Laurent Sedel

Tissue-engineered bone regeneration.

Bone lesions above a critical size become scarred rather than regenerated, leading to nonunion. We have attempted to obtain a greater degree of regeneration by using a resorbable scaffold with regeneration-competent cells to recreate an embryonic environment in injured adult tissues, and thus improve clinical outcome. We have used a combination of a coral scaffold with in vitro-expanded marrow stromal cells (MSC) to increase osteogenesis more than that obtained with the scaffold alone or the scaffold plus fresh bone marrow. The efficiency of the various combinations was assessed in a large segmental defect model in sheep. The tissue-engineered artificial bone underwent morphogenesis leading to complete recorticalization and the formation of a medullary canal with mature lamellar cortical bone in the most favorable cases. Clinical union never occurred when the defects were left empty or filled with the scaffold alone. In contrast, clinical union was obtained in three out of seven operated limbs when the defects were filled with the tissue-engineered bone.

A biodegradable fibrin scaffold for mesenchymal stem cell transplantation.

A potential therapy to enhance healing of bone tissue is to deliver isolated mesenchymal stem cells (MSCs) to the site of a lesion to promote bone formation. A key issue within this technology is the development of an injectable system for the delivery of MSCs. Fibrin gel exploits the final stage of the coagulation cascade in which fibrinogen molecules are cleaved by thrombin, convert into fibrin monomers and assembled into fibrils, eventually forming fibers in a three-dimensional network. This gel could have many advantages as a cell delivery vehicle in terms of biocompatibility, biodegradation and hemostasis. The objective of this study was to explore the possibility of using fibrin gel as a delivery system for human MSCs (HMSCs). To this end we have determined the optimal fibrinogen concentrations and thrombin activity for loading HMSCs in vitro into the resultant fibrin gels to obtain cell proliferation. We found that a concentration of 18 mg/ml of fibrinogen and a thrombin activity of 100 IU/ml was optimal for producing fibrin scaffolds that would allow good HMSCs spreading and proliferation. In these conditions, cells were able to proliferate and expressed alkaline phosphatase, a bone marker, in vitro. When implanted in vivo, HMSCs were able to migrate out of the fibrin gel and invade a calcium carbonate based ceramic scaffold suggesting that fibrin gel could serve as a delivery system for HMSCs.

Alumina-on-alumina total hip arthroplasty: A minimum 18.5-year follow-up study

Background: The purpose of this retrospective study was to report the results, after a minimum of 18.5 years of follow-up, in a consecutive series of total hip arthroplasties performed with an alumina-on-alumina combination. Methods: One hundred and eighteen consecutive total hip arthroplasties were performed in 106 patients between 1979 and 1980. The prostheses combined a 32-mm alumina head and an all-alumina socket. Both components were cemented in eighty-five hips, both components were implanted without cement in twenty-nine, and only the stem was cemented in four. The mean age of the patients at the time of the index arthroplasty was 62.2 years (range, thirty-two to eighty-nine years). Results: At the 18.5 to 20.5-year follow-up evaluation, forty-five patients (fifty-one hips) were alive and had not had a revision, twenty-five patients (twenty-five hips) had undergone revision of one or both components, twenty-seven patients (thirty hips) had died, and nine patients (twelve hips) had been lost to follow-up. The mean Merle d’Aubigné hip score (and standard deviation) was 16.2 ± 1.8 points at the latest follow-up evaluation. The rate of survival at twenty years, with revision for any reason as the end-point, was 85.6% for the cementless cups compared with 61.2% for the cemented cups and 84.9% for the cementless stems compared with 87.3% for the cemented stems. Wear of the prosthetic components was undetectable on plain radiographs. Periprosthetic cystic or scalloped lesions requiring the use of allograft bone during revision were present in three of the twenty-five revised hips. In addition, seven hips had moderate acetabular osteolysis treated with a 4-mm-larger cup. No fracture of the alumina socket or head was recorded. The mean acetabular wear rate in this series was <0.025 mm/yr. Conclusion: With the alumina-on-alumina total hip arthroplasty, minimal wear rates and limited osteolysis can be expected up to twenty years after the operation, provided that sound acetabular component fixation is obtained.

Evolution of alumina-on-alumina implants: A review

The use of alumina-on-alumina sliding surfaces for total hip replacement is becoming increasingly popular. The author has reviewed the 30-year history of this material. Technical aspects such as the quality of the material, quality of the design, and the risk of fracture are presented. The clinical results observed by the author are summarized with additional references to the results of other surgeons. The overall conclusion is that this material is very safe if all the quality requirements are met. The extremely low generation of wear debris and the excellent biologic tolerance of the material impart a long lifetime to the implant in young and active patients.

Behavior of human osteoblastic cells on stoichiometric hydroxyapatite and type A carbonate apatite: Role of surface energy

To determine the role of physicochemical characteristics of the surface of dense ceramics on osteoconduction, we studied the proliferation and differentiation of human trabecular (HT) osteoblastic cells, extracellular collagenous matrix production, and biologic apatite formation on stoichiometric hydroxyapatite (HA) and type A carbonate apatite (CA). The surface physicochemical characteristics (composition, roughness) of HA and CA carefully were determined by Fourier-transformed infrared, X-ray photoelectron, and Raman spectroscopies, and by FTIR microscopy, before and after cell culture. On both HA and CA substrates, HT cells attached, proliferated, and differentiated. Cell proliferation did not differ on HA and CA. However, the initial cell attachment and spreading of HT cells were much lower on CA compared to HA. Physicochemical and biologic analyses showed that collagenous synthesis by HT cells after 6 weeks of culture also was lower on CA than on HA. Quantitative histologic analysis confirmed that the collagenous matrix production was lower on CA than on HA. Measurement of wettability showed that the polar interaction energy with water was significantly lower on CA than on HA. The lower cell attachment and collagen production on CA compared to HA clearly were related to the low affinity of HT cells for the CA surface. This study shows that the surface energy of the biomaterial greatly influences the initial cell attachment and spreading of human osteoblastic cells at the surface and affects collagenous matrix deposition on the biomaterial. This suggests that the enhancement of polar components of the surface of dense biomaterials may improve osteoblastic cell attachment and, thereby, osteoconduction.

Fractures of ceramic bearings: history and present status.

During a period of 25 years (1977 to 2001), 13 fractures of an alumina component were recorded retrospectively. During the same period, approximately 5500 alumina components were implanted (3300 with all-alumina bearings and 1200 with alumina-on-polyethylene). These events occurred in seven women and six men, with a mean age of 59 years and a mean weight of 71 kg. There were eight fractures of the femoral head and five fractures of the socket component. Three fractures clearly were related to trauma (two fractures of the socket and one fracture of the head) and two were related to an abnormal design (one 22-mm head and one extra-long neck). Five fractures occurred without any rational explanation, but two fractures that occurred in the early phase could have been caused by a weaker alumina material. Finally three recent fractures of the liner were related to a change in the design of the material. This has been corrected and no additional fractures were observed. Although this dramatic event is of concern, it is infrequent and easy to solve by a limited revision procedure if done emergently. This rare complication should be balanced with the other complications of THR, including mechanical failures and osteolysis, often described with metal-on-polyethylene prostheses.

Ten-year survivorship of cemented ceramic-ceramic total hip prosthesis.

In the first 187 consecutive alumina-alumina combination hip arthroplasties performed from 1977 to 1979, both components were cemented with conventional techniques. At ten-year follow-up evaluation, 87 patients were reviewed or interviewed by telephone, 37 were dead, 39 were lost to follow-up evaluation, and 24 failures were reoperated on before the end of ten years. The major cause of failure was aseptic loosening of the acetabular component (15 failures). Fracture of the socket and of the femoral head occurred in five patients in this series. However, these complications were not seen with components manufactured after 1979. At the end of ten years, survivorship analysis depicted a 82.59% survival rate when reoperation was considered as failure and a 88.57% rate when reoperation for aseptic loosening was considered as failure. The femoral component had a 99.16% survival rate and the acetabular component had an 88.57% survival rate when reoperation for aseptic loosening was considered as failure. Age, appearance of a two- or three-zone demarcation at the intermediate follow-up evaluation, and outer diameter of the acetabular component were the major parameters influencing the results. Better results observed in the population younger than 50 years of age may be related to the small amount of wear debris produced by the alumina-alumina combination. This combination in hip prosthesis is secure, but should be implanted in young and active patients; the outer diameter of the acetabular component must be at least 50 mm. The major problem that remains is the sockets fixation. It could be improved by a design modification, by choosing another mode of fixation, or both.

Complete Traumatic Brachial Plexus Palsy. Treatment and Outcome After Repair

Seventy-eight patients who had a complete brachial plexus palsy caused by a stretching injury were operated on by the same surgeon between January 1980 and December 1991. The aim of the operative intervention was to obtain the best functional result, including at the level of the hand, that was possible in view of the initial lesions and the intraoperative findings. Therefore, the treatment strategy included not only nerve repair with grafting (124 grafts) or nerve transfer (twenty-seven transfers) but also palliative procedures, the latter of which sometimes were performed several years later. Sixty-three patients were evaluated by an independent observer at least three years postoperatively. The results associated with each type of lesion and each type of nerve repair were assessed according to the function of the muscles that were innervated by the recipient nerve. Six patients had a neurolysis only. The remaining fifty-seven patients had grafts or nerve transfers to repair the biceps. Thirty-six of the fifty-seven received a rating of 3+ or more (meaning that the patient was able to flex the elbow repeatedly); the remaining twenty-one received a rating of 3 or less (meaning that the patient was able to flex the elbow only once or not at all), which we considered unsatisfactory. The function of the triceps recovered after eleven of thirty-one procedures that were performed to restore that nerve; that of the extensor carpi radialis, after five of thirty-one procedures; that of the flexor carpi radialis, after six of thirty-one procedures; and that of the flexor digitorum, after four of thirty-one procedures. A statistical analysis revealed that an operative delay of less than six months was a significant factor with respect to recovery of the function of the biceps (p = 0.003). The thirty-nine grafts that were sutured onto the lateral or posterior cord produced better results than did the thirty-six that were sutured onto the distal branches (the musculocutaneous and radial nerves); however, with the numbers available, this difference was not found to be significant (p = 0.08). Eleven patients had a successful result (a rating of 3+ or more) and eight, a fair or poor result, with respect to recovery of biceps function after transfer of the spinal accessory nerve to the musculocutaneous nerve. Overall, twenty-nine patients had relief of pain postoperatively. Sixteen patients had grade-3 pain preoperatively compared with only three after the operation. According to a self-rating scale, twenty-five patients were satisfied with the overall result, sixteen were fairly satisfied, and twenty-two were dissatisfied.

Effects of chitosan on rat knee cartilages

The aim of this work is to study the effects of chitosan on rat knee cartilages. 0.2 ml of 0.1% chitosan solution pH = 6.9 were injected inside rat knees articular cavity. One, three and six weeks after injection, histological and histomorphometric studies were performed on undecalcified samples embedded in polymethylmetacrylate. Results show that after 1 and 6 weeks: (i) chitosan slows significantly (P < 0.005) the decrease in epiphyseal cartilage thicknesses and (ii) increases significantly articular cartilage chondrocyte densities (P < 0.002). However chitosan solution induces a proliferation of fibrous tissue with abundant fibroblasts, fibrocytes and monocytes inside the joint and this proliferation is still present after 6 weeks. This study suggests that chitosan could act on the growth of epiphyseal cartilage and wound healing of articular cartilage.

A meta-analysis of patellar replacement in total knee arthroplasty

From individual randomized studies it is unclear whether the patella should be replaced during total knee replacement. We did a meta-analysis to provide quantitative data to compare patellar resurfacing with nonresurfacing during total knee arthroplasty. Only randomized, controlled trials reported between January 1966 and August 2003 comparing patellar replacement with patella retention were included for a total of 12 studies. Two reviewers assessed trial quality and extracted data from papers. The outcomes identified were reoperations for patellar problems, anterior knee pain, knee scores, stair climbing, and patient satisfaction. The resurfaced patella performed better, and we found an increased relative risk (defined by the ratio of the risk of the event in the resurfaced group on the risk of the event in the nonresurfaced group) for reoperation, for significant anterior knee pain, and for significant pain during stair climbing when the patella was left unresurfaced. No differences were observed between the two groups for International Knee Society function score, Hospital for Special Surgery score, and for patient satisfaction. Despite these general findings, forming a definitive conclusion is difficult because many confounding factors, such as component design, surgeon experience, and technical aspects of the surgery, might influence the result in a patient. Level of Evidence: Therapeutic study, Level II-3 (systematic review. b. Nonhomogeneous Level I studies)