Blood transfusion, organ and bone marrow transplantation and allogeneic tissue grafting create the potential for significant immunological challenges through the introduction of non-genetically identical major (HLA) and minor histocompatibility antigens (“allo-antigens”) into the body. Strategies to avoid the complications of immune responses against allo-antigens (transfusion reactions, rejection and graft versus host disease) include HLA matching, immunosuppressive therapies and immune tolerance promoting protocols. In the case of allogeneic mesenchymal stem/stromal cells (allo-MSC), it was initially believed that their combined properties of low HLA expression and inherent immune modulatory functions would render them invisible to the host immune system and, therefore, capable of being permanently accepted without further interventions. For clinical indications such as bone and tendon repair, in which permanent engraftment of allo-MSC or MSC-derived tissue constructs is particularly desirable, this model of “immune privilege” seemed almost too good to be true – and indeed, a decade of experimental research in this area has now convincingly demonstrated that allo-MSC typically elicit cellular (T-cell) and humoral (B-cell/antibody) immune responses in immunocompetent hosts – raising concern about their safety and long-term efficacy in human conditions. However, questions related to the immunogenicity of allo-MSC have evolved beyond a simple yes/no scenario to involve interesting observations and concepts about the potency, diversity, duration, functional characteristics and even potential clinical benfits of immunological responses to allo-MSC. In this presentation, I will summarise and critically evaluate current understanding of allo-MSC immunogenicity under experimental and clinical trial conditions with an emphasis on the implications for orthopaedic therapeutics.

3D imaging is commonly employed in the surgical planning and management of bony deformity. The advent of desktop 3D printing now allows rapid in-house production of specific anatomical models to facilitate surgical planning. The aim of this pilot study was to evaluate the feasibility of creating 3D printed models in a university hospital setting.

For requested cases of interest, CT DICOM images on the local NHS Picture Archive System were anonymised and transferred. Images were then segmented into 3D models of the bones, cleaned to remove artefacts, and orientated for printing with preservation of the regions of interest. The models were printed in polylactic acid (PLA), a biodegradable thermoplastic, on the CubeX Duo 3D printer.

PLA models were produced for 4 clinical cases; a complex forearm deformity as a result of malunited childhood fracture, a pelvic discontinuity with severe acetabular deficiency following explantation of an infected total hip replacement, a chronically dislocated radial head causing complex elbow deformity as a result of a severe skeletal dysplasia, and a preoperative model of a deficient proximal tibia as a result of a severe tibia fracture. The models materially influenced clinical decision making, surgical intervention planning and required equipment. In the case of forearm an articulating model was constructed allowing the site of impingement between radius and ulnar to be identified, an osteotomy was practiced on multiple models allowing elimination of the block to supination. This has not previously been described in literature. The acetabulum model allowed pre-contouring of a posterior column plate which was then sterilised and eliminated a time consuming intraoperative step.

While once specialist and expensive, in house 3D printing is now economically viable and a helpful tool in the management of complex patients.

Introduction

Nonunions pose complications in fracture management that can be treated using electrical stimulation (ES). Bone marrow mesenchymal stem cells (BMMSCs) are essential in fracture healing, although the effects of different clinical ES waveforms available in clinical practice on BMMSCs cellular activities is unknown.

Delayed facture repair and bony non-unions pose a clinical challenge. Understandably, novel methods to enhance bone healing have been studied by researchers worldwide. Electrical stimulation (ES) has shown to be effective in enhancing bone healing, however the best wave form and mechanism by which it stimulates osteoblasts remains unknown. Interestingly, it is considered that osteoblast activity depends on specific waveforms applied. Therefore, the aim of this study was to evaluate whether particular waveforms have a differential effect on osteoblast activity.

An osteoblast cell line was electrically stimulated with either capacitive coupling (CC) or a novel degenerate wave (DW) using a unique in vitro ES system. Following application of both waveforms, the extent of cytotoxicity, proliferation, differentiation and mineralisation of the osteoblasts were assessed using various assays. Differentiation and mineralisation were further analysed using quantitative real-time PCR (qRT PCR) and immunocytochemistry (ICC).

DW stimulation significantly enhanced the differentiation of the osteoblasts compared to CC stimulation, with increased protein and gene expression of alkaline phosphatase and type 1 collagen at 28 hours (p < 0.01). DW significantly enhanced the mineralisation of the osteoblasts compared to CC with greater Alizarin Red S staining and gene expression of osteocalcin, osteonectin, osteopontin and bone sialoprotein at 28 hours (p < 0.05). Moreover, immunocytochemical assays showed higher osteocalcin expression after DW stimulation compared to CC at 28 hours.

The reintroduction of hip resurfacing has raised the possibility of whether it could offer a better outcome in sporting and work activity after surgery compared to total hip replacement.

Questionnaires were analysed from 125 total hip replacement (THR) and 108 hip resurfacing (HR) patients regarding participation in sport in the year after their surgery and returning to work they were employed at prior to their surgery. The two groups had similar average age (61 vs 60) and pre-operative Oxford hip scores (41 vs 38).

Seventy-one of one-hundred and twenty-five THR patients compared to 76/108 HR patients participated in sporting activity in the year after their surgery. When including only patients that played sport before their surgery 54/75 THR and 66/83 HR patients returned to same sporting activity level after their surgery. Of the patients that worked before surgery 35/44 THR patients compared to 70/74 HR patients returned work to after their surgery.

There is significant difference quantity of patients participating in sporting activity after HR and THR (fishers exact test, p value=0.04). However there is no significant difference in quantity of patients returning to sporting activity after HR or THR including only patients that played sport before their surgery (fishers exact test, p value=0.35). There is a significant difference in the quantity of patients returning to work activity after HR and THR (fishers exact test, p value= 0.02). HR has a better outcome in patients participating in sport after surgery compared to THR however there is no benefit for patients that are active pre-operatively. More patients return to work after HR than THR.

Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting.

There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone.