Bone and metal - an orthopaedic perspective on osseointegration of metals

The area of implant osseointegration is of major importance, given the predicted significant rise in the number of orthopaedic procedures and an increasingly ageing population. Osseointegration is a complex process involving a number of distinct mechanisms affected by the implant bulk properties and surface characteristics. Our understanding and ability to modify these mechanisms through alterations in implant design is continuously expanding. The following review considers the main aspects of material and surface alterations in metal implants, and the extent of their subsequent influence on osseointegration. Clinically, osseointegration results in asymptomatic stable durable fixation of orthopaedic implants. The complexity of achieving this outcome through incorporation and balance of contributory factors is highlighted through a clinical case report

Bone tissue engineering

Medical advances have led to a welcome increase in life expectancy. However, accompanying longevity introduces new challenges: increases in age-related diseases and associated reductions in quality of life. The loss of skeletal tissue that can accompany trauma, injury, disease or advancing years can result in significant morbidity and significant socio-economic cost and emphasise the need for new, more reliable skeletal regeneration strategies. To address the unmet need for bone augmentation, tissue engineering and regenerative medicine have come to the fore in recent years with new approaches for de novo skeletal tissue formation. Typically, these approaches seek to harness stem cells, innovative scaffolds and biological factors that promise enhanced and more reliable bone formation strategies to improve the quality of life for many. This review provides an overview of recent developments in bone tissue engineering focusing on skeletal stem cells, vascular development, bone formation and the translation from preclinical in vivo models to clinical delivery

Human Skeletal Stem Cell Response to Multiscale Topography Induced by Large Area Electron Beam Irradiation Surface Treatment

The healthcare socio-economic environment is irreversibly changing as a consequence of an increasing aging population, consequent functional impairment, and patient quality of life expectations. The increasing complexity of ensuing clinical scenarios compels a critical search for novel musculoskeletal regenerative and replacement strategies. While joint arthroplasty is a highly effective treatment for arthritis and osteoporosis, further innovation and refinement of uncemented implants are essential in order to improve implant integration and reduce implant revision rate. This is critical given financial restraints and the drive to improve cost-effectiveness and quality of life outcomes. Multi-scale modulation of implant surfaces, offers an innovative approach to enhancement in implant performance. In the current study, we have examined the potential of large area electron beam melting to alter the surface nanotopography in titanium alloy (Ti6Al4V). We evaluated the in vitro osteogenic response of human skeletal stem cells to the resultant nanotopography, providing evidence of the relationship between the biological response, particularly Collagen type I and Osteocalcin gene activation, and surface nanoroughness. The current studies demonstrate osteogenic gene induction and morphological cell changes to be significantly enhanced on a topography Ra of ~40 nm with clinical implications therein for implant surface treatment and generation

Nanopatterned titanium implants accelerate bone formation in vivo

Accelerated de novo formation of bone is a highly desirable aim of implants targeting musculoskeletal injuries. To date, this has primarily been addressed by biologic factors. However, there is an unmet need for robust, highly reproducible yet economic alternative strategies that strongly induce an osteogenic cell response. Here, we present a surface engineering method of translating bioactive nanopatterns from polymeric in vitro studies to clinically relevant material for orthopedics: three-dimensional, large area metal. We use a titanium-based sol–gel whereby metal implants can be engineered to induce osteoinduction both in vitro and in vivo. We show that controlled disordered nanotopographies presented as pillars with 15–25 nm height and 100 nm diameter on titanium dioxide effectively induce osteogenesis when seeded with STRO-1-enriched human skeletal stem cells in vivo subcutaneous implantation in mice. After 28 days, samples were retrieved, which showed a 20-fold increase in osteogenic gene induction of nanopatterned substrates, indicating that the sol–gel nanopatterning method offers a promising route for translation to future clinical orthopedic implants

Bone and metal interface - an orthopaedic perspective on osseointegration of metal implants

Introduction: The health care socio-economic Environment is changing due to the population ageing, rising resultant functional impairment and patient quality of life expectations. These factors introduce increasing complexity of ensuing clinical scenarios, compelling a critical search for novel musculoskeletal regenerative and replacement strategies. Although joint arthroplasty is a highly effective treatment for arthritis, further innovation and refinement of uncemented implants are essential in order to improve implant integration and reduce the revision rate. This is critical within the current NHS environment of financial restraints and the drive to improve cost-effectiveness in arthroplasty.Methods: Biological skeletal stem cell (SSC)-mediated responses to surface nanotopographies were investigated. Passage one STRO 1 SSCs were cultured on nanotopographies in vitro, while in vivo examination of nanotopographies was conducted in subcutaneous mouse and calvarial rat models.Results: The following results were observed in relation to a range of surface modifying techniques:1. Lithography -nanotopographies containing 20 nm tall pillars with near-square surface pattern arrangement generated significant enhancement of osteogenic gene induction (ALP, Collagen type I, OPN and OCN), osteogenic morphology and extracellular OPN synthesis in vitro and in vivo. In addition, histological evidence of collagen fibre organisation and early de novo mineralisation was observed in vivo. 2. Large Area Electron Beam melting -in vitro SSC osteogenic morphological alterations, bone matrix gene activation and OPN synthesis were directly correlated to the surface roughness within Ra range of 20-60 nm, with increasing Ra resulting in enhancement of osteogenic differentiation.3. Thermal oxidation -nanowires 300 generated significant enhancement of osteogenic gene expression, osteogenic morphology, and OPN and Collagen type I protein synthesis in vitro. Significant enhancement of bone volume deposition at implant/bone interface was observed in vivo.4. Electrochemical Jet Machining -nanotopographical elements of hierarchical scale texture triggered enhanced osteogenic gene expression.Conclusions: This work has demonstrated the ability of various nanotopographical surface-finishes to trigger an enhanced SSC-mediated osteogenic response, providing a clear rational for their potential application in orthopaedic implant <br/

Anastomotic leak rate and outcome for laparoscopic intra-corporeal stapled anastomosis

Objectives: A prospective audit of all patients undergoing laparoscopic surgery with the intention of primary colonic left-sided intracorporeal stapled anastomosis to identify the clinical anastomotic leak rate on an intention to treat basis. Methods: All patients undergoing laparoscopic colorectal surgery resulting in left-sided stapled anastomosis were included. All operations were conducted by the same surgical team with the same pre-operative preparation and surgical technique. The factors analysed for this audit were patient demographics (age and sex), indication for operation, procedure performed, height of anastomosis, leak rate and the outcome, inpatient stay, mortality, rate of defunctioning stomas, and rate of conversion to open procedure. Results: Eighty-four patients (49 females, 35 males; median age 70 years, range 19-89 years) underwent colonic procedures with left-sided intracorporeal stapled anastomosis. An intra-operative air leak was evident in one patient, whose anastomosis was oversewn intracorporeally and defunctioned by ileostomy. There were only two clinically evident anastomotic leaks post-operatively (2.9&#x0025;). One patient died of overwhelming sepsis within 48h of re-operation: Seven patients (8.3&#x0025;) had a primary defunctioning stoma, with two further stomas formed due to anastomotic leakage. Five cases (6&#x0025;) were converted to open surgery. The median post-operative stay was six days, range 2-23. Thirty-day mortality was 50&#x0025; in the leak group and 0&#x0025; in the non-leak group. Conclusion: We believe that this study demonstrates that the anastomotic leak rate from intra-corporeal laparoscopic anastomosis is no greater than for open surgery or laparoscopic surgery with extra-corporeal anastomosis

Anastomotic leak rate and outcome for laparoscopic intra-corporeal stapled anastomosis

Aims :A prospective clinical audit of all patients undergoing laparoscopic surgery with the intention of primary colonic left-sided intracorporeal stapled anastomosis to identify the rate of anastomotic leaks on an intention to treat basis with or without defunctioning stoma. Materials and Methods : All patients undergoing laparoscopic colorectal surgery resulting in left-sided stapled anastomosis were included with no selection criteria applied. All operations were conducted by the same surgical team and the same preparation and intraoperative methods were used. The factors analyzed for this audit were patient demographics (age and sex), indication for operation, procedure performed, height of anastomosis, leak rate and the outcome, inpatient stay, mortality, rate of defunctioning stomas, and rate of conversion to open procedure. Results for anastomotic leakage were compared with known results from the Wessex Colorectal Audit for open colorectal surgery. Results : A total of 69 patients (43 females, 26 males; median age 69 years, range 19 - 86 years) underwent colonic procedures with left-sided intracorporeal stapled anastomoses. Of these, 14 patients underwent reversal of Hartmann&#x2032;s, 42 - Anterior Resection, 11 - Sigmoid Colectomy, 2 - Left Hemicolectomy. Excluding reversals of Hartmann&#x2032;s, 29 operations were performed for malignant and 26 for benign disease. Five patients were defunctioned, and 3 were subsequently reversed. The median height of anastomosis was 12 cm, range 4 - 18 cm from anal verge as measured either intra-operatively, or by rigid sigmoidoscopy post-operatively. Four cases were converted to open surgery. There was 1 post-operative death within 30 days. There was 1 anastomotic leak (the patient that died), and 1 patient developed a colo-vesical fistula. Median post-operative stay was 7 days, range 2-19. Conclusion : This clinical audit confirms that the anastomotic leak rate for left-sided colorectal stapled anastomosis is no worse than that for open surgery. Therefore the decision making process for defunctioning stoma should be guided by the same principles as open surgery

Anastomotic leak rate and outcome for laparoscopic intra-corporeal stapled anastomosis

Objectives: A prospective audit of all patients undergoing laparoscopic surgery with the intention of primary colonic left-sided intracorporeal stapled anastomosis to identify the clinical anastomotic leak rate on an intention to treat basis. Methods: All patients undergoing laparoscopic colorectal surgery resulting in left-sided stapled anastomosis were included. All operations were conducted by the same surgical team with the same pre-operative preparation and surgical technique. The factors analysed for this audit were patient demographics (age and sex), indication for operation, procedure performed, height of anastomosis, leak rate and the outcome, inpatient stay, mortality, rate of defunctioning stomas, and rate of conversion to open procedure. Results: Eighty-four patients (49 females, 35 males; median age 70 years, range 19-89 years) underwent colonic procedures with left-sided intracorporeal stapled anastomosis. An intra-operative air leak was evident in one patient, whose anastomosis was oversewn intracorporeally and defunctioned by ileostomy. There were only two clinically evident anastomotic leaks post-operatively (2.9%). One patient died of overwhelming sepsis within 48h of re-operation: Seven patients (8.3%) had a primary defunctioning stoma, with two further stomas formed due to anastomotic leakage. Five cases (6%) were converted to open surgery. The median post-operative stay was six days, range 2-23. Thirty-day mortality was 50% in the leak group and 0% in the non-leak group. Conclusion: We believe that this study demonstrates that the anastomotic leak rate from intra-corporeal laparoscopic anastomosis is no greater than for open surgery or laparoscopic surgery with extra-corporeal anastomosis

Application of 3D-printed patient-specific skeletal implants augmented with autologous skeletal stem cells

Joint replacements have proved a medical success providing symptomatic relief and return to mobility in many patients with arthritis. However, multiple revision surgeries due to joint failure can result in complex revision scenarios with significant bone tissue loss, in an elderly population, which poses a significant clinical challenge. Computer-aided design-computer-assisted manufacturing (CAD-CAM) prototyped bespoke implants are currently being used as an alternative and innovative approach for joint restoration in salvage cases, while the incorporation of autologous skeletal stem cells to optimize regenerative capacity can enhance implant osseointegration. We present a case series of 11 patients with severe disability and significant bone loss due to failed joint replacements. The choice of CAD-CAM prototyped joint implants enhanced with autologous skeletal stem cells resulted in significant patient-reported clinical and radiological improvements.</p