Hip revision surgery in cases with acetabular bone loss: PPR rings, homologous bone and platelet gel

Abstract Hip revision has several objectives: filling the bone defect, restoring the rotational center of the hip, and restoring limb length and hip function. Recently, through tissue engineering, it became possible to consider a fourth objective: to give a graft improved capability to osteointegrate and to restore bone stock as for amount of bone and bone quality (tissue engineering or bioenhancement). Concerning biomechanical and clinical objectives, rings are the most commonly used prosthesis. We used the Partial Pelvic Replacement (PPR) ring and retrospectively analyzed our patients at a mean follow-up of 27.2 months. We found no signs of radiological failure, no radiolucency or osteolysis, nor implant component ruptures. The mean Harris hip score improved significantly from 35.9 preoperatively to 78.1. As for the anatomical objective of hip revision surgery, homologous bone grafts are the most used means to fill a bone defect. We developed a new method to produce platelet gel as a simple and inexpensive way to obtain autologous growth factors, without any discomfort for the patient. We used platelet gel with PPR rings and homologous bone graft; we report our method and describe the first cases treated, with good results.     

Platelet concentrate increases bone ingrowth into porous hydroxyapatite

Platelets contain growth factors that are believed to stimulate early fracture repair. Autologous platelets can be sequestered, concentrated, and mixed with thrombin to yield a so-called autologous growth factor gel, which might enhance bone repair or bone graft incorporation. The effect of this platelet concentrate on total tissue and bone ingrowth into porous coralline hydroxyapatite was studied in a bone chamber rat model. Chambers with the platelet concentrate showed a significant increase in bone and total tissue ingrowth distance compared to untreated controls, indicating a platelet concentrate might enhance the clinical performance of porous hydroxyapatite in bone replacement.     

A study of 23 unicameral bone cysts of the calcaneus: open chip allogeneic bone graft versus percutaneous injection of bone powder with autogenous bone marrow

BACKGROUND: The treatment of unicameral bone cyst varies from percutaneous needle biopsy, aspiration and local injection of steroid, autologous bone marrow, or demineralized bone matrix to curettage and open bone-grafting. The purpose of this study was to compare the results of open chip allogeneic bone graft versus percutaneous injection of demineralized bone powder with autogenous bone marrow in management of calcaneal cysts. MATERIALS AND METHODS: Twenty-three calcaneal unicameral cysts in 20 patients were treated. Lyophilized irradiated chip allogeneic bone (CAB) and autogenous bone marrow were used for treatment of 13 cysts in 11 patients, and 10 cysts in 9 patients were treated with percutaneous injection of irradiated allogeneic demineralized bone powder (DBP) and autogenous bone marrow. There were 11 males and 9 female patients with mean age of 17 years. RESULTS: The patients were followed for an average of 49.4 months. Complete healing was achieved in 9 cysts treated with chip allogeneic bone and in 5 cysts treated with powdered bone. Four cysts treated with CAB and 3 cysts treated with DBP healed with a defect. Two cysts treated with powdered bone and autogenous bone marrow were classified as persistent. No infections or pathological fractures were observed during the followup period. CONCLUSION: Percutaneous injection of a mixture of allogeneic bone powder with autogenous bone marrow is a minimal invasive method and could be an effective alternative in the treatment of unicameral calcaneal bone cysts. The postoperative morbidity was low, the hospital stay was brief, and patient's comfort for unrestricted activity was enhanced.     

Major bone defect treatment with an osteoconductive bone substitute

A bone defect can be provoked by several pathological conditions (e.g. bone tumours, infections, major trauma with bone stock loss) or by surgical procedures, required for the appropriate treatment. Surgical techniques currently used for treating bone defects may count on different alternatives, including autologous vascularized bone grafts, homologous bone graft provided by musculoskeletal tissue bank, heterologous bone graft (xenograft), or prostheses, each one of them dealing with both specific advantages and complications and drawbacks. The main concerns related to these techniques respectively are: donor site morbidity and limited available amount; possible immune response and viral transmission; possible animal-derived pathogen transmission and risk of immunogenic rejection; high invasiveness and surgery-related systemic risks, long post-operative. physical recovery and prostheses revision need. Nowadays, an ideal alternative is the use of osteoconductive synthetic bone substitutes. Many synthetic substitutes are available, used either alone or in combination with other bone graft. Synthetic bone graft materials available as alternatives to autogeneous bone include calcium sulphates, special glass ceramics (bioactive glasses) and calcium phosphates (calcium hydroxyapatite, HA; tricalcium phosphate, TCP; and biphasic calcium phosphate, BCP). These materials differ in composition and physical properties fro each other and from bone (De Groot in Bioceramics of calcium phosphate, pp 100–114, 1983; Hench in J Am Ceram Soc 74:1487–1510, 1994; Jarcho in Clin Orthop 157:259–278, 1981; Daculsi et al. in Int Rev Cytol 172:129–191, 1996). Both stoichiometric and non-stoichiometric HA-based substitutes represent the current first choice in orthopedic surgery, in that they provide an osteoconductive scaffold to which chemotactic, circulating proteins and cells (e.g. mesenchymal stem cells, osteoinductive growth factors) can migrate and adhere, and within which progenitor cells can differentiate into functioning osteoblasts (Szpalski and Gunzburg in Orthopedics 25S:601–609, 2002). Indeed, HA may be extemporarily combined either with whole autologous bone marrow or PRP (platelet rich plasma) gel inside surgical theatre in order to favour and accelerate bone regeneration. A case of bifocal ulnar bone defect treated with stoichiometric HA-based bone substitute combined with PRP is reported in here, with a 12-month-radiographic follow-up.     

Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect

BACKGROUND: Mesenchymal stem cells from adult bone marrow are multipotent cells capable of forming bone, cartilage, and other connective tissues. In a previous study, we demonstrated that autologous mesenchymal stem cells could repair a critical-sized bone defect in the dog. The objective of this study was to determine whether the use of allogeneic mesenchymal stem cells could heal a critical-sized bone defect in the femoral diaphysis in dogs without the use of immunosuppressive therapy. METHODS: A critical-sized segmental bone defect, 21 mm in length, was created in the mid-portion of the femoral diaphysis of twelve adult dogs that weighed between 22 and 25 kg. Each defect was treated with allogeneic mesenchymal stem cells loaded onto a hollow ceramic cylinder consisting of hydroxyapatite-tricalcium phosphate. A complete mismatch between donor stem cells and recipient dogs was identified by dog leukocyte antigen typing prior to implantation. The healing response was evaluated histologically and radiographically at four, eight, and sixteen weeks after implantation. The radiographic and histological results at sixteen weeks were compared with the historical data for the control defects, which included defects that had been treated with a cylinder loaded with autologous mesenchymal stem cells, defects treated with a cylinder without mesenchymal stem cells, and defects that had been left untreated (empty). The systemic immune response was evaluated by the analysis of recipient serum for production of antibodies against allogeneic cells. RESULTS: For defects treated with allogeneic mesenchymal stem cell implants, no adverse host response could be detected at any time-point. Histologically, no lymphocytic infiltration occurred and no antibodies against allogeneic cells were detected. Histologically, by eight weeks, a callus spanned the length of the defect, and lamellar bone filled the pores of the implant at the host bone-implant interface. Fluorescently labeled allogeneic cells were also detected. At sixteen weeks, new bone had formed throughout the implant. These results were consistent with those seen in implants loaded with autologous cells. Implants loaded with allogeneic or autologous stem cells had significantly greater amounts of bone within the available pore space than did cell-free implants at sixteen weeks (p < 0.05). CONCLUSIONS: The results of this study demonstrated that allogeneic mesenchymal stem cells loaded on hydroxyapatite-tricalcium phosphate implants enhanced the repair of a critical-sized segmental defect in the canine femur without the use of immunosuppressive therapy. No adverse immune response was detected in this model.     

人工骨联合自体骨髓移植技术的骨缺损修复研究与应用

目的分析人工骨联合自体骨髓移植技术治疗骨缺损的临床疗效。方法选取2011年4月至2013年9月,来本院诊治的四肢粉碎性骨折术后骨缺损患者40例,随机分为两组（A、B组）,分别行自体髂骨植骨和人工骨联合自体骨髓移植治疗四肢粉碎性骨折所致骨缺损。术后观察两组骨折愈合时间,骨折愈合率,并发症的发生及骨缺损的修复和功能重建优良率。结果两组均行6～12个月随访,平均（9.14±1.36）月,所有患者植骨术后均无切口感染、发热等并发症。A组15例骨缺损区愈合良好,住院时间平均（19.36±2.54）天,骨折愈合时间平均（5.67±1.52）个月,骨缺损的修复和功能重建评价标准,优12例,良3例,可3例,差2例,优良率75%;B组18例骨缺损区愈合良好,住院时间平均（12.19±1.52）天,骨折愈合时间平均（3.61±1.13）个月,骨缺损的修复和功能重建评价标准,优16例,良2例,可2例,差0例,优良率90%。B组骨缺损治疗效果显著优于A组。结论人工骨联合自体骨髓移植较单纯自体髂骨移植治疗骨缺损更能促进骨痂生长,加速骨折后骨缺损愈合,更加有效地减少住院时间及骨折愈合时间,骨折愈合率更高,骨缺损修复和功能重建效果更加显著。     

Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs

The use of platelet-rich plasma (PRP) for improving of bone defect healing is discussed controversially. The aim of this study was to assess the effect of PRP in combination with autologous cancellous graft on bone defect healing in a critical metaphyseal long bone defect. A critical size defect in the tibial metaphysis of 16 mini-pigs was filled either with autologous cancellous graft as control group or with autologous cancellous graft combined with autologous PRP. Compared to native blood platelets were enriched about 4.9-fold in the PRP. After 6 weeks, the specimens were assessed by X-ray and histological evaluation. Histomorphometrical analysis revealed that the area of new bone was significantly higher in the PRP group concerning the central area of the defect zone (p < 0.02) as well as the cortical defect zone (p < 0.01). All defects showed substantial new bone formation, but only defects of the PRP group regenerated entirely. The PRP group was superior to the control group even in the semi-quantitative assessment of the osseous bridging in both observed areas of the defect. Within the limits of the present study it could be demonstrated that PRP combined with autologous cancellous graft leads to a significantly better bone regeneration compared to isolated application of autologous cancellous graft in an in vivo critical size defect on load-bearing long bones of mini-pigs.     

组织工程化同种异体骨移植修复骨缺损

目的解决骨缺损修复时自体骨移植存在修复材料来源有限,异体骨移植又为爬行替代,存在愈合慢、假关节率高的问题。方法以兔骨膜成骨细胞为种子细胞,经分离、体外培养、传代,再粘附于冷冻干燥表面脱钙同种异体骨,共同复合培养,制作兔胫骨缺损,分异体骨移植组(对照组)、组织工程化异体骨移植组,术后2、4、6周各处死2只兔子,大体观测骨痂大小及硬度;苏木精-伊红染色,光镜观察细胞在材料上的生长情况,了解其愈合快慢及质量。结果与对照组比较,实验组炎性明显较轻,细胞生长活跃,缺损愈合快。结论组织工程化同种异体骨移植能解决骨缺损修复时自体植骨材料来源有限,特别是在小儿及骨缺损大时修复材料的来源问题;同时,植入的异体骨又具有支架及自体成骨细胞活性,使植入的异体骨愈合加快,克服其愈合慢、假关节率高的问题。     

Controlled release of platelet growth factors enhances bone regeneration at rabbit calvaria.

OBJECTIVE: Platelet-rich plasma (PRP) has been clinically employed to promote bone regeneration. However, few studies have investigated the enhancement of biological function of platelet growth factors after integration of PRP into biomaterials. In this study, the feasibility of gelatin hydrogels for controlled release of platelet growth factors and the consequent enhancement of PRP-induced bone regeneration were evaluated in rabbit calvarial defect. STUDY DESIGN: Gelatin hydrogels incorporating PRP, PRP-activated thrombin, or an empty gelatin hydrogel were applied to the defect, or the defect was left untreated. Bone regeneration was evaluated by microfocus computed tomography, peripheral quantitative computed tomography, and histological examinations. RESULTS: Successful bone regeneration was observed at the bone defect applied with the gelatin hydrogel incorporating PRP, which is in marked contrast to other groups. CONCLUSION: The gelatin hydrogel is a promising material capable of controlled release of platelet growth factors to enhance bone regeneration.     

Healing of an ulnar defect using a proprietary TCP bone graft substitute, JAX, in association with autologous osteogenic cells and growth factors

Currently, available synthetic bone substitutes have adequate osteoconductive properties but have little or no osteoinductivity. Recent research has focused on using osteogenic growth factors or cells to provide this. JAX is a beta tricalcium phosphate bone graft substitute that has a novel shape and interlocking design. This study investigated delivery methods and the use of autologous cell therapy to enhance healing of a bone defect using JAX as a scaffold. Bone marrow was harvested from 24 New Zealand White rabbits. The mononuclear cell fraction was isolated and culture expanded. Bilateral 1.5 cm defects in the ulna were filled with: Group 1: JAX alone, Group 2: JAX plus 1x10(7) autologous BMSCs injected at the time of surgery, Group 3: JAX plus 8x10(6) autologous BMSCs cultured on granules for 14 days prior to surgery, Group 4: JAX plus fresh bone marrow (BMA), Group 5: cortical autograft, Group 6: JAX plus 2.5 microg VEGF. Radiographs demonstrated that there was more new bone in the BMA and VEGF groups compared to JAX alone. Groups containing autologous BMSCs were only slightly better than JAX alone in the amount of bone in the defect but did improve bridging of the osteotomy. Histomorphometry identified a significant increase in bone volume in the BMA group compared to JAX alone. BMA and VEGF enhanced healing of bone defects whereas expanded BMSCs provided little advantage over scaffold alone. There was no difference between delivery methods of autologous BMSCs. These observations suggest that the provision of osteogenic cells alone is insufficient to enhance bone healing and that additional factors are required to initiate this process in vivo.     

Repair of mandible defect with tissue engineering bone in rabbits

BACKGROUND: The aim of the present study was to investigate the effect of tissue engineering bone composed of bone marrow-derived osteoblasts and demineralized bone in repairing mandible defect. METHODS: Bone marrow-derived osteoblasts of 20 rabbits were cultured and seeded into scaffold of allogeneic demineralized bone to construct tissue engineering bone graft in vitro, which was used to repair the 10 x 5-mm bone defect made in the same rabbit mandible edge. Implant of demineralized bone alone was as the control. Rabbits were killed according to the schedule: five after 2 weeks, five after 4 weeks, five after 8 weeks, five after 12 weeks, and the implants were harvested for gross, radiographic, and histological observation. RESULTS: New bone formation at the margin region of defect and osteogenesis at the centre were observed in the implant of tissue engineering bone, and the bone formation pattern included osteogenesis, osteoconduction, and osteoinduction. In the implant of demineralized bone alone, the major bone formation pattern was 'creeping substitute'. CONCLUSIONS: The tissue engineering bone graft constructed by autogenous bone marrow-derived osteoblasts and allogeneic demineralized bone was better than demineralized bone alone in bone formation capability, which might be an ideal graft for bone defect repair.     

Regulation of alloimmune responses (GvH reactions) in vitro by autologous donor bone marrow cell preparation used in clinical organ transplantation

BACKGROUND: Cadaver donor bone marrow cells (DBMC) are capable of a low-grade response to allogeneic stimulation in vitro, indicating their potential ability to cause graft versus host disease (GvHD). However, at this center, we have observed a lack of GvHD in kidney transplant recipients who received DBMC perioperatively. Therefore, we questioned whether an intrinsic immunoregulatory function of (subpopulations of) DBMC might play a role in this observation. METHODS: In in vitro assays, DBMC was added to autologous splenic responder cells taking part in allogeneic mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) reactions. RESULTS: When compared with autologous donor irradiated spleen cells as control modulators, DBMC significantly inhibited the CML, but to a much lesser extent than MLR, of autologous responding cells stimulated with allogeneic irradiated cells in a dose dependent manner. The down-regulation of CML responses was observed even in the presence of pharmacological concentrations FK506, mycophenolic acid, or cyclosporine-A. The inhibition could not be overcome by the addition of exogenous helper factors. Moreover, in contrast with findings previously reported from this laboratory of the in vitro inhibitory effect of DBMC on allogeneic responding cells in MLR and CML reactions to stimulating cells of the DBMC donor (allogeneic host versus graft inhibition), the following unique observations were made using DBMC inhibiting autologous reactions (GvH): (1) optimal restimulation of autologous responder cells in secondary cultures could not abrogate this inhibition; even activated responder cells could be inhibited by autologous DBMC, and (2) soluble factors were at least partially operative in this autologous (GvH) inhibition as indicated by experiments in transwells and by the CML inhibition caused by 50% supernatants from DBMC cultures. CONCLUSION: These in vitro results indicate that DBMC treatment brings about a marked down-regulation of autologous immunocompetent cells in cytotoxicity reactions, partially at least through secreted soluble factor(s), (and in presence of immunosuppressive drugs in vivo) thereby preventing overt clinical GvHD.     

Autologous platelet gel fails to show beneficial effects on wound healing after saphenectomy in CABG patients

Wound healing impairment in the leg after removal of the saphenous vein within the framework of a coronary artery bypass graft (CABG) operation represents a clinically significant problem. Patients suffer from this complication, and treatment of the wounds is costly in terms of both time and money. No method is known to date that reliably prevents postoperative wound healing disturbances. The effect of autologous platelet gel to stimulate wound healing is known from various medical disciplines. Within a prospective randomized study, we wanted to determine whether intraoperative use of autologous platelet gel on the leg during a CABG operation could reduce the incidence of postoperative wound healing disturbances. The application group (AG) included 35 patients and was compared to a control group (CG) that also had 35 patients. The platelet gel, as well as the thrombin required to activate the platelets, was prepared from autologous patient blood during the operation. Validation of the platelet gel comprised measurement of the growth factors platelet-derived growth factor AB (PDGF AB) and epidermal growth factor (EGF), as well as the thrombocyte and leukocyte counts. Wound healing was photographically documented after surgery, and the patients were contacted by telephone on day 50 after surgery to obtain information on wound healing status. After cell separation, the platelet count was 1616 +/- 845/microL, which is higher than in whole blood by a factor of 7.1 +/- 2.0, with a platelet yield of 47.0% +/- 13.2%. The PDGF AB concentration after activation of the platelets was raised by a median factor of 158 and EGF by a median factor of 64 compared with whole blood. During the primary clinical stay, no statistically significant differences were recorded in the number of hematomas, postoperative leg swelling, or pain level. Large-area hematomas were less frequent in the application group (AG, 29.4% vs. CG, 60%, p = .007). In the follow-up 51 +/- 9 days after surgery, 17.6% (6/34) of the patients from the AG and 31.4% (11/35) of the patients from the CG showed leg wound healing disturbances (p = .184). Using the cell separation system, a biological product that contains high concentrations of platelets, leukocytes, and growth factors can be prepared reproducibly. Despite optimum application of the autologous platelet gel to the wound, no clinically relevant differences were found between the groups, either during the primary clinic stay or in the follow-up period.     

Current applications of platelet gels in facial plastic surgery

The response of living tissue to injury is a central component in the planning of all surgical procedures. The wound-healing process is typically divided into three phases (inflammatory, proliferative, and remodeling) and is a complex process in which a multitude of cellular and humoral components interact to restore a wound defect. Platelets and their released cytokines and growth factors are pivotal in the modulation of this entire process. Although several techniques may be used to achieve hemostasis after initial injury, few initiate and actually accelerate tissue regeneration. Both platelet gel and fibrin glue are effective hemostatic agents. Platelet gels, unlike fibrin glue, have a high concentration of platelets that release the bioactive proteins and growth factors necessary to initiate and accelerate tissue repair and regeneration. In particular, two growth factors that play a major role in platelet gels are platelet-derived growth factor, a powerful chemoattractant, and transforming growth factor beta, which significantly increases and stimulates the deposition of extracellular matrix. In creating a platelet gel, autologous blood is centrifuged to produce a concentrate high in both platelets and plasma. This concentrate can be applied to wounds, providing hemostasis, adhesion, and enhanced wound healing. Recent techniques for the autologous concentrating process have been streamlined, and now platelet gels are clinically accessible to most physicians. Platelet gels have global applications in surgery and are especially useful for the soft tissue and bony reconstructions encountered in facial plastic and reconstructive surgery. In these applications, their use has been associated with a decrease in operative time, necessity for drains and pressure dressings, and incidence of complications. When applied to bony reconstruction it provides adhesion for the consolidation of cancellous bone and comminuted fracture segments.     

Bridging large defects in bone by demineralized bone matrix in the form of a powder. A radiographic, histological, and radioisotope-uptake study in rats

Demineralized bone powder was used as an osteoinductive substance to bridge very large defects (more than 50 per cent of the total length of the bone) in one radius of each of thirty-three rats. An identical defect was produced in the contralateral radius of each animal for use as a control. The defect on the control side was left unbridged or was bridged by large chips of autologous bone or an autologous inlay graft. All rats showed formation of new bone throughout the length of the radial defect only on the side in which the demineralized bone powder had been implanted. The control side, in which an autologous graft in the form of chips or inlay had been implanted, showed resorption of the graft. The maximum rate of formation of bone occurred fifteen to twenty-one days after implantation of the demineralized bone powder. At thirty-five days, the experimental defect was fully bridged, forming solid bone, in 71 per cent of the rats, and the remaining 29 per cent showed bridging of 95.8 per cent of the length of the defect, with union on one side. Analysis of the sequential radiographs, technetium-99m scans, and histological findings showed that the formation of bone and bridging of the defect were superior on the side in which the demineralized bone powder had been implanted compared with the side in which pieces of autologous bone or an autologous inlay graft had been used.(ABSTRACT TRUNCATED AT 250 WORDS)     

Osteogenetic activity in composite grafts of demineralized compact bone and marrow

The effects of a composite graft of autologous marrow and demineralized autologous compact bone on the healing of a surgically created bone defect were observed in adult rabbits. A segment of the radius was bilaterally resected, demineralized, and replaced. On one side the bone graft was supplemented with autologous marrow. The new bone formation was measured 14 and 28 days after operation by roentgenography, including planimetry with scintigraphy and autoradiography using 99mTc-labelled MDP. The composite graft, i.e., demineralized compact bone and marrow, had a significantly higher (p less than 0.01) bone formation rate 14 days after operation compared with the graft with demineralized compact bone in the opposite radius. At 28 days, however, there were no differences between the sides. Viable autologous marrow cells and demineralized autologous compact bone graft accelerate the rate of osteogenesis, but only at the beginning of the healing process.     

自体骨修复初次全膝关节置换术中胫骨骨缺损的临床研究

目的为了探讨初次全膝关节置换术中自体骨修复胫骨平台骨缺损患者植骨处的骨密度变化及骨愈合情况,对自体骨修复胫骨平台骨缺损患者的随访探讨。方法收集2008年6月至2010年3月,在15例（16膝）初次全膝关节置换术中,采用自体骨移植的方法修复胫骨平台骨缺损的患者。对照组收集同期的14例（16膝）无骨缺损患者。应用X线拍片及双能X线骨密度仪（DEXA）观察术后6个月、12个月时胫骨假体下骨密度。分为3个兴趣区（ROI）,对各个区内平均骨密度变化进行观察和分析。结果术后6个月时胫骨平台骨缺损处ROI的骨密度：（0.967±0.320）g/cm2,对照组ROI的骨密度：（0.946±0.263）g/cm2;术后12个月时胫骨平台骨缺损处ROI的骨密度：（0.808±0.258）g/cm2,对照组ROI的骨密度：（0.806±0.262）g/cm2。术后12个月时胫骨平台骨缺损植骨处平均骨密度较6个月时均数略有下降,但无统计学差异（P〉0.05）;术后6个月与12个月时胫骨平台骨缺损自体骨植骨处平均骨密度较无骨缺损患者ROI的骨密度无显著性差异（P〉0.05）。结论自体骨修复胫骨平台骨缺损的全膝关节置换术后患者植骨处骨密度较无骨缺损患者的骨密度无明显变化,骨愈合情况良好。     

Cranioplasty using autologous calvarial bone graft in combination with titanium mesh plates for patients with a history of bone infections after initial cranioplasty

We present a modified method for reconstruction of calvarial bone defects for patients with a history of infectious complications. Three patients who had experienced implanted bone infections underwent reconstruction of calvarial bone defect. For reconstruction of the calvarial bone defects, autologous split calvarial bone grafts were used to cover the calvarial bone defect. The full or half layered fronto-parietal bone used as implants were fixed with titanium mini-plates for primary bone defect site, while the new bone defect site caused by getting autologous bone graft were covered with titanium mesh plates assisted by residual half layered calvarias. The average follow-up span of patients was 64 months. Evaluated clinical and radiologic results are stable, showing no measurable side effects. Split calvarial bone graft in combination with titanium mesh plates is recommended in patients with a history of infection or high risk of infection.     

The influence of hydroxyapatite granules on the healing of a segmental defect filled with autologous bone marrow.

Hydroxyapatite(HA) ceramics are frequently used as a bone graft substitutes for the filling of bony defects. The addition of autologous bone marrow to HA ceramics does improve defect healing. There is conflicting evidence in the literature whether autologous bone marrow transplantation alone is as effective as the combination of HA ceramics and bone marrow combined. It was the purpose of this study to identify the role of additional HA ceramic granules on the healing of a sheep tibia segmental defect filled with autologous bone marrow. After permission of the local animal rights committee was obtained, a 3 cm segmental defect in the midshaft of 31 adult sheep was stabilized with an unreamed tibia nail. The animals were divided into 4 groups according to the mode of defect filling: HA plus autologous bone marrow (HA + MAR) (n = 8), autologous bone marrow (MAR) (n = 9), empty defect (DEF) (n = 6), cancellous bone graft (CAN) (n = 8). After three months follow up animals were sacrificed and analysed for the key parameters of union and maximum torque at failure. One nonunion was present in each of the HA + MAR, MAR, and CAN groups. Four of the six animals in the DEF group developed a nonunion. Maximum torque at failure was reported as percentage of the intact contralateral tibia: HA + MAR 39% +/- 24%, MAR 26% +/- 17%, DEF 22% +/- 13%, CAN 41% +/- 20%. The difference between the groups was statistically significant, but appeared to be relevant. We conclude from our data, that HA ceramics do improve healing of a segmental defect in the sheep tibia filled with autologous bone marrow. The results of this combination are comparable to cancellous autograft.     

Growth factors in bone repair

The role of growth factors (GF) in bone repair is widely recognised, particularly for bone morphogenetic proteins (BMPs), fibroblast growth factor (FGF), insulin-like growth factors (IGFs), platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF). GF are usually stored in the extracellular matrix (ECM), but after injury are actively released by ECM, cells and platelets. In this paper, the use of different recombinant GF for bone repair stimulation is summarised in experimental research and clinical applications. Drug delivery systems, including carriers, cell or gene therapy, are needed to ensure a sustained local release of the factors, but efficacy and potential side effects of such systems require additional research prior to clinical applications. Current sources for delivery of a GF mixture into the site of bone repair are platelet gel and demineralised bone matrix. Nevertheless, the levels of GF in such preparations are affected by variability among donors and differences in preparation. Autogenous GF, produced by the patient himself during the bone repair process, potentially interfere with prosthetic devices or even have a role in implant loosening due to the periprosthetic tissue reaction. In conclusion, GF are key components of functional bone regeneration: screening of basic research results and controlled clinical trials are accelerating the development of GF in orthopaedic surgery.