Additive manufacturing, also known as 3D printing, has emerged over the past 3 decades as a disruptive technology for rapid prototyping and manufacturing. Vat polymerization, powder bed fusion, ...material extrusion, and binder jetting are distinct technologies of additive manufacturing, which have been used in a wide variety of fields, including biomedical research and tissue engineering. The ability to print biocompatible, patient-specific geometries with controlled macro- and micro-pores, and to incorporate cells, drugs and proteins has made 3D-printing ideal for orthopaedic applications, such as bone grafting. Herein, we performed a systematic review examining the fabrication of calcium phosphate (CaP) ceramics by 3D printing, their biocompatibility
in vitro
, and their bone regenerative potential
in vivo
, as well as their use in localized delivery of bioactive molecules or cells. Understanding the advantages and limitations of the different 3D printing approaches, CaP materials, and bioactive additives through critical evaluation of
in vitro
and
in vivo
evidence of efficacy is essential for developing new classes of bone graft substitutes that can perform as well as autografts and allografts or even surpass the performance of these clinical standards.
Abstract Orthopaedic devices are the most common surgical devices associated with implant-related infections and Staphylococcus aureus ( S. aureus ) is the most common causative pathogen in chronic ...bone infections (osteomyelitis). Treatment of these chronic bone infections often involves combinations of antibiotics given systemically and locally to the affected site via a biomaterial spacer. The gold standard biomaterial for local antibiotic delivery against osteomyelitis, poly(methyl methacrylate) (PMMA) bone cement, bears many limitations. Such shortcomings include limited antibiotic release, incompatibility with many antimicrobial agents, and the need for follow-up surgeries to remove the non-biodegradable cement before surgical reconstruction of the lost bone. Therefore, extensive research pursuits are targeting alternative, biodegradable materials to replace PMMA in osteomyelitis applications. Herein, we provide an overview of the primary clinical treatment strategies and emerging biodegradable materials that may be employed for management of implant-related osteomyelitis. We performed a systematic review of experimental biomaterials systems that have been evaluated for treating established S. aureus osteomyelitis in an animal model. Many experimental biomaterials were not decisively more efficacious for infection management than PMMA when delivering the same antibiotic. However, alternative biomaterials have reduced the number of follow-up surgeries, enhanced the antimicrobial efficacy by delivering agents that are incompatible with PMMA, and regenerated bone in an infected defect. Understanding the advantages, limitations, and potential for clinical translation of each biomaterial, along with the conditions under which it was evaluated (e.g. animal model), is critical for surgeons and researchers to navigate the plethora of options for local antibiotic delivery.
Total knee arthroplasty (TKA) is one of the most common and costly surgical procedures performed in the United States.
To examine longitudinal trends in volume, utilization, and outcomes for primary ...and revision TKA between 1991 and 2010 in the US Medicare population.
Observational cohort of 3,271,851 patients (aged ≥65 years) who underwent primary TKA and 318 563 who underwent revision TKA identified in Medicare Part A data files.
We examined changes in primary and revision TKA volume, per capita utilization, hospital length of stay (LOS), readmission rates, and adverse outcomes.
Between 1991 and 2010 annual primary TKA volume increased 161.5% from 93,230 to 243,802 while per capita utilization increased 99.2% (from 31.2 procedures per 10,000 Medicare enrollees in 1991 to 62.1 procedures per 10,000 in 2010). Revision TKA volume increased 105.9% from 9650 to 19,871 while per capita utilization increased 59.4% (from 3.2 procedures per 10,000 Medicare enrollees in 1991 to 5.1 procedures per 10,000 in 2010). For primary TKA, LOS decreased from 7.9 days (95% CI, 7.8-7.9) in 1991-1994 to 3.5 days (95% CI, 3.5-3.5) in 2007-2010 (P < .001). For primary TKA, rates of adverse outcomes resulting in readmission remained stable between 1991-2010, but rates of all-cause 30-day readmission increased from 4.2% (95% CI, 4.1%-4.2%) to 5.0% (95% CI, 4.9%-5.0%) (P < .001). For revision TKA, the decrease in hospital LOS was accompanied by an increase in all-cause 30-day readmission from 6.1% (95% CI, 5.9%-6.4%) to 8.9% (95% CI, 8.7%-9.2%) (P < .001) and an increase in readmission for wound infection from 1.4% (95% CI, 1.3%-1.5%) to 3.0% (95% CI, 2.9%-3.1%) (P < .001).
Increases in TKA volume have been driven by both increases in the number of Medicare enrollees and in per capita utilization. We also observed decreases in hospital LOS that were accompanied by increases in hospital readmission rates.
Abstract Low temperature 3D printing of calcium phosphate scaffolds holds great promise for fabricating synthetic bone graft substitutes with enhanced performance over traditional techniques. Many ...design parameters, such as the binder solution properties, have yet to be optimized to ensure maximal biocompatibility and osteoconductivity with sufficient mechanical properties. This study tailored the phosphoric acid-based binder solution concentration to 8.75 wt% to maximize cytocompatibility and mechanical strength, with a supplementation of Tween 80 to improve printing. To further enhance the formulation, collagen was dissolved into the binder solution to fabricate collagen-calcium phosphate composites. Reducing the viscosity and surface tension through a physiologic heat treatment and Tween 80, respectively, enabled reliable thermal inkjet printing of the collagen solutions. Supplementing the binder solution with 1–2 wt% collagen significantly improved maximum flexural strength and cell viability. To assess the bone healing performance, we implanted 3D printed scaffolds into a critically sized murine femoral defect for 9 weeks. The implants were confirmed to be osteoconductive, with new bone growth incorporating the degrading scaffold materials. In conclusion, this study demonstrates optimization of material parameters for 3D printed calcium phosphate scaffolds and enhancement of material properties by volumetric collagen incorporation via inkjet printing.
Abstract This manuscript will evaluate the published evidence on efficacy of organized hip fracture programs to determine if they improve patient outcomes. A detailed literature search was conducted ...to find manuscripts published in the past 20 years about organized hip fracture care programs. Seventeen programs with published results were identified from this detailed search and these were evaluated and synthesized in the following manuscript. Organized hip fracture programs offer significant benefits to patients, care providers and health systems. The more complex program designs have a more profound effect on improvement in outcomes for hip fracture patients. Most programs have reported reduced length of stay, reduced in-hospital mortality rates, and reduced complications. Some programs have reported reduced costs and reduced readmission rates after implementing an organized hip fracture program.
Study question Can the length of hospital stay for hip fracture affect a patient’s risk of death 30 days after discharge?Methods In a retrospective cohort study, population based registry data from ...the New York Statewide Planning and Research Cooperative System (SPARCS) were used to investigate 188 208 patients admitted to hospital for hip fracture in New York state from 2000 to 2011. Patients were aged 50 years and older, and received surgical or non-surgical treatment. The main outcome measure was the mortality rate at 30 days after hospital discharge.Study answer and limitations Hospital stays of 11-14 days for hip fracture were associated with a 32% increased odds of death 30 days after discharge, compared with stays lasting one to five days (odds ratio 1.32 (95% confidence interval 1.19 to 1.47)). These odds increased to 103% for stays longer than 14 days (2.03 (1.84 to 2.24)). Other risk factors associated with early mortality included discharge to a hospice facility, older age, metastatic disease, and non-surgical management. The 30 day mortality rate after discharge was 4.5% for surgically treated patients and 10.7% for non-surgically treated patients. These findings might not be generalizable to populations in other US states or in other countries. The administrative claims data used could have been incomplete or include inaccurate coding of diagnoses and comorbid conditions. The database also did not include patient socioeconomic status, which could affect access to care to a greater extent in New York state than in European countries. Specific cause of death was not available because few autopsies are performed in this population. What this study adds By contrast with recent findings in Sweden, decreased length of hospital stay for hip fracture was associated with reduced rates of early mortality in a US cohort in New York state. This could reflect critical system differences in the treatment of hip fractures between Europe and the USA.Funding, competing interests, data sharing University of Rochester grant from the Clinical Translational Science Institute for statistical analyses used in this work (National Institutes of Health (UL1 TR000042)) and the National Institutes of Health (K-08 AR060164-01A). No competing interests declared. Data may be obtained through SPARCS at https://www.health.ny.gov/statistics/sparcs/access/.
ABSTRACT
Musculoskeletal infections (MSKI) remain the bane of orthopedic surgery, and result in grievous illness and inordinate costs that threaten healthcare systems. As prevention, diagnosis, and ...treatment has remained largely unchanged over the last 50 years, a 2nd International Consensus Meeting on Musculoskeletal Infection (ICM 2018, https://icmphilly.com) was completed. Questions pertaining to all areas of MSKI were extensively researched to prepare recommendations, which were discussed and voted on by the delegates using the Delphi methodology. The questions, including the General Assembly (GA) results, have been published (GA questions). However, as critical outcomes include: (i) incidence and cost data that substantiate the problems, and (ii) establishment of research priorities; an ICM 2018 research workgroup (RW) was assembled to accomplish these tasks. Here, we present the result of the RW consensus on the current and projected incidence of infection, and the costs per patient, for all orthopedic subspecialties, which range from 0.1% to 30%, and $17,000 to $150,000. The RW also identified the most important research questions. The Delphi methodology was utilized to initially derive four objective criteria to define a subset of the 164 GA questions that are high priority for future research. Thirty‐eight questions (23% of all GA questions) achieved the requisite > 70% agreement vote, and are highlighted in this Consensus article within six thematic categories: acute versus chronic infection, host immunity, antibiotics, diagnosis, research caveats, and modifiable factors. Finally, the RW emphasizes that without appropriate funding to address these high priority research questions, a 3rd ICM on MSKI to address similar issues at greater cost is inevitable.
Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly ...high.
is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including:
abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone. In contrast,
intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against
, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies (MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.
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