Aims

Autologous bone graft (ABG) is considered the ‘gold standard’ among graft materials for bone regeneration. However, complications including limited availability, donor site morbidity, and deterioration of regenerative capacity over time have been reported. P-15 is a synthetic peptide that mimics the cell binding domain of Type-I collagen. This peptide stimulates new bone formation by enhancing osteogenic cell attachment, proliferation, and differentiation. The objective of this study was to conduct a systematic literature review to determine the clinical efficacy and safety of P-15 peptide in bone regeneration throughout the skeletal system.

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment. Cite this article: Bone Joint Res 2024;13(12):725–740

Aims. This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis. Methods. We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed. Results. In total, 314 patients with a mean age of 52.1 years (SD 12.1) were enrolled. After a mean of 50 months’ (24 to 96) follow-up, 53 (16.9%) patients had infection recurrence including 32 tibiae, ten femora, ten calcanea, and one humerus. Of all patients with recurrence, 30 (9.6%) occurred within one year and 39 (12.4%) within two years. Among them, 41 patients needed reoperation, five received antibiotics treatment only, and seven ultimately required amputations. Following multivariable analysis, we found that patients infected with Gram-negative bacilli were more likely to have a recurrence (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.20 to 6.94; p = 0.046) compared to Staphylococcus aureus; segmental bone defects (OR 5.25, 95% CI 1.80 to 15.26; p = 0.002) and smoking (OR 3.00, 95% CI 1.39 to 6.50; p = 0.005) were also independent risk factors for recurrence after treatment. Conclusion. Permanent ALCS might be an alternative strategy for definitive bone defect management in selected osteomyelitis cases. However, the overall high recurrence found suggests that it should be cautiously treated. Additionally, segmental defects, Gram-negative infections, and smoking were associated with an increased risk of infection recurrence. Cite this article: Bone Joint Res 2023;12(8):467–475

Aim. The aim of this systematic review was to determine the reported treatment strategies, their individual success rates, and other outcome parameters in the management of critical-sized bone defects in Fracture-Related Infection (FRI) patients between 1990 and 2018. Method. We performed a systematic literature search on treatment and outcome of critical-sized bone defects in FRI. Treatment strategies identified were, autologous cancellous grafts, autologous cancellous grafts combined with local antibiotics, the induced membrane technique, vascularized grafts, bone transport, and bone transport combined with local antibiotics. Studies describing bone defects of 1 cm or greater were included. Outcomes were bone healing and infection eradication after primary surgical protocol and recurrence of FRI and amputations at the end of study period. Results. Fifty studies were included, describing 1,530 patients, of which the tibia was affected in 82%. The mean age was 40 years (range 6–80), with predominantly male subjects (79%). Mean duration of infection was 17 months (range 1–624) and mean follow-up lasted 51 months (range 6–126). Four studies (8%) described treatment using vascularized grafts, 18 (36%) cancellous grafts, 8 (16%) the induced membrane technique, and 20 (40%) bone transport. A total of 1063 grafts were used of which 30% were vascularized and 60% were cancellous bone. After initial protocolized treatment, FRI was cured in 83% (95% CI 79–87) of all cases, increasing to 94% (95% CI 92–96) at the end of each individual study. Recurrence of infection was seen in 8% (95% CI 6–11) and amputation in 3% (95% CI 2–3). Conclusions. This is the first extensive review of bone defect treatment protocols in chronic/late-onset FRI. Overall published work showed a high success rate of 94% and low amputation rate of only 3%. However, data did not allow a reliable comparison across treatments. The results should thus be interpreted with caution due to the retrospective and observational design of most studies, the lack of clear classification systems, incomplete data reports, potential underreporting of adverse outcomes, and heterogeneity in patient series. A consensus on classification, treatment protocols, and outcome is needed in order to improve reliability of future studies

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1

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.

Angiogenesis is a key factor in early stages of wound healing and is crucial for tissue regeneration. Gold standard for large bone defect treatment is the transplantation of autologous bone grafts, but is not entirely satisfying (e.g. limited amount). Cell therapies and tissue engineering approaches may overcome these problems by using cells and autologous blood components obtainable by less invasive procedures. Pre-clinical studies previously showed promising results combining endothelial progenitor cells (EPCs) and mesenchymal stem cell (MSCs) in polyurethane scaffolds in presence of PRP (1). A systemic investigation of the chemical and mechanical characteristics of different PRP gels formulations suggested their potential use as sustained autologous growth factor delivery system (2). Here we investigate PRP hydrogels as autologous injectable cell delivery systems for EPCs and MSCs and their efficacy in promoting fast neo-vascularization for bone repair applications. PRP hydrogel and corresponding platelet lysate (PL) were produced from platelet concentrates as described before (3). MSCs were isolated by Ficoll-Paque centrifugation from human bone marrow (EK_regensburg12-101-0127), and cultured in alpha MEM containing 10% FCS and 5 ng/mL basic-FGF (GIBCO). EPCs (CD133+/CD34+) were isolated from MSC fractions using magnetic-activated cell sorting (MACS®) and further cultured in IMDM (GIBCO) containing 5% FCS and 5% PL. GFP positive HUVECs are from Angio-Proteomie, (Boston, USA). Prior to gel encapsulation, MSC and EPCs were pre-stained using PKH26-red® and PKH67-green® respectively. Cells in different proportions were encapsulated in 3D PRP gels, in FDA approved Fibrin gels and in Matrigel®. The gels were cultured in Ibidi microwells placed in an onstage incubator linked to an EVOS Auto Cell Imaging System. The cellular network formation capacity of HUVEC or EPCs and MSC in different proportions was analyzed for the 3 types of hydrogels using time lapse movies recorded over a period of 14 days. Parallel cultures were performed in a classical cell culture CO. 2. incubator and sample gels were taken at different time points for additional immunostaining and gene expression analysis. Preliminary results indicate high cell viability in all of the three tested gels. PRP hydrogels present a favorable environment for the formation of a 3 dimensional cellular network in cell co-culture. The formation of these networks was apparent as early as 4 days after seeding. Networks increase in complexity and branching over time. The same was observed when cells were embedded in Matrigel®, which is known for its pro-angiogenic properties. Further experiments are currently in process looking at the involvement of MSCs in this process and the effect of PRP 3D co-culture on their differentiation. PRP was previously shown as a potent growth factor delivery system for tissue engineering. In the present work, the high cell viability together with the 3 dimensional capillary-like networks observed at early time points suggest that PRP can also be used as an autologous cell delivery and pro-angiogenic system for bone tissue repair

Objectives

The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics.

This article is based on the analysis of surgical treatment peculiarities of 641 patients with post-osteomyelitis long bones defects. The average age of patients at the time of hospital admission was 32,4 ± 0,7 and ranged from 4 to 70 years. Most of them were people of active working age (476 (74.3%)) and male (523 (81.1%)).

In this observation group 566 (88.3%) patients had the osteomyelitis process of the traumatic origin, including post-surgical (n = 155) and post-gunshot injuries (n = 13). Chronic hematogenous osteomyelitis was diagnosed in 75 (11.7%) patients. Most patients had lower extremity bones problems, including 444 tibia defects and 142 femoral bone defects. Much fewer patients had the osteomyelitis process of the upper extremity (humerus, radius, ulnar bone – 18, 19 and 18 respectively).

Purulent necrotic process was accompanied by nonunion bone fragments in 160 (24%) patients, delayed union in 95 (14.6%) patients, false joint in 178 (27.6%) patients, segmental bone defect in 75 (11 5%) patients and bones union with edge defects and cavities in 143 (22.3%) patients.

340 (53%) patients were operated using the method of free bone grafting, and 301 (47%) patients were operated using the distraction method.

The need to use the bilocal for external fixation on upper extremities occurs quite seldom (twice in our observations). Even when there is an upper extremity bone defect of several centimeters the preference should be given not to bilocal external fixation.

When treating the lower extremities taking the above mentioned into consideration, segmental defects predominated, that is why the bilocal distraction-compression method of surgical treatment prevailed (98.6%).

Thus, the main method of upper extremities long bones defects replacement is free bone grafting with segment fixation by the external fixation device, for lower extremities the is not-free main Ilizarov method, which allows to get positive results in 84.6% of patients with femoral bone problems and in 96.4% of tibia problems, mainly due to one-step treatment, directed simultaneously to inflammatory process elimination and maximum possible anatomical and functional restoration of the affected extremity.

Bone loss in the proximal tibia and distal femur is frequently encountered in revision knee replacement surgery. The various options for dealing with this depend on the extent of any bone loss. We present our results with the use of cementless metaphyseal metal sleeves in 103 patients (104 knees) with a mean follow-up of 43 months (30 to 65). At final follow-up, sleeves in 102 knees had good osseointegration. Two tibial sleeves were revised for loosening, possibly due to infection.

The average pre-operative Oxford Knee Score was 23 (11 to 36) and this improved to 32 (15 to 46) post-operatively. These early results encourage us to continue with the technique and monitor the outcomes in the long term.

Cite this article: Bone Joint J 2013;95-B:1640–4.

Purpose. To identify the causes of failure after unicompartmental knee arthroplasty (UKA), and to evaluate considerations for surgical procedures and the results of revision total knee arthroplasty (TKA) performed after failure of UKA. Materials and Methods. Eight hundreds and fifty-two cases of UKA were performed from January 2002 to June 2011. Forty-seven cases of failures after UKA were analyzed for the cause of the failures, and thirty-five cases of revision TKA after failure were analyzed for the operative findings and surgical technique. The clinical results were measured for thirty cases which were followed-up on at least two years after TKA. The mean duration of follow-up was four years and one month after revision TKA and the mean patient age at the time of surgery was sixty-five years. Results. For the cause of failures after UKA, there were twenty-two cases of early loosening of prosthesis, seventeen cases of simple mobile bearing dislocation, five cases of infection, one case of fracture of medial tibial condyle and two cases of unknown origin pain. In operative findings of thirty-five cases of TKA after failed UKA, there were twenty-five cases of bone defect requiring treatment and the mean thickness of the defect was 10.6 mm. For the treatment of bone defect, there were five cases of autogenous bone graft, twenty-one cases of metal blocks, and one case of autogenous bone graft with metal block. The stem was used in tibial implants for nineteen cases, and one case of use in tibial and femoral implants. For thirty cases where follow ups were possible at least two years after operation, the mean knee score was improved from 68.2 to 85.2 and the mean knee function score was improved from 67.7 to 78.0 at the last follow-up, respectively. The mean range of knee motion was 107.2° pre-operatively, which was recovered to 120.7° after the operation. The mean tibiofemoral angle was changed from 1.7° of valgus to 5.2° of valgus. Conclusion. As shown in this study, the tibial bone defect was the most important problem in revision TKA after failure of UKA. Therefore, proper indication and accurate surgical technique using autogenous bone graft, metal block and stemmed implants would be able to achieve satisfactory results in revision TKA after failure of UKA

This prospective randomized multicenter study compares two methods of bone defect treatment in tibial plateau fractures: a bioresorbable calcium phosphate paste (Alpha-BSM) that hardens at body temperature to give structural support versus Autogenous iliac bone graft (AIBG). One hundred and eighteen patients were enrolled with a 2:1 randomization, Alpha-BSM to AIBG. There was a significant increased rate of non-graft related adverse affects and a higher rate of late articular subsidence (three to nine month period) in the AIBG group. A bioresorbable calcium phosphate material is recommended in preference to the gold standard of AIBG for bone defects in tibial plateau fractures. This prospective randomized multicenter study was undertaken to compare two methods of bone defect treatment: a bioresorbable calcium phosphate paste (Alpha-BSM –DePuy, Warsaw, IN) that hardens at body temperature to give structural support and is gradually resorbed by a cell-mediated bone regenerating mechanism versus Autogenous iliac bone graft (AIBG). One hundred and eighteen adult acute closed tibial plateau fractures, Schatzker grade two to six were enrolled prospectively from thirteen study sites in North America from 1999 to 2002. Randomization occurred at surgery with a FDA recommendation of a 2–1 ratio, Alpha BSM (seventy-eight fractures) to AIBG (forty fractures). Only internal fixation with standard plate and screw constructs was permitted. Follow-up included standard radiographs and functional studies at one year, with a radiologist providing independent radiographic review. The two groups exhibited no significant differences in randomization as to age, sex, race, fracture patterns or fracture healing. There was however, a significant increased rate of non-graft related adverse affects in the AIBG group. There was an unexpected significant finding of a higher rate of late articular subsidence in the three to nine month period in the AIBG group. Recommendations for the use of AIBG for bone defects in tibial plateau fractures should be discouraged in favor of bioresorbable calcium phosphate material with the properties of Alpha BSM. We believe further randomized studies using AIBG as a control group for bone defect support of articular fractures are unjustified. A bioresorbable calcium phosphate material is recommended in preference to the gold standard of AIBG for bone defects in tibial plateau fractures. Funding: DePuy, Warsaw, IN

Aims: To evaluate the results and complications of Ilizarov bone transport method for the treatment of long bones defects. Methods: Between 1990 and 2001 the Ilizarov intercalary bone transport method was applied to treat 44 patients with segmental bone loss of the femur and tibial. The series comprised 30 males and 14 females with an average age of 33 years (range 17–68 years). Two different types of treatment were used: Ç monofocal È technique, for small bone defects up to 4 cm and Ç bifocal È technique, for large bone defects (4–20 cm). The mean bone defect was 10 cm (range 3–18cm), while mean external þxation time was 8.6 months (range 3–24 months). The mean consolidation index of the distraction gap was 23 days/cm (range 18–27 d/cm). Mean follow up period after frame removal was 4 years (range 1–11 years). Results: The bone results were rated as excellent in 33 patients (74%), good in 6 (13%) and poor in 1 (2%). The functional results were rated as excellent in 7 patients (16%), good in 29 (66%), fair in 5 (11%), and poor in 3 (7%). Pin tract infection was the most common complication. The late complications included axial deformities, re-fractures and joint stiffness. Conclusions: The Ilizarov method is still an effective technique for bone defects treatment; the main disadvantage is the prolonged external þxation time

Aims: Study our experience and short term results using a mix of osteoconductive (HA) and osteoinductive (AGF) materials. Methods: From October 2001 until June 2002, we have treated bone defects in 9 patients. Seven male and 2 female. Mean age 10.4 years (range 4–18 years). Mean follow-up: 5.6 months (range 3–9 months). AGF was obtained after autologous blood centrifugation according to blood volume, knowing the patient height and weight (Nadler Score). AGF was obtained through previous concentrate of platelets and red cells, with a further concentration, reducing its volume to 1/3. 10 c.c. of thrombin (500 UI) and HA (500R) were added, just before applying it to the patient. Total surgery time for preparation AGF was 20–30 minutes. Clinical cases treated were: varus osteotomy in Perthes (1 case- 11%); curettage in osteomyelitis (2 cases- 22%); essential cyst, after conventional corticoid treatment failure (2 cases- 22%); forearm pseudoarthrosis (2 cases- 23%) and triple arthodesis by valgus pronated spastic foot (2 cases- 22%). We never use autologous iliac graft with AGF- HA. Results: We have obtained radiological and clinical consolidation in all bone defects after 3–4 months. Radiological success is not clear after 4 months in one of the osteomyelitis cases (12’5%). Conclusions: 1. The iliac graft harvest morbility is about 9.4%- 49%. 2. A 2nd approach is avoided in children and adolescents. 3. With the use of AGF- HA we avoid morbility, diseases transmission, reduced surgery time and offer an alternative to autologous grafting.