Objectives. Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. Methods. Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays. Results. After six weeks, the area of mineralisation was significantly higher for the transplanted osteophytes than for the cancellous bone (43803 μm. 2. , . sd. 14660 versus 9421 μm. 2. , . sd. 5032, p = 0.0184, one-way analysis of variance). Compared with cancellous bone, the conditioned medium prepared using osteophytes contained a significantly higher amounts of transforming growth factor (TGF)-β1 (471 pg/ml versus 333 pg/ml, p = 0.0001, Wilcoxon rank sum test), bone morphogenetic protein (BMP)-2 (47.75 pg/ml versus 32 pg/ml, p = 0.0214, Wilcoxon rank sum test) and insulin-like growth factor (IGF)-1 (314.5 pg/ml versus 191 pg/ml, p = 0.0418, Wilcoxon rank sum test). The stronger effects of osteophytes towards osteoblasts in terms of a higher proliferation rate, upregulation of gene expression of differentiation markers such as alpha-1 type-1 collagen and alkaline phosphate, and higher migration, compared with cancellous bone, was confirmed. Conclusion. We provide evidence of favourable features of osteophytes for bone mineralisation through a direct effect on osteoblasts. The acceleration in metabolic activity of the osteophyte provides justification for future studies evaluating the clinical use of osteophytes as autologous bone grafts. Cite this article: K. Ishihara, K. Okazaki, T. Akiyama, Y. Akasaki, Y. Nakashima. Characterisation of osteophytes as an autologous bone graft source: An experimental study in vivo and in vitro. Bone Joint Res 2017;6:73–81. DOI: 10.1302/2046-3758.62.BJR-2016-0199.R1

Introduction. AlloStem/Cellular Bone Allograft and autologous bone graft are accepted methods for managing hindfoot degenerative arthritis. The purpose was to evaluate outcomes of AlloStem and autograft in subtalar arthrodesis and compare overall fusion rates. Methods. This study was conducted in IRB compliance. Patients between 18–80 years who qualified for a subtalar fusion were randomized 1:1 to AlloStem or autologous graft. The AOFAS hindfoot ankle scale, FFI-R and SF-12 were collected pre-operatively, 6 weeks, 3 & 6 months, 1 and 2 year. Weight-bearing 3-view ankle X-rays were done at the same intervals. A CT scan was obtained at 6 months. Results. 140 patients were enrolled; 124 patients had surgery(60-AlloStem and 64-Control). Withdrawals included 14 voluntarily before surgery and 2 intra-operative failures. 19 were lost to follow-up. Mean age for AlloStem was 56.69(20.3–79.6) and Autograft was 54.60(20.74–80.07). 59 AlloStem patients completed their 6 month visit and 45 completed 2 years. AOFAS score improved: 40.02 at pre-op to 72.16(6 mo) to 79.51 at 1 year and 80.38 at 2 year. SF-12 improved 58.29 at pre-op to 65.67 at 6 month and 71.59 at 2 year. FFI-R improved 236.88 at pre-op to 203.53 at 6 month 149.93 at 2 year.60 Autograft patients completed their 6 month visit and 51 patients completed their 2 year. AOFAS score improved 42.89 at pre-op to 75.67 (6 mo) to 79.75 at 1 year and 78.62 at 2 year. Autograft SF-12 improved 60.55 at pre-op to 70.40 at 6 month and 75.26 at 2 year. Autograft FFI-R improved 217.16 at pre-op to 166.77 at 6 month and 145.43 at 2 year. AlloStem patients had a mean posterior fusion rate of 28.9% at 6 months whereas the Autograft had 46.3%(p=.049). Non-union rates were AlloStem(9/57)(15.7%) whereas Autograft was 3/60(5%). Conclusion. AlloStem trended to be inferior to Autologous graft

We reviewed, retrospectively, 13 patients who had undergone open anterograde autologous bone grafting of the talus for symptomatic osteochondral defects of the dome of the talus. The mean age of the seven men and six women was 38.4 years. The defects included the full thickness of articular cartilage, extended through the subchondral plate and were associated with subchondral cysts. Six patients (46%) were clinical failures requiring further surgery. Of the remaining seven, functional outcome results were obtained at a mean of 51.9 months after surgery. The mean outcome scores for the Musculoskeletal Outcomes Data Evaluation and Management System foot and ankle questionnaire and the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale were 87.0 and 84.3, respectively. There was an overall 46.2% patient satisfaction rate. We believe that the technique of autologous bone grafting presented should be used with extreme caution, when considered as the primary treatment for the adult patient with a symptomatic advanced osteochondral defect of the talus

Aims. Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures. Methods. A structured search of MEDLINE, EMBASE, the online archives of Bone & Joint Publishing, and CENTRAL databases from inception until 28 July 2021 was performed. Randomized, controlled, clinical trials that compared autologous and synthetic bone grafts in tibial plateau fractures were included. Preclinical studies, clinical studies in paediatric patients, pathological fractures, fracture nonunion, or chondral defects were excluded. Outcome data were assessed using the Risk of Bias 2 (ROB2) framework and synthesized in random-effect meta-analysis. The Preferred Reported Items for Systematic Review and Meta-Analyses guidance was followed throughout. Results. Six studies involving 353 fractures were identified from 3,078 records. Following ROB2 assessment, five studies (representing 338 fractures) were appropriate for meta-analysis. Primary outcomes showed non-significant reductions in articular depression at immediate postoperative (mean difference -0.45 mm, p = 0.25, 95%confidence interval (CI) -1.21 to 0.31, I. 2. = 0%) and long-term (> six months, standard mean difference -0.56, p = 0.09, 95% CI -1.20 to 0.08, I. 2. = 73%) follow-up in synthetic bone grafts. Secondary outcomes included mechanical alignment, limb functionality, and defect site pain at long-term follow-up, perioperative blood loss, duration of surgery, occurrence of surgical site infections, and secondary surgery. Mean blood loss was lower (90.08 ml, p < 0.001, 95% CI 41.49 to 138.67) and surgery was shorter (16.17 minutes, p = 0.04, 95% CI 0.39 to 31.94) in synthetic treatment groups. All other secondary measures were statistically comparable. Conclusion. All studies reported similar methodologies and patient populations; however, imprecision may have arisen through performance variation. These findings supersede previous literature and indicate that, despite perceived biological advantages, autologous bone grafting does not demonstrate superiority to synthetic grafts. When selecting a void filler, surgeons should consider patient comorbidity, environmental and societal factors in provision, and perioperative and postoperative care provision. Cite this article: Bone Jt Open 2022;3(3):218–228

Objectives. Fracture non-union poses a significant challenge to treating orthopaedic surgeons. These patients often require multiple surgical procedures. The incidence of complications after Autologous Bone Graft (ABG) harvesting has been reported up to 44%. These complications include persistent severe donor site pain, infection, heterotopic ossification and antalgic gait. We retrospectively compared the use of BMP-7 alone in long bone fracture Non-union, with patients in whom BMP-7 was used in combination with the Autologous Bone Graft (ABG). Material and Methods. The databases of our dedicated Limb Reconstruction Unit were searched for patient with three common long bone fractures Non-unions (Tibia, Femur and Humerus). The patients who had intra-operative use of Bone Morphogenetic Protein (BMP-7) alone and in combination with ABG were evaluated. 53 Patients had combined use of ABG and BMP-7, and 65 patients had BMP-7 alone. Results. In the ABG and BMP-7 group, the union rate for femoral (n=18) Non-unions was 83%, for humeral (n=16) Non-unions 81%, and for tibia (n=19) Non-unions it was 47%. In the BMP-7 alone group, 83% of the femoral (n=12) Non-unions, 87% of the humeral (n=16) and 56% of the tibial (n=37) Non-unions healed. The common risk factors for Non-union were comparable in both the groups and included location and nature (open vs closed) of fracture, infection, smoking and NSAIDs use. The average time to union in ABG+BMP-7 group was 8.1 months (range 3-30 months) and in BMP-7 alone group it was 7.2 months (range 3-24 months). Conclusion. Autologous Bone Grafting has a pivotal role in limb reconstruction surgery but its indication should be carefully evaluated in view of considerable morbidity associated with graft donor site. Our study did not show any significant difference in the union rates of common long bone fracture Non-unions treated with BMP-7 alone or with a combination of Autologous Bone Graft and BMP-7

The aim of this paper is to describe the technique and evaluate the effectiveness of the RIA system in the first cases of bone loss treated by the authors with this technique.

Between January 2010 and January 2011, ten patients were treated with an average age of fourty six years, with infected bone loss as a result of open fractures in various bone segments, with multiple failed treatment attempts, including three humeri, four femurs and three tibiae. The average size of the initial bone loss was 4 cm, varying from 1 to 8 cm. In 4 patients it was used simultaneously a Ilizarov apparatus with acute compression of the focus, in two patients a Ender pin and monolateral external fixator, three other cases with a SAFE nail with core with antibiotics and in one case an osteosynthesis with a plate and screws. The RIA was introduced with a percutaneous technique with a one pass drilling. The graft thus collected was mixed with appropriate antibiotics and aplied at the defect. The volume of the harvested graft, complications of the donor and recipient and the final results was recorded.

The review showed that the average volume of graft was 60 cc, from 20 to 90 cc. In two female patients older than 70 years with osteoporosis, insufficient bone of poor quality was obtained. Problems included a case of iatrogenic fracture of the donor site, due to poor surgical technique and a case of relapse of the nonunion. Regarding the effectiveness of grafts extracted with the RIA system, 90% of the cases achieved consolidation in average of 5 months after grafting, range 3–9 months.

This short experience with the RIA system showed that it is an attractive method allowing a rapid removal of a large volume of bone graft with a minimally invasive approach and a short learning curve. It is not indicated in elderly patients with osteoporosis and those with a narrow medullar canal less than 11 mm. Special attention must be done to the need to choose a drill no larger than 1 mm of the diameter of the isthmus, to do a single entry point and with only one drill passage to prevent the weakening of the donor site.

Purpose

The aim of this study was to report the outcomes of a series of patients with clavicle fracture non-union who had undergone open reduction and internal fixation using a contoured locking plate without the use of distant bone graft.

A study to evaluate the efficacy of combined grafting (iliac crest autograft – ICAG, and human recombinant osteogenic protein 1 – rhOP1/BMP7) for long bone fracture non-unions (LBFNUs).

At both institutions prospective and retrospective data were collected. (Between Oct 2001 and Aug 2004 all LBFNUs that were grafted with a combination of BMP7 and ICAG). The records of the initial injury incident, treatment course, all operative interventions before and after the combined grafting and the follow up till final clinical & radiological union have been analysed. X2 test was used to analyse the results.

Forty-nine patients (31 males) with a mean age of 43 years (18–79) with LBFNUs were identified. The mean follow-up was 21.4 months (12–65). 7 were humeral, 13 femoral, and 29 tibial LBFNUs. Eleven were open (3 grade II, 8 grade IIIa–b). All non-unions were atrophic, and 8 had significant bone defects. The mean number of operations prior to the combined grafting was 2.5 (0–6). Clinical and Radiological union occurred within a mean time of 4.4 (3–12) months and 5.4 (4–16) months respectively. All of the fractures united. One patient, with an infected tibial non-union after an open fracture, ultimately underwent a below knee amputation. No complications or adverse effects from the use of BMP-7 were encountered.

BMP-7 was used as a bone-stimulating agent combined with conventional iliac crest bone grafting with a success rate of 98% in this series of patients with LBFNUs. This study supports the view that this combination of BMP-7 is safe and a power adjunct to be considered in the surgeon’s armamentarium for the management of such difficult cases.

Purpose: The purpose of this study was to evaluate the efficacy of a combined application of iliac crest autograft (ICAG) and human recombinant osteogenic protein 1 (BMP-7) for the treatment of non-unions of long bones fractures (LBF).

Patients and Methods: At both institutions we have prospectively and retrospectively collected and analysed data of patients admitted between October 2001 and August 2004 with a LBF nonunion (humerus, femur, tibia) and whose nonunion sites have been grafted with a combination of BMP7 and ICAG. All the records of the patients’ initial injury incident and treatment course, together with following operative interventions till and after the BMP7 application, and their follow up till final union have been analysed. Painless full weight bearing or use of the upper limp in the case of humerus (clinical union), and presence of bridging callous of two cortices visible on two x-ray views (radiological union). Chi square test was used to analyse the results.

Results: Forty-nine patients (31 males) with a mean age of 43 years (18–79) with LBF non-unions were identified. The mean follow-up was 21.4 months (range 12–65). 7 were humerus, 13 femurs, and 29 tibias. Eleven cases were open (3 grade II, and 8 grade IIIa-b). All non-unions were atrophic, and 8 were initially associated with bone loss. The mean number of operations performed prior to the combined ICAG and BMP7 application was 2.5 (0–6), including ICAG in 12 cases and bone marrow injection in 1 case. All but one of the fractures have united. Clinical and Radiological union occurred within a mean time of 4.4 (3–12) months and 5.4 (4–16) months respectively. One patient, with an infected tibial non-union following an open fracture, ultimately underwent a below knee amputation, secondary to recurrence of deep sepsis. The only patient whose (tibial) fracture has not still united is currently on an Ilizarov frame and slow progression has been reported following a recent CT. No complications or adverse effects from the use of BMP-7 were encountered.

Conclusion: BMP-7 was used as a bone stimulating agent combined with conventional iliac crest bone grafting with a success rate of 98% in this series of patients with LBF non-unions. This study supports the view that this combination of BMP-7 is safe and a power adjunct to be considered in the surgeon’s armamentarium for the management of such difficult cases.

Tibial grafts in rabbits were studied using a microscopic technique in vivo that made it possible to photograph the "graft to be" at the donor site and then subsequently to observe the same graft repeatedly at the host site. With this method the effects on the graft tissues of varying degrees of surgical trauma have been tested. The period of follow-up ranged between 14 and 300 days. The grafts removed with minimal trauma showed a more rapid rapid of revascularisation. In this group the first vessels appeared on average seven days after grafting, whereas they took 15 days in the grafts which were more severely traumatised. Bone remodelling started when the vascular density resembled the more pattern and this occurred earlier and much more rapidly in the minimally injured grafts. It correlated with the presence of surviving cells, as shown by histochemical tests, and a causal relationship is suggested. It is concluded that control of trauma is important not only in the preparation of the host bed but also in procurement of the graft. Suggestions are given on techniques to minimise the surgical trauma.

Autologous cancellous bone graft is the gold standard in large bone defect repair. However, studies using autologous bone grafting in rats are rare and donor sites as well as harvesting techniques vary. The aim of this study was to determine the feasibility of autologous cancellous bone graft harvest from 5 different anatomical sites in rats and compare their suitability as donor sites for autologous bone graft. 13 freshly euthanised rats were used to describe the surgical approaches for autologous bone graft harvest from the humerus, iliac crest, femur, tibia and tail vertebrae (n=4), determine the cancellous bone volume and microstructure of those five donor sites using µCT (n=5), and compare their cancellous bone collected qualitatively by looking at cell outgrowth and osteogenic differentiation using an ALP assay and Alizarin Red S staining (n=4). It was feasible to harvest cancellous bone graft from all 5 anatomical sites with the humerus and tail being more surgically challenging. The microstructural analysis showed a significantly lower bone volume fraction, bone mineral density, and trabecular thickness of the humerus and iliac crest compared to the femur, tibia, and tail vertebrae. The harvested volume did not differ between the donor sites. All donor sites apart from the femur yielded primary osteogenic cells confirmed by the presence of ALP and Alizarin Red S stain. Bone samples from the iliac crest showed the most consistent outgrowth of osteoprogenitor cells. The tibia and iliac crest may be the most favourable donor sites considering the surgical approach. However, due to the differences in microstructure of the cancellous bone and the consistency of outgrowth of osteoprogenitor cells, the donor sites may have different healing properties, that need further investigation in an in vivo study

Aims. Various surgical techniques have been described for total hip arthroplasty (THA) in patients with Crowe type III dislocated hips, who have a large acetabular bone defect. The aim of this study was to evaluate the long-term clinical results of patients in whom anatomical reconstruction of the acetabulum was performed using a cemented acetabular component and autologous bone graft from the femoral neck. Methods. A total of 22 patients with Crowe type III dislocated hips underwent 28 THAs using bone graft from the femoral neck between 1979 and 2000. A Charnley cemented acetabular component was placed at the level of the true acetabulum after preparation with bone grafting. All patients were female with a mean age at the time of surgery of 54 years (35 to 68). A total of 18 patients (21 THAs) were followed for a mean of 27.2 years (20 to 33) after the operation. Results. Radiographs immediately after surgery showed a mean vertical distance from the centre of the hip to the teardrop line of 21.5 mm (SD 3.3; 14.5 to 30.7) and a mean cover of the acetabular component by bone graft of 46% (SD 6%; 32% to 60%). All bone grafts united without collapse, and only three acetabular components loosened. The rate of survival of the acetabular component with mechanical loosening or revision as the endpoint was 86.4% at 25 years after surgery. Conclusion. The technique of using autologous bone graft from the femoral neck and placing a cemented acetabular component in the true acetabulum can provide good long-term outcomes in patients with Crowe type III dislocated hips. Cite this article: Bone Joint J 2021;103-B(2):299–304

Polyetheretherketone (PEEK) interbody fusion cages combined with autologous bone graft is the current clinical gold standard treatment for spinal fusion, however, bone graft harvest increases surgical time, risk of infection and chronic pain. We describe novel low-stiffness 3D Printed titanium interbody cages without autologous bone graft and assessed their biological performance in a pre-clinical in vivo interbody fusion model in comparison to the gold standard, PEEK with graft. Titanium interbody spacers were 3D Printed with a microporous (Ti1: <1000μm) and macroporous (Ti2: >1000μm) design. Both Ti1 and Ti2 had an identical elastic modulus (stiffness), and were similar to the elastic modulus of PEEK. Interbody fusion was performed on L2-L3 and L4-L5 vertebral levels in 24 skeletally mature sheep using Ti1 or Ti2 spacers, or a PEEK spacer filled with iliac crest autograft, and assessed at 8 and 16 weeks. We quantitatively assessed bone fusion, bone area, mineral apposition rate and bone formation rate. Functional spinal units were biomechanically tested to analyse range of motion, neutral zone, and stiffness. Results: Bone formation in macroporous Ti2 was significantly greater than microporous Ti1 treatments (p=.006). Fusion scores for Ti2 and PEEK demonstrated greater rates of bone formation from 8 to 16 weeks, with bridging rates of 100% for Ti2 at 16 weeks compared to just 88% for PEEK and 50% for Ti1. Biomechanical outcomes significantly improved at 16 versus 8 weeks, with no significant differences between Ti and PEEK with graft. This study demonstrated that macroporous 3D Printed Ti spacers are able to achieve fixation and arthrodesis with complete bone fusion by 16 weeks without the need for bone graft. These significant data indicate that low-modulus 3D Printed titanium interbody cages have similar performance to autograft-filled PEEK, and could be reliably used in spinal fusion avoiding the complications of bone graft harvesting

Aims. We present our experience of using a metal-backed prosthesis and autologous bone graft to treat gross glenoid bone deficiency. Patients and Methods. A prospective cohort study of the first 45 shoulder arthroplasties using the SMR Axioma Trabecular Titanium (TT) metal-backed glenoid with autologous bone graft. Between May 2013 and December 2014, 45 shoulder arthroplasties were carried out in 44 patients with a mean age of 64 years (35 to 89). The indications were 23 complex primary arthroplasties, 12 to revise a hemiarthroplasty or resurfacing, five for aseptic loosening of the glenoid, and five for infection. Results. Of the 45 patients, 16 had anatomical shoulder arthroplasties (ASA) and 29 had reverse shoulder arthroplasties (RSA). Postoperatively, 43/45 patients had a CT scan. In 41 of 43 patients (95%), the glenoid peg achieved > 50% integration. In 40 of 43 cases (93%), the graft was fully or partially integrated. There were seven revisions (16%) but only four (9%) required a change of baseplate. Four (25%) of the 16 ASAs were revised for instability or cuff failure. At two-year radiological follow-up, five of the 41 cases (11%) showed some evidence of lucent lines. Conclusion. The use of a metal baseplate with a trabecular titanium surface in conjunction with autologous bone graft is a reliable method of addressing glenoid bone defects in primary and revision RSA setting in the short term. ASAs have a higher rate of complications with this technique

Treatment of large bone defects represents a great challenge for orthopedic surgeons. The main causes are congenital abnormalities, traumas, osteomyelitis and bone resection due to cancer. Each surgical method for bone reconstruction leads its own burden of complications. The gold standard is considered the autologous bone graft, either of cancellous or cortical origin, but due to graft resorption and a limitation for large defect, allograft techniques have been identified. In the bone defect, these include the placement of cadaver bone or cement spacer to create the ‘Biological Chamber’ to restore bone regeneration, according to the Masquelet technique. We report eight patients, with large bone defect (for various etiologies and with an average size defect of 13.3 cm) in the lower and upper limbs, who underwent surgery at our Traumatology Department, between January 2019 and October 2020. Three patients were treated with both cortical and cancellous autologous bone grafts, while five received cortical or cement spacer allografts from donors. They underwent pre and postoperative radiographs and complete osseointegration was observed in all patients already undergoing monthly radiographic checks, with a restoration of length and range of motion. In our study, both the two stage-Masquelet and the cortical bone graft from a cadaver donor proved to be valid techniques in patients with very extensive defects to reconstruct the defect, restore the length, minimize implant left in situ and achieve complete functional recovery

Medial opening wedge high tibial osteotomy (MOWHTO) is the workhorse procedure for correcting varus malalignment of the knee. There have been recent developments in the synthetic options to fill the osteotomy gap. The current gold standard for filling this osteotomy gap is autologous bone graft which is associated with donor site morbidity. We would like to introduce and describe the process of utilizing the novel Osteopore® 3D printed, honeycomb structured, Polycaprolactone and β-Tricalcium Phosphate wedge for filling the gap in MOWHTO. In the advent of additive manufacturing and the quest for more biocompatible materials, the usage of the Osteopore® bone wedge in MOWHTO is a promising technique that may improve the biomechanical stability as well the healing of the osteotomy gap

Critical-sized bone defects remain challenging in the clinical setting. Autologous bone grafting remains preferred by clinicians. However, the use of autologous tissue is associated with donor-site morbidity and limited accessibility to the graft tissue. Advances in the development of synthetic bone substitutes focus on improving their osteoinductive properties. Whereas osteoinductivity has been demonstrated with ceramics, it is still a challenge in case of polymeric composites. One of the approaches to improve the regenerative properties of biomaterials, without changing their synthetic character, is the addition of inorganic ions with known osteogenic and angiogenic properties. We have previously reported that the use of a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50% beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating of the TCP particles can enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) (3). To further support the regenerative properties of these scaffolds, inorganic ions with known angiogenic properties, copper or cobalt, were added to the coating solution. β-TCP particles were immersed in a zinc and copper or zinc and cobalt solution with a concentration of 15 or 45 mM. 3D porous scaffolds composed of 1000PEOT70PBT30 and pure or coated β-TCP were additively manufactured by 3D fibre deposition. The osteogenic and angiogenic properties of the fabricated scaffolds were tested in vitro through culture with hMSCs and human umbilical vein endothelial cells, respectively. The materials were further evaluated through ectopic implantation in an in vivo mini-pig model. The early expression of relevant osteogenic gene markers (collagen-1, osteocalcin) of hMSCs was upregulated in the presence of lower concentration of inorganic ions. Further analysis will focus on the evaluation of ectopic bone formation and vascularisation of these scaffolds after implantation in a mini-pig ectopic intramuscular model

Aim. The number of operatively treated clavicle fractures has increased over the past decades. Consequently, this has led to an increase in secondary procedures required to treat complications such as fracture-related infection (FRI). The primary objective of this study was to assess the clinical and functional outcome of patients treated for FRI of the clavicle. The secondary objectives were to evaluate the healthcare costs and propose a standardized protocol for the surgical management of this complication. Method. All patients with a clavicle fracture who underwent open reduction and internal fixation (ORIF) between 1 January 2015 and 1 March 2022 were retrospectively evaluated. This study included patients with an FRI who were diagnosed and treated according to the recommendations of a multidisciplinary team at the University Hospitals Leuven, Belgium. Results. We evaluated 626 patients with 630 clavicle fractures who underwent ORIF. In total, 28 patients were diagnosed with an FRI. Of these, eight (29%) underwent definitive implant removal, five (18%) underwent debridement, antimicrobial treatment and implant retention, and fourteen patients (50%) had their implant exchanged in either a single-stage procedure, a two-stage procedure or after multiple revisions. One patient (3.6%) underwent resection of the clavicle. Twelve patients (43%) underwent autologous bone grafting (tricortical iliac crest bone graft (n=6), free vascularized fibular graft (n=5), cancellous bone graft (n=1)) to reconstruct the bone defect. The median follow-up was 32.3 (P. 25. -P. 75. : 23.9–51.1) months. Two patients (7.1%) experienced a recurrence of infection. The functional outcome was satisfactory, with 26 out of 28 patients (93%) having full range of motion. The median healthcare cost was € 11.506 (P. 25. -P. 75. : € 7.953–23.798) per patient. Conclusion. FRI is a serious complication that can occur after the surgical treatment of clavicle fractures. Overall, the outcome of patients treated for FRI of the clavicle is good, when management of this complication is performed by using a multidisciplinary team approach. The median healthcare costs of these patients are up to 3.5 times higher compared to non-infected operatively treated clavicle fractures. Expert opinion considers factors such as the size of the bone defect, the condition of the soft tissue, and patient demand to guide surgical decision making

Bone morphogenetic proteins (BMPs) have been widely investigated for treating non-healing fractures. They participate in bone reconstruction by inducing osteoblast differentiation, and osteoid matrix production. 1. The human recombinant protein of BMP-7 was among the first growth factors approved for clinical use. Despite achieving comparable results to autologous bone grafting, severe side effects have been associated with its use. 2. Furthermore, BMP-7 was removed from the market. 3. These complications are related to the high doses used (1.5-40 miligrams per surgery). 2. compared to the physiological concentration of BMP in fracture healing (in the nanogram to picogram per milliliter range). 4. In this study, we use transcript therapy to deliver chemically modified mRNA (cmRNA) encoding BMP-7. Compared to direct use of proteins, transcript therapy allows the sustained synthesis of proteins with native conformation and true post-translational modifications using doses comparable to the physiological ones. 5. Moreover, cmRNA technology overcomes the safety and affordability limitations of standard gene therapy i.e. pDNA. 6. BMP-7 cmRNA was delivered using Lipofectamine™ MessengerMAX™ to human mesenchymal stromal cells (hMSCs). We assessed protein expression and osteogenic capacity of hMSCs in monolayer culture and in a house-made, collagen hydroxyapatite scaffold. Using fluorescently-labelled cmRNA we observed an even distribution after loading complexes into the scaffold and a complete release after 3 days. For both monolayer and 3D culture, BMP-7 production peaked at 24 hours post-transfection, however cells transfected in scaffolds showed a sustained expression. BMP-7 transfected hMSCs yielded significantly higher ALP activity and Alizarin red staining at later timepoints compared to the untransfected group. Interestingly, BMP-7 cmRNA treatment triggered expression of osteogenic genes like OSX, RUNX-2 and OPN, which was also reflected in immunostainings. This work highlights the relevance of cmRNA technology that may overcome the shortcomings of protein delivery while circumventing issues of traditional pDNA-based gene therapy for bone regeneration. Acknowledgement: This work has been performed as part of the cmRNAbone project and has received funding from the European Union's Horizon 2020 research and innovation programme under the Grant Agreement No 874790