these procedures, the postoperative clinical outcomes of the OAL and ON groups were significantly better than their preoperative clinical scores and were maintained for about 8 years. However, the clinical outcomes of OAM improved until 2 years after AOG, but eventually decreased thereafter.

Vitrification of porcine articular cartilage.

The limited availability of fresh osteochondral allograft tissues necessitates the use of banking for long-term storage. A vitrification solution containing a 55% cryoprotectant formulation, VS55, previously studied using rabbit articular cartilage, was evaluated using porcine articular cartilage. Specimens ranging from 2 to 6 mm in thickness were obtained from 6mm distal femoral cartilage cores and cryopreserved by vitrification or freezing. The results of post-rewarming viability assessments employing alamarBlue demonstrated a large decrease (p<0.001) in viability in all three sizes of cartilage specimen vitrified with VS55. This is in marked contrast with prior experience with full thickness, 0.6 mm rabbit cartilage. Microscopic examination following cryosubstitution confirmed ice formation in the chondrocytes of porcine cartilage vitrified using VS55. Experiments using a more concentrated vitrification formulation (83%), VS83, showed a significant treatment benefit for larger segments of articular cartilage. Differences between the VS55 and the VS83 treatment groups were significant at p<0.001 for 2 mm and 4 mm plugs, and at p<0.01 for full thickness, 6 mm plugs. The percentage viability in fresh controls, compared to VS55 and VS83, was 24.7% and 80.7% in the 2 mm size group, 18.2% and 55.5% in the 4 mm size group, and 5.2% and 43.6% in the 6 mm group, respectively. The results of this study continue to indicate that vitrification is superior to conventional cryopreservation with low concentrations of dimethyl sulfoxide by freezing for cartilage. The vitrification technology presented here may, with further process development, enable the long-term storage and transportation of living cartilage for repair of human articular surfaces.

High intensity focused ultrasound as a tool for tissue engineering: Application to cartilage.

This article promotes the use of High Intensity Focused Ultrasound (HIFU) as a tool for affecting the local properties of tissue engineered constructs in vitro. HIFU is a low cost, non-invasive technique used for eliciting focal thermal elevations at variable depths within tissues. HIFU can be used to denature proteins within constructs, leading to decreased permeability and potentially increased local stiffness. Adverse cell viability effects remain restricted to the affected area. The methods described in this article are explored through the scope of articular cartilage tissue engineering and the fabrication of osteochondral constructs, but may be applied to the engineering of a variety of different tissues.

Challenges in engineering osteochondral tissue grafts with hierarchical structures.

INTRODUCTION: A major hurdle in treating osteochondral (OC) defects is the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. AREAS COVERED: This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. EXPERT OPINION: A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens and harnessing of inflammatory responses of the host will likely drive the further progress.

Porous titanium bases for osteochondral tissue engineering.

Tissue engineering of osteochondral grafts may offer a cell-based alternative to native allografts, which are in short supply. Previous studies promote the fabrication of grafts consisting of a viable cell-seeded hydrogel integrated atop a porous, bone-like metal. Advantages of the manufacturing process have led to the evaluation of porous titanium as the bone-like base material. Here, porous titanium was shown to support the growth of cartilage to produce native levels of Young's modulus, using a clinically relevant cell source. Mechanical and biochemical properties were similar or higher for the osteochondral constructs compared to chondral-only controls. Further investigation into the mechanical influence of the base on the composite material suggests that underlying pores may decrease interstitial fluid pressurization and applied strains, which may be overcome by alterations to the base structure. Future studies aim to optimize titanium-based tissue engineered osteochondral constructs to best match the structural architecture and strength of native grafts. STATEMENT OF SIGNIFICANCE: The studies described in this manuscript follow up on previous studies from our lab pertaining to the fabrication of osteochondral grafts that consist of a bone-like porous metal and a chondrocyte-seeded hydrogel. Here, tissue engineered osteochondral grafts were cultured to native stiffness using adult chondrocytes, a clinically relevant cell source, and a porous titanium base, a material currently used in clinical implants. This porous titanium is manufactured via selective laser melting, offering the advantages of precise control over shape, pore size, and orientation. Additionally, this manuscript describes the mechanical influence of the porous base, which may have applicability to porous bases derived from other materials.