Heterotopic ossification (HO) is defined as aberrant bone formation in extraskeletal locations. In this process, local stromal cells of mesenchymal origin abnormally differentiate, resulting in pathologic cartilage and bone matrix deposition. However, the specific cell type and mechanisms beyond this process are not well understood, in part due to the heterogeneity of progenitor cells involved. Here, a combination of single cell RNA sequencing (scRNA-Seq) and lineage tracing, defined the extent to which synovial / tendon sheath progenitor cells contribute to HO. For this purpose, a Tppp3 (tubulin polymerization-promoting protein family member 3) inducible reporter model was used, in combination with either Scx (Scleraxis) or Pdgfra (Platelet derived growth factor receptor alpha) reporter animals. Both arthroplasty-induced and tendon injury-mouse experimental HO models were utilized. ScRNA-Seq of tendon-induced traumatic HO suggested that Tppp3 is a progenitor cell marker for either osteochondral or tendon or cells. After HO induction, Tppp3 reporter+ cell population expanded in number and contributed to cartilage and bone formation in tendon and joint-associated HO. Using double reporter animals, we found that both Pdgfra+Tppp3+ and Pdgfra+Tppp3- progenitor cells produced HO-associated cartilage. Finally, the examination of human samples showed a significant population of TPPP3+ cells overlapping with osteogenic markers in areas of HO. Overall, these results provide novel observations that peritenon and synovial progenitor cells undergo abnormal osteochondral differentiation and contribute to heterotopic bone formation after trauma.
Heterotopic ossification is the formation of extraskeletal mineralized tissue commonly associated with either trauma or surgery. While several mouse models have been developed to better characterize the pathologic progression of HO, no model currently exists to study HO of the hip, the most common location of acquired HO in patients. Owing to the unique biological mechanisms underpinning the formation of HO in different tissues, we sought to develop a model to study the post-surgical HO of the hip. Wild-type mice C57BL/6J mice were used to study the procedure outcomes, while Pdgfra-CreERT2;mT/mG and Scx-GFP reporter animals were used for the lineage tracing experiments (total n=16 animals, male, 12 weeks old). An anterolateral approach to the hip was performed. Briefly, a 2 cm incision was made centered on the great trochanter and directed proximal to the iliac crest and distally over the lateral shaft of the femur. The joint was then reached following the intermuscular plane between the rectus femoris and gluteus medius muscles. After the joint was exposed, the articular cartilage was removed using a micropower drill with a 1.2 mm reamer. The medius gluteus and superficial fascia were then re-approximated with Vicryl 5-0 suture (Ethicon Inc, Somerville, NJ) and skin was then closed with Ethilon 5-0 suture (Ethicon Inc). Live high resolution XR imaging was performed every 2 wks to assess the skeletal tissues (Faxitron Bioptics, Tucson, AZ). The images were then scored using the Brooker classification. Ex-vivo microCT was conducted using a Skyscan 1275 scanner (Bruker-MicroCT, Kontich, Belgium). 3D reconstruction and analysis was performed using Dragonfly (ORS Inc., Montreal, Canada). For the histological analysis of specimens, Hematoxylin and Eosin (H&E), modified Goldner's Trichrome (GMT) stainings were performed. Reporter activity was assessed using fluorescent imaging.Introduction and Objective
Materials and Methods
Introduction. The management of periprosthetic pelvic bone loss is a challenging problem in hip revision surgery. This study evaluates the minimum 10-year clinical and radiographic outcome of major column structural allografts combined with the Burch-Schneider antiprotrusio cage for acetabular reconstruction. Methods. From January 1992 to August 2005, 106 hips with periprosthetic osteolysis underwent acetabular revision using massive allografts and the Burch-Schneider antiprotrusio cage. Forty-five patients (49 hips) died for unrelated causes without further surgery. Fifty-nine hips in 59 patients underwent clinical and radiographic evaluation at an average follow-up of 15.1 years. There were 17 male and 42 female patients, with age ranging from 29 to 83 years (mean 59). Results. Ten hips required rerevision because of infection (3), aseptic loosening (6), and flange breakage (1). Moreover, 4 cages showed x-ray signs of instability with severe bone resorption. The survivorship of the Burch-Schneider cage at 21.9 years with removal for any reason or radiographic migration and aseptic or radiographic failure as the end points were 76.3 and 81.4, respectively. The average Harris hip score improved from 33.2 points preoperatively to 75.7 points at the latest follow-up (
Total ankle replacement (TAR) is contraindicated in patients with significant talar collapse due to AVN and in these patients total talus body prosthesis has been proposed to restore ankle joint. To date, five studies have reported implantation of a custom-made talar body in patients with severely damaged talus, showing the limit of short-term damage of tibial and calcaneal thalamic joint surfaces. Four of this kind of implants have been performed. The first two realized with “traditional” technology CAD-CAM has been performed in active patients affected by “missing talus” and now presents a survival follow-up of 15 and 17 years. For the third patient affected by massive talus AVN we designed a 3D printed porous titanium custom talar body prosthesis fixed on the calcaneum and coupled with a TAR, first acquiring high-resolution 3D CT images of the contralateral healthy talus that was “mirroring” obtaining the volume of fractured talus in order to provide the optimal fit. Then the 3D printed implant was manufactured. The fourth concern a TAR septic mobilization with high bone loss of the talus. The “two-stage” reconstruction conducted with the implant of total tibio-talo-calcaneal prosthesis “custom made” built with the same technology 3D, entirely in titanium and using the “trabecular metal” technology for the calcaneous interface. Weightbearing has progressively allowed after 6 weeks. No complications were observed. All the implants are still in place with an overall joint mobility ranging from 40° to 60°. This treatment requires high demanding technical skills and experience with TAR and foot and ankle trauma. The 15 years survival of 2 total talar prosthesis coupled to a TAR manufactured by a CAD-CAM procedure encourages consider this 3D printed custom implant as a new alternative solution for massive AVN and traumatic missing talus in active patients.
