Effect of surgeon-specific feedback on surgical outcomes: a systematic review of the literature.

BACKGROUND: Surgeon-specific outcome reporting provides an opportunity for quality assurance and improved surgical results. It is becoming increasingly prevalent and remains contentious amongst surgeons. The purpose of this systematic review was to evaluate the extent to which published literature supports the concept that feedback of surgeon-level outcomes reduces morbidity and/or mortality. No systematic reviews have previously been completed on this subject. METHODS: Medline and Embase were systematically searched for studies published prior to the 1st of January 2022. Feedback was defined as a summary of clinical performance over a specified period of time provided in written, electronic or verbal format. Studies were required to provide surgeon-specific feedback to multiple individual consultant surgeons with the primary purpose being to determine if feedback improved outcomes. Primary outcome(s) needed to relate to surgical outcomes as opposed to process measures only. All surgical specialties and procedures were eligible for inclusion. RESULTS: Seventeen studies were included in the review, traversing a wide range of specialties and procedures. Sixteen were non-randominsed and one randomized. Fifteen were before and after studies. The balance of the non-randomized studies support the concept that provision of surgeon-specific feedback can improve surgical outcomes, while the single randomized study suggests feedback may not be effective. CONCLUSIONS: This systematic review supports the use of surgeon-level feedback to improve outcomes. The strength of this finding is limited by reliance on before and after studies, further randomized studies on this subject would be insightful.

Survey of New Zealand Arthroplasty Surgeons on Surgeon-Level Outcome Reporting.

BACKGROUND: Surgeon-specific outcome monitoring has become increasingly prevalent over the last 3 decades. The New Zealand Orthopaedic Association monitors individual surgeon performance through 2 mechanisms: arthroplasty revision rates derived from the New Zealand Joint Registry and a practice visit program. Despite remaining confidential, surgeon-level outcome reporting remains contentious. The purpose of this survey was to evaluate the opinions of hip and knee arthroplasty surgeons in New Zealand on the perceived importance of outcome monitoring, current methods used to evaluate surgeon-specific outcomes, and potential improvements identified through literature review and discussion with other registries. METHODS: The survey consisted of 9 questions on surgeon-specific outcome reporting, using a five-point Likert scale, and 5 demographic questions. It was distributed to all current hip and knee arthroplasty surgeons. There were 151 hip and knee arthroplasty surgeons who completed the survey, a response rate of 50%. RESULTS: Respondents agreed that monitoring arthroplasty outcomes is important and that revision rates are an acceptable measure of performance. Reporting risk-adjusted revision rates and more recent timeframes were supported, as was including patient-reported outcomes when monitoring performance. Surgeons did not support public reporting of surgeon-level or hospital-level outcomes. CONCLUSION: The findings of this survey support the use of revision rates to confidentially monitor surgeon-level arthroplasty outcomes and suggest that concurrent use of patient-reported outcome measures would be acceptable.

The Strongest Oxford Knee Score Predictors of Subsequent Revision are "Overall Pain," "Limping When Walking," and "Knee Giving Way".

BACKGROUND: The Oxford Knee Score (OKS) is used to measure knee arthroplasty outcomes; however, it is unclear which questions are more relevant. Our aims were to (1) identify which OKS question(s) were the strongest predictors of subsequent revision and (2) compare the predictive ability of the "pain" and "function" domains. METHODS: All primary total knee arthroplasties (TKAs) and unicompartmental knee arthroplasties (UKAs) in the New Zealand Joint Registry between 1999 and 2019 with an OKS at 6 months (TKA n = 27,708; UKA n = 8,415), 5 years (TKA n = 11,519; UKA n = 3,365) or 10 years (TKA n = 6,311; UKA n = 1,744) were included. Prediction models were assessed using logistic regressions and receiver operating characteristic analyses. RESULTS: A reduced model with 3 questions ("overall pain," "limping when walking," "knee giving way") showed better diagnostic ability than full OKS for predicting UKA revision at 6 months (area under the curve [AUC]: 0.80 versus 0.78; P < .01) and 5 years (0.81 versus 0.77; P = .02), and comparable diagnostic ability for predicting TKA revision at all time points (6 months, 0.77 versus 0.76; 5 years, 0.78 versus 0.75; 10 years, 0.76 versus 0.73; all not significant), and UKA revision at 10 years (0.80 versus 0.77; not significant). The pain domain had better diagnostic ability for predicting subsequent revision for both procedures at 5 and 10 years. CONCLUSION: Questions on "overall pain", "limping when walking", and "knee giving way" were the strongest predictors of subsequent revision. Attention to low scores from these questions during follow-up may allow for prompt identification of patients most at risk of revision.

A comparison of clinical thresholds for revision following total and unicompartmental knee arthroplasty.

Unicompartmental knee arthroplasty (UKA) has higher revision rates than total knee arthroplasty (TKA). As revision of UKA may be less technically demanding than revision TKA, UKA patients with poor functional outcomes may be more likely to be offered revision than TKA patients with similar outcomes. The aim of this study was to compare clinical thresholds for revisions between TKA and UKA using revision incidence and patient-reported outcomes, in a large, matched cohort at early, mid-, and late-term follow-up. Analyses were performed on propensity score-matched patient cohorts of TKAs and UKAs (2:1) registered in the New Zealand Joint Registry between 1 January 1999 and 31 December 2019 with an Oxford Knee Score (OKS) response at six months (n, TKA: 16,774; UKA: 8,387), five years (TKA: 6,718; UKA: 3,359), or ten years (TKA: 3,486; UKA: 1,743). Associations between OKS and revision within two years following the score were examined. Thresholds were compared using receiver operating characteristic analysis. Reasons for aseptic revision were compared using cumulative incidence with competing risk. Fewer TKA patients with 'poor' outcomes (≤ 25) subsequently underwent revision compared with UKA at six months (5.1% vs 19.6%; p < 0.001), five years (4.3% vs 12.5%; p < 0.001), and ten years (6.4% vs 15.0%; p = 0.024). Compared with TKA, the relative risk for UKA was 2.5-times higher for 'unknown' reasons, bearing dislocations, and disease progression. Compared with TKA, more UKA patients with poor outcomes underwent revision from early to long-term follow-up, and were more likely to undergo revision for 'unknown' reasons, which suggest a lower clinical threshold for UKA. For UKA, revision risk was higher for bearing dislocations and disease progression. There is supporting evidence that the higher revision UKA rates are associated with lower clinical thresholds for revision and additional modes of failure.

Similar Survivorship but Different Revision Reasons for Uncemented Mobile-Bearing and Cemented Fixed-Bearing Medial UKA: A Long-Term Population-Based Cohort Study of 2,015 Patients.

BACKGROUND: Long-term survivorship and accurate characterization of revision reasons in unicompartmental knee arthroplasty (UKA) are limited by a lack of long-term data and standardized definitions of revision. The aim of this study was to identify survivorship, risk factors, and reasons for revision in a large cohort of medial UKAs with long-term follow-up (up to 20 years). METHODS: Patient, implant, and revision details for 2,015 primary medial UKAs (mean follow-up, 8 years) were recorded following systematic clinical and radiographic review. Survivorship and risk of revision were analyzed using Cox proportional hazards. Reasons for revision were analyzed using competing-risk analysis. RESULTS: Implant survivorship at 15 years was 92% for cemented fixed-bearing (cemFB), 91% for uncemented mobile-bearing (uncemMB), and 80% for cemented mobile-bearing (cemMB) UKAs (p = 0.02). When compared with cemFB, the risk of revision was higher for cemMB implants (hazard ratio [HR] = 1.9, 95% confidence interval [CI] = 1.1 to 3.2; p = 0.03). At 15 years, cemented implants had a higher cumulative frequency of revision due to aseptic loosening (3% to 4%, versus 0.4% for uncemented; p < 0.01), cemMB implants had a higher cumulative frequency of revision due to osteoarthritis progression (9% versus 2% to 3% for cemFB/uncemMB; p < 0.05), and uncemMB implants had a higher cumulative frequency of revision due to bearing dislocation (4% versus 2% for cemMB; p = 0.02). Compared with the oldest patients (≥70 years), younger patients had a higher risk of revision (<60 years: HR = 1.9, 95% CI = 1.2 to 3.0; 60 to 69 years: HR = 1.6, 95% CI = 1.0 to 2.4; p < 0.05 for both). At 15 years, there was a higher cumulative frequency of revision for aseptic loosening in these younger groups (3.2% and 3.5% versus 2.7% for ≥70 years; p < 0.05). CONCLUSIONS: Implant design and patient age were risk factors for revision of medial UKA. The findings from this study suggest that surgeons should consider using cemFB or uncemMB designs because of their superior long-term implant survivorship compared with cemMB designs. Additionally, for younger patients (<70 years), uncemMB designs had a lower risk of aseptic loosening than cemFB designs at the expense of a risk of bearing dislocation. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Associations of the Oxford Knee Score and knee arthroplasty revision at long-term follow-up.

BACKGROUND: Self-reported outcome measures are increasingly being collected for healthcare evaluation therefore it is prudent to understand their associations with patient outcomes. Our aims were to investigate: (1) if Oxford Knee Score (OKS) is associated with impending revision at long-term (5 and 10 years) follow-up, and (2) if decreased OKS at subsequent follow-ups is associated with higher risk of revision. PATIENTS AND METHODS: All total knee (TKAs) and unicompartmental knee arthroplasties (UKAs) between 1999 and 2019 in the New Zealand Joint Registry with an OKS at 6 months (TKA n = 27 708, UKA n = 8415), 5 years (TKA n = 11 519, UKA n = 3365) or 10 years (TKA n = 6311, UKA n = 1744) were included. Logistic regression determined associations of the OKS with revision within 2 years of each score. Change in OKS between timepoints were compared with revision risk. RESULTS: For every one-unit increase in OKS, the odds of TKA and UKA revision decreased by 10% and 11% at 6 months, 10% and 12% at 5 years and 9% and 5% at 10 years. For both procedures a decrease of seven or more OKS points from previous follow-up was associated with higher risk of revision (5 years: TKA 4.7% versus 0.5%, UKA 8.7% versus 0.9%; 10 years: TKA 4.4% versus 0.7%, UKA 11.3% versus 1.5%; all P < 0.01). CONCLUSION: The OKS had a strong negative association with risk of impending TKA and UKA revision from early to long-term (10+ years) follow-up. A decrease of seven or more points when compared with the previous follow-up was also associated with higher revision risk.

Enhanced bone formation in locally-optimised, low-stiffness additive manufactured titanium implants: An in silico and in vivo tibial advancement study.

A tibial tuberosity advancement (TTA), used to treat lameness in the canine stifle, provides a framework to investigate implant performance within an uneven loading environment due to the dominating patellar tendon. The purpose of this study was to reassess how we design orthopaedic implants in a load-bearing model to investigate potential for improved osseointegration capacity of fully-scaffolded mechanically-matched additive manufactured (AM) implants. While the mechanobiological nature of bone is well known, we have identified a lower limit in the literature where investigation into exceedingly soft scaffolds relative to trabecular bone ceases due to the trade-off in mechanical strength. We developed a finite element model of the sheep stifle to assess the stresses and strains of homogeneous and locally-optimised TTA implant designs. Using additive manufacturing, we printed three different low-stiffness Ti-6Al-4 V TTA implants: 0.8 GPa (Ti1), 0.6 GPa (Ti2) and an optimised design with a 0.3 GPa cortex and 0.1 GPa centre (Ti3), for implantation in a 12-week in vivo ovine pilot study. Static histomorphometry demonstrated uniform bone ingrowth in optimised low-modulus Ti3 samples compared to homogeneous designs (Ti1 and Ti2), and greater bone-implant contact. Mineralising surfaces were apparent in all implants, though mineral apposition rate was only consistent throughout Ti3. The greatest bone formation scores were seen in Ti3, followed by Ti2 and Ti1. Results from our study suggest lower stiffnesses and higher strain ranges improve early bone formation, and that by accounting for loading environments through rational design, implants can be optimised to improve uniform osseointegration. STATEMENT OF SIGNIFICANCE: The effect of different strain ranges on bone healing has been traditionally investigated and characterised through computational models, with much of the literature suggesting higher strain ranges being favourable. However, little has been done to incorporate strain-optimisation into porous orthopaedic implants due to the trade-off in mechanical strength required to induce these microenvironments. In this study, we used finite element analysis to optimise the design of additive manufactured (AM) titanium orthopaedic implants for different strain ranges, using a clinically-relevant surgical model. Our research suggests that there is potential for locally-optimised AM scaffolds in the use of orthopaedic devices to induce higher strains, which in turn encourages de novo bone formation and uniform osseointegration.

The lifetime revision risk of unicompartmental knee arthroplasty.

AIMS: Unicompartmental knee arthroplasty (UKA) has a higher risk of revision than total knee arthroplasty (TKA), particularly for younger patients. The outcome of knee arthroplasty is typically defined as implant survival or revision incidence after a defined number of years. This can be difficult for patients to conceptualize. We aimed to calculate the 'lifetime risk' of revision for UKA as a more meaningful estimate of risk projection over a patient's remaining lifetime, and to compare this to TKA. METHODS: Incidence of revision and mortality for all primary UKAs performed from 1999 to 2019 (n = 13,481) was obtained from the New Zealand Joint Registry (NZJR). Lifetime risk of revision was calculated for patients and stratified by age, sex, and American Society of Anesthesiologists (ASA) grade. RESULTS: The lifetime risk of revision was highest in the youngest age group (46 to 50 years; 40.4%) and decreased sequentially to the oldest (86 to 90 years; 3.7%). Across all age groups, lifetime risk of revision was higher for females (ranging from 4.3% to 43.4% vs males 2.9% to 37.4%) and patients with a higher ASA grade (ASA 3 to 4, ranging from 8.8% to 41.2% vs ASA 1 1.8% to 29.8%). The lifetime risk of revision for UKA was double that of TKA across all age groups (ranging from 3.7% to 40.4% for UKA, and 1.6% to 22.4% for TKA). The higher risk of revision in younger patients was associated with aseptic loosening in both sexes and pain in females. Periprosthetic joint infection (PJI) accounted for 4% of all UKA revisions, in contrast with 27% for TKA; the risk of PJI was higher for males than females for both procedures. CONCLUSION: Lifetime risk of revision may be a more meaningful measure of arthroplasty outcomes than implant survival at defined time periods. This study highlights the higher lifetime risk of UKA revision for younger patients, females, and those with a higher ASA grade, which can aid with patient counselling prior to UKA. Cite this article: Bone Joint J 2022;104-B(6):672-679.

3D bioassembly of cell-instructive chondrogenic and osteogenic hydrogel microspheres containing allogeneic stem cells for hybrid biofabrication of osteochondral constructs.

Recently developed modular bioassembly techniques hold tremendous potential in tissue engineering and regenerative medicine, due to their ability to recreate the complex microarchitecture of native tissue. Here, we developed a novel approach to fabricate hybrid tissue-engineered constructs adopting high-throughput microfluidic and 3D bioassembly strategies. Osteochondral tissue fabrication was adopted as an example in this study, because of the challenges in fabricating load bearing osteochondral tissue constructs with phenotypically distinct zonal architecture. By developing cell-instructive chondrogenic and osteogenic bioink microsphere modules in high-throughput, together with precise manipulation of the 3D bioassembly process, we successfully fabricated hybrid engineered osteochondral tissuein vitrowith integrated but distinct cartilage and bone layers. Furthermore, by encapsulating allogeneic umbilical cord blood-derived mesenchymal stromal cells, and demonstrating chondrogenic and osteogenic differentiation, the hybrid biofabrication of hydrogel microspheres in this 3D bioassembly model offers potential for an off-the-shelf, single-surgery strategy for osteochondral tissue repair.

Hybrid fabrication of photo-clickable vascular hydrogels with additive manufactured titanium implants for enhanced osseointegration and vascularized bone formation.

Bone regeneration of critical-sized bone defects, bone fractures or joint replacements remains a significant clinical challenge. Although there has been rapid advancement in both the fields of bone tissue engineering and additive manufacturing, functional bone implants with rapid vascularization capacity to ensure osseointegration and long-term biological fixation in large bone defects remains limited in clinics. In this study, we developed anin vitrovascularized bone implant by combining cell-laden hydrogels with direct metal printed (DMP) porous titanium alloys (Ti-6Al-4V). A 5 wt% allylated gelatin (GelAGE), was utilized to co-encapsulate human mesenchymal stromal cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) to investigate concurrent osteogenic and vasculogenic performance. DMP macro-porous Ti-6Al-4V scaffolds were subsequently infused/enriched with cell-laden GelAGE to examine the feasibility to deliver cells and engineer vascular-like networks in the hybrid implant. Furthermore, as a proof of concept, a full-scale porous Ti-6Al-4V acetabular cup was impregnated with cell-laden hydrogel to validate the clinical potential of this strategy. The vasculogenic potential was evaluated by examining micro-capillary formation coupled with capillary network maturation and stabilization. Osteogenic differentiation was assessed via alkaline phosphatase activity as well as osteocalcin and osteopontin expression. Our results suggested that GelAGE supported HUVECs spreading and vascular-like network formation, along with osteogenesis of hMSCs. Titanium hybrid constructs with cell-laden hydrogel demonstrated enhanced osteogenesis with similar vasculogenic capability compared to the cell-laden hydrogel alone constructs. The full-scale implant with cell-laden hydrogel coating similarly showed cell distribution and spreading, implying the potential for further clinical application. Our study presents the feasibility of integrating bio-functional hydrogels with porous titanium implants to fabricate a vascularized hybrid construct with both mechanical support and preferable biological functionality (osteogenesis/vasculogenesis), which paves the way for improved strategies to enhance bone regeneration in complex large bone defects achieving long-term bone-implant fixation.

The lifetime risk of revision following total knee arthroplasty : a New Zealand Joint Registry study.

AIMS: The success of total knee arthroplasty (TKA) is usually measured using functional outcome scores and revision-free survivorship. However, reporting the lifetime risk of revision may be more meaningful to patients when gauging risks, especially in younger patients. We aimed to assess the lifetime risk of revision for patients in different age categories at the time of undergoing primary TKA. METHODS: The New Zealand Joint Registry database was used to obtain revision rates, mortality, and the indications for revision for all primary TKAs performed during an 18-year period between January 1999 and December 2016. Patients were stratified into age groups at the time of the initial TKA, and the lifetime risk of revision was calculated according to age, sex, and the American Society of Anesthesiologists (ASA) grade. The most common indications for revision were also analyzed for each age group. RESULTS: The overall ten-year survival rate was 95.6%. This was lowest in the youngest age group (between 46 and 50 years) and increased sequentially with increasing age. The lifetime risk of requiring revision was 22.4% in those aged between 46 and 50 years at the time of the initial surgery, and decreased linearly with increasing age to 1.15% in those aged between 90 and 95 years at the time of surgery. Higher ASA grades were associated with increased lifetime risk of revision in all age groups. The three commonest indications for revision were aseptic loosening, infection, and unexplained pain. Young males, aged between 46 and 50 years, had the highest lifetime risk of revision (25.2%). CONCLUSION: Lifetime risk of revision may be a more meaningful measure of outcome than implant survival at defined time periods when counselling patients prior to TKA. This study highlights the considerably higher lifetime risk of revision surgery for all indications, including infection, in younger male patients. Cite this article: Bone Joint J 2022;104-B(2):235-241.

Ballistic trauma caused by military rifles: experimental study based on synthetic skull proxies.

Rifles are often involved in violent deaths such as homicide and suicide. Consequently, expert knowledge and experimental forensic investigations are important to clarify the nature of ballistic trauma when applied to the human head and neurocranium. This study investigated differences in entrance wound morphology with Synbone® spheres which are described as being comparable to human flat bones. A series of ballistic experiments were conducted using two different rifle calibers (5.56 × 45 mm and 7.62 × 39 mm Full Metal Jacket (FMJ)). Synbone® spheres were used for close-range 0.3 m simulated executions as well as at 25 m and 35 m to simulate urban and military engagements. Results were compared with previously published experimental studies using similar military ammunition. In our study, entry wound morphology closely resembles real forensic cases compared to exit wound and overall shape morphology independently of the distance and the caliber. Circumferential delamination was clearly visible with full metal jacket (FMJ) rounds, yielding similar damage pattern morphology to the human crania. This study documented the presence of hydraulic burst or shock in all ten rounds from all three distances. Krönlein shots were also observed in some cases. Synbone® spheres constitute an acceptable synthetic surrogate for ballistic experiments. The present study offers new initial data on the behavior of Synbone® proxies in ballistic testing of military ammunitions; FMJ gunshot injuries to the human head, for distances that have not previously been published, suggesting that efficient tests can take place under these conditions. Further research on experimental ballistics with a larger number of controlled factors and multiple repetitions is recommended to verify the results of this pilot study before applied in forensic simulations.

Surgical Helmet Systems Are Associated With a Lower Rate of Prosthetic Joint Infection After Total Knee Arthroplasty: Combined Results From the New Zealand Joint Registry and Surgical Site Infection Improvement Programme.

BACKGROUND: This study aimed to identify the risk factors, in particular the use of surgical helmet systems (SHSs), for prosthetic joint infection (PJI) after total knee arthroplasty (TKA). Data recorded by the New Zealand Surgical Site Infection Improvement Programme (SSIIP) and the New Zealand Joint Registry (NZJR) were combined and analyzed. METHODS: Primary TKA procedures performed between July 2013 and June 2018 that were recorded by both the SSIIP and NZJR were analyzed. Two primary outcomes were measured: (1) PJI within 90 days as recorded by the SSIIP and (2) revision TKA for deep infection within 6 months as recorded by the NZJR. Univariate and multivariate analyses were performed to identify risk factors for both outcomes with results considered significant at P < .05. RESULTS: A total of 19,322 primary TKAs were recorded by both databases in which 97 patients had a PJI within 90 days as recorded by the SSIIP (0.50%), and 90 patients had a revision TKA for deep infection within 6 months (0.47%) as recorded by the NZJR. An SHS was associated with a lower rate of PJI (adjusted odds ratio [OR] = 0.50, P = .008) and revision for deep infection (adjusted OR = 0.55, P = .022) than conventional gowning. Male sex (adjusted OR = 2.6, P < .001) and an American Society of Anesthesiologists score >2 were patient risk factors for infection (OR = 2.63, P < .001 for PJI and OR = 1.75, P = .017 for revision for deep infection). CONCLUSION: Using contemporary data from the SSIIP and NZJR, the use of the SHS was associated with a lower rate of PJI after primary TKA than conventional surgical gowning. Male sex and a higher American Society of Anesthesiologists score continue to be risk factors for infection.

How do 3D-printed primary uncemented acetabular components compare with established uncemented acetabular cups? The experience of the New Zealand National Joint Registry.

BACKGROUND: 3D-printed or additive manufactured acetabular implants are an exciting new technology being used in hip surgery with increasing frequency especially in complex acetabular reconstructions. However, the performance of acetabular components produced by this method for primary THR is unknown. METHODS: 41,272 uncemented cups in primary THR for OA were identified in the NZJR for the purposed of this study. There were 39,080 uncemented cups in the control group (15,798 Pinnacle cups, 12,724 Trident cups and 10,558 RM Pressfit cups) compared to 2192 3D-printed uncemented implants (1397 Delta TT cups, 640 Ti Por and 155 Polymax cups). All-cause revision rates and reasons for revision were examined. Kaplan-Meier survival analysis was performed. RESULTS: 3D-printed cups were inserted into younger, fitter patients with a higher mean BMI compared to those in the control group (p < 0.001). The overall all-cause revision rate for 3D-printed cups was not significantly different to the controls: 0.77/100 cys (95% CI 0.59-1) compared to 0.55/100 cys (95% CI 0.52-0.58) in the control group (p = 0.058, Hazards ratio 1.29, 95% CI 0.992-1.678). There was no difference in aseptic cup loosening or deep infection rates between either group or indeed individual implant designs. CONCLUSIONS: 3D-printed uncemented cups provide reliable survivorship and clinical results in primary THR comparable to established designs manufactured by traditional means. The theoretical concerns of increased rates of fatigue failure or deep infection are unsubstantiated.

Hybrid biofabrication of 3D osteoconductive constructs comprising Mg-based nanocomposites and cell-laden bioinks for bone repair.

Tissue engineering approaches for bone repair have rapidly evolved due to the development of novel biofabrication technologies, providing an opportunity to fabricate anatomically-accurate living implants with precise placement of specific cell types. However, limited availability of biomaterial inks, that can be 3D-printed with high resolution, while providing high structural support and the potential to direct cell differentiation and maturation towards the osteogenic phenotype, remains an ongoing challenge. Aiming towards a multifunctional biomaterial ink with high physical stability and biological functionality, this work describes the development of a nanocomposite biomaterial ink (Mg-PCL) comprising of magnesium hydroxide nanoparticles (Mg) and polycaprolactone (PCL) thermoplastic for 3D printing of strong and bioactive bone regenerative scaffolds. We characterised the Mg nanoparticle system and systematically investigated the cytotoxic and osteogenic effects of Mg supplementation to human mesenchymal stromal cells (hMSCs) 2D-cultures. Next, we prepared Mg-PCL biomaterial ink using a solvent casting method, and studied the effect of Mg over mechanical properties, printability and scaffold degradation. Furthermore, we delivered MSCs within Mg-PCL scaffolds using a gelatin-methacryloyl (GelMA) matrix, and evaluated the effect of Mg over cell viability and osteogenic differentiation. Nanocomposite Mg-PCL could be printed with high fidelity at 20 wt% of Mg content, and generated a mechanical reinforcement between 30%-400% depending on the construct internal geometry. We show that Mg-PCL degrades faster than standard PCL in an accelerated-degradation assay, which has positive implications towards in vivo implant degradation and bone regeneration. Mg-PCL did not affect MSCs viability, but enhanced osteogenic differentiation and bone-specific matrix deposition, as demonstrated by higher ALP/DNA levels and Alizarin Red calcium staining. Finally, we present proof of concept of Mg-PCL being utilised in combination with a bone-specific bioink (Sr-GelMA) in a coordinated-extrusion bioprinting strategy for fabrication of hybrid constructs with high stability and synergistic biological functionality. Mg-PCL further enhanced the osteogenic differentiation of encapsulated MSCs and supported bone ECM deposition within the bioink component of the hybrid construct, evidenced by mineralised nodule formation, osteocalcin (OCN) and collagen type-I (Col I) expression within the bioink filaments. This study demonstrated that magnesium-based nanocomposite bioink material optimised for extrusion-based 3D printing of bone regenerative scaffolds provide enhanced mechanical stability and bone-related bioactivity with promising potential for skeletal tissue regeneration.

Probing Multicellular Tissue Fusion of Cocultured Spheroids-A 3D-Bioassembly Model.

While decades of research have enriched the knowledge of how to grow cells into mature tissues, little is yet known about the next phase: fusing of these engineered tissues into larger functional structures. The specific effect of multicellular interfaces on tissue fusion remains largely unexplored. Here, a facile 3D-bioassembly platform is introduced to primarily study fusion of cartilage-cartilage interfaces using spheroids formed from human mesenchymal stromal cells (hMSCs) and articular chondrocytes (hACs). 3D-bioassembly of two adjacent hMSCs spheroids displays coordinated migration and noteworthy matrix deposition while the interface between two hAC tissues lacks both cells and type-II collagen. Cocultures contribute to increased phenotypic stability in the fusion region while close initial contact between hMSCs and hACs (mixed) yields superior hyaline differentiation over more distant, indirect cocultures. This reduced ability of potent hMSCs to fuse with mature hAC tissue further underlines the major clinical challenge that is integration. Together, this data offer the first proof of an in vitro 3D-model to reliably study lateral fusion mechanisms between multicellular spheroids and mature cartilage tissues. Ultimately, this high-throughput 3D-bioassembly model provides a bridge between understanding cellular differentiation and tissue fusion and offers the potential to probe fundamental biological mechanisms that underpin organogenesis.

Allogeneic mesenchymal stromal cells for cartilage regeneration: A review of in vitro evaluation, clinical experience, and translational opportunities.

The paracrine signaling, immunogenic properties and possible applications of mesenchymal stromal cells (MSCs) for cartilage tissue engineering and regenerative medicine therapies have been investigated through numerous in vitro, animal model and clinical studies. The emerging knowledge largely supports the concept of MSCs as signaling and modulatory cells, exerting their influence through trophic and immune mediation rather than as a cell replacement therapy. The virtues of allogeneic cells as a ready-to-use product with well-defined characteristics of cell surface marker expression, proliferative ability, and differentiation capacity are well established. With clinical applications in mind, a greater focus on allogeneic cell sources is evident, and this review summarizes the latest published and upcoming clinical trials focused on cartilage regeneration adopting allogeneic and autologous cell sources. Moreover, we review the current understanding of immune modulatory mechanisms and the role of trophic factors in articular chondrocyte-MSC interactions that offer feasible targets for evaluating MSC activity in vivo within the intra-articular environment. Furthermore, bringing labeling and tracking techniques to the clinical setting, while inherently challenging, will be extremely informative as clinicians and researchers seek to bolster the case for the safety and efficacy of allogeneic MSCs. We therefore review multiple promising approaches for cell tracking and labeling, including both chimerism studies and imaging-based techniques, that have been widely explored in vitro and in animal models. Understanding the distribution and persistence of transplanted MSCs is necessary to fully realize their potential in cartilage regeneration techniques and tissue engineering applications.

Strategies for inclusion of growth factors into 3D printed bone grafts.

There remains a critical need to develop new technologies and materials that can meet the demands of treating large bone defects. The advancement of 3-dimensional (3D) printing technologies has allowed the creation of personalized and customized bone grafts, with specific control in both macro- and micro-architecture, and desired mechanical properties. Nevertheless, the biomaterials used for the production of these bone grafts often possess poor biological properties. The incorporation of growth factors (GFs), which are the natural orchestrators of the physiological healing process, into 3D printed bone grafts, represents a promising strategy to achieve the bioactivity required to enhance bone regeneration. In this review, the possible strategies used to incorporate GFs to 3D printed constructs are presented with a specific focus on bone regeneration. In particular, the strengths and limitations of different methods, such as physical and chemical cross-linking, which are currently used to incorporate GFs to the engineered constructs are critically reviewed. Different strategies used to present one or more GFs to achieve simultaneous angiogenesis and vasculogenesis for enhanced bone regeneration are also covered in this review. In addition, the possibility of combining several manufacturing approaches to fabricate hybrid constructs, which better mimic the complexity of biological niches, is presented. Finally, the clinical relevance of these approaches and the future steps that should be taken are discussed.

Converging functionality: Strategies for 3D hybrid-construct biofabrication and the role of composite biomaterials for skeletal regeneration.

The evolution of additive manufacturing (AM) technologies, biomaterial development and our increasing understanding of cell biology has created enormous potential for the development of personalized regenerative therapies. In the context of skeletal tissue engineering, physical and biological demands play key roles towards successful construct implantation and the achievement of bone, cartilage and blood vessel tissue formation. Nevertheless, meeting such physical and biological demands to mimic the complexity of human tissues and their functionality is still a significant ongoing challenge. Recent studies have demonstrated that combination of AM technologies and advanced biomaterials has great potential towards skeletal tissue engineering. This review aims to analyze how the most prominent technologies and discoveries in the field converge towards the development of advanced constructs for skeletal regeneration. Particular attention is placed on hybrid biofabrication strategies, combining bioinks for cell delivery with biomaterial inks providing physical support. Hybrid biofabrication has been the focus of recent emerging strategies, however there has been limited review and analysis of these techniques and the challenges involved. Furthermore, we have identified that there are multiple hybrid fabrication strategies, here we present a category system where each strategy is reviewed highlighting their distinct advantages, challenges and potential applications. In addition, bioinks and biomaterial inks are the main components of the hybrid biofabrication strategies, where it is recognized that such platforms still lack optimal physical and biological functionality. Thus, this review also explores the development of composite materials specifically targeting the enhancement of physical and biological functionality towards improved skeletal tissue engineering. STATEMENT OF SIGNIFICANCE: Biofabrication strategies capable of recreating the complexity of native tissues could open new clinical possibilities towards patient-specific regenerative therapies and disease models. Several reviews target the existing additive manufacturing (AM) technologies that may be utilised for biomedical purposes. However, this work presents a unique perspective, describing how such AM technologies have been recently translated towards hybrid fabrication strategies, targeting the fabrication of constructs with converging physical and biological properties. Furthermore, we address composite bioinks and biomaterial inks that have been engineered to overcome traditional limitations, and might be applied to the hybrid fabrication strategies outlined. This work offers ample perspectives and insights into the current and future challenges for the fabrication of skeletal tissues aiming towards clinical and biomedical applications.

The lifetime risk of revision following total hip arthroplasty.

AIMS: Joint registries typically use revision of an implant as an endpoint and report survival rates after a defined number of years. However, reporting lifetime risk of revision may be more meaningful, especially in younger patients. We aimed to assess lifetime risk of revision for patients in defined age groups at the time of primary surgery. METHODS: The New Zealand Joint Registry (NZJR) was used to obtain rates and causes of revision for all primary total hip arthroplasties (THAs) performed between January 1999 and December 2016. The NZJR is linked to the New Zealand Registry of Births, Deaths and Marriages to obtain complete and accurate data. Patients were stratified by age at primary surgery, and lifetime risk of revision calculated according to age, sex, and American Society of Anesthesiologists (ASA) classification. The most common causes for revision were also analyzed for each age group. RESULTS: The overall, ten-year implant survival rate was 93.6% (95% confidence interval (CI) 93.4% to 93.8%). It was lowest in the youngest age group (46 to 50 years), rising sequentially with increasing age to 97.5% in the oldest group (90 to 95 years). Lifetime risk of revision surgery was 27.6% (95% CI 27.3% to 27.8%) in those aged 46 to 50 years, decreasing with age to 1.1% (95% CI 0.0% to 5.8%) in those aged 90 to 95 years at the time of primary surgery. Higher ASA grades were associated with an increased lifetime risk of revision across all ages. The commonest causes for revision THA were aseptic loosening, infection, periprosthetic fracture, and dislocation. CONCLUSION: When counselling patients preoperatively, the lifetime risk of revision may be a more meaningful and useful measure of longer-term outcome than implant survival at defined time periods. This study highlights the considerably increased likelihood of subsequent revision surgery in younger age groups. Cite this article: Bone Joint J 2021;103-B(3):479-485.