Functionally Tailored Metal-Organic Framework Coatings for Mediating Ti Implant Osseointegration.

Owing to their mechanical resilience and non-toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone fractures. However, the intrinsic bioinertness of Ti and its alloys often impedes the effective osseointegration of the implants, leading to severe adverse complications including implant loosening, detachment, and secondary bone damage. Consequently, new Ti implant engineering strategies are urgently needed to improve their osseointegration after implantation. Remarkably, metalorganic frameworks (MOFs) are a class of novel synthetic material consisting of coordinated metal species and organic ligands, which have demonstrated a plethora of favorable properties for modulating the interfacial properties of Ti implants. This review comprehensively summarizes the recent progress in the development of MOF-coated Ti implants and highlights their potential utility for modulating the bio-implant interface to improve implant osseointegration, of which the discussions are outlined according to their physical traits, chemical composition, and drug delivery capacity. A perspective is also provided in this review regarding the current limitations and future opportunities of MOF-coated Ti implants for orthopedic applications. The insights in this review may facilitate the rational design of more advanced Ti implants with enhanced therapeutic performance and safety.

Sustained and Targeted Delivery of Self-Assembled Doxorubicin Nonapeptides Using pH-Responsive Hydrogels for Osteosarcoma Chemotherapy.

While chemotherapeutic agents have particularly potent effects in many types of cancer, their clinical applications are still far from satisfactory due to off-target drug exposure, chemotherapy resistance, and adverse effects, especially in osteosarcoma. Therefore, it is clinically promising to construct a novel tumor-targeted drug delivery system to control drug release and alleviate side effects. In this study, a pH-responsive nonapeptide hydrogel was designed and fabricated for the tumor-targeted drug delivery of doxorubicin (DOX). Using a solid-phase synthesis method, a nonapeptide named P1 peptide that is structurally akin to surfactant-like peptides (SLPs) due to its hydrophobic tail and hydrophilic head was synthesized. The physicochemical properties of the P1 hydrogel were characterized via encapsulation capacity, transmission electron microscopy (TEM), circular dichroism (CD), zeta potential, rheological analysis, and drug release studies. We also used in vitro and in vivo experiments to investigate the cytocompatibility and tumor inhibitory efficacy of the drug-loaded peptide hydrogel. The P1 peptide could self-assemble into biodegradable hydrogels under neutral conditions, and the prepared drug-loaded hydrogels exhibited good injectability and biocompatibility. The in vitro drug release studies showed that DOX-P1 hydrogels had high sensitivity to acidic conditions (pH 5.8 versus 7.4, up to 3.6-fold). Furthermore, the in vivo experiments demonstrated that the DOX-P1 hydrogel could not only amplify the therapeutic effect but also increase DOX accumulation at the tumor site. Our study proposes a promising approach to designing a pH-responsive hydrogel with controlled doxorubicin-release action based on self-assembled nonapeptides for targeted chemotherapy.

Robot-assisted surgery in total knee arthroplasty: trauma maker or trauma savior? A prospective, randomized cohort study.

Background: Robotic assistance has been increasingly employed to improve the operative precision in modern knee surgery. The purpose of the study was to evaluate the trauma effect of one of the first domestically developed orthopedic surgical robots in China in a clinical trial of robot-assisted total knee arthroplasty (RA-TKA). Methods: A total of 33 patients who underwent unilateral TKA for end-stage osteoarthritis were randomized to receive RA-TKA (17 cases) or conventional manual TKA (CM-TKA) in our institution in 2020. The trauma effects of the 4 main indicators with 48 sub-indicators in terms of subsectional operative time, inflammation and coagulation markers, physical and radiographical analyses of osteotomy deviation, and postoperative comfort were analyzed. Results: Subsectional operative time analysis showed that the times for bone cutting and gap balancing with RA-TKA were 5.3 and 2.2 min shorter than those with CM-TKA (p = 0.010, p = 0.02), respectively. Arterial blood gas indicators (partial pressure of carbon dioxide, partial pressure of oxygen and SO2) 24 h after RA-TKA, as well as the white blood cell count and neutrophil ratio, were significantly lower than those after CM-TKA (p < 0.05). Inflammatory markers at 72 h after surgery showed the increments of C-reactive protein, erythrocyte sedimentation rate and D-dimer of RA-TKA declined by 180.7, 22.0 and 1050.0% (p < 0.05), respectively, referenced to the preoperative baseline values, as compared to CM-TKA. Mechanical deviation distribution exhibited percentages of region I errors for RA-TKA and CM-TKA of 76.5% and 27.1% (p = 0.000), respectively, and the success rates of one-time osteotomy were 94.1% and 62.5% (p = 0.039), respectively. Radiographical verification showed RA-TKA was more conducive to achieving mechanical alignment and ideal tibial component azimuths. Postoperative efficacy showed that patients were more comfortable after RA-TKA in terms of reduced administration of tranexamic acid, hydrocortisone and the utilization rate of temporary intensive opioid analgesics. No statistical difference in patient-reported outcome measures and complications were recorded between the two groups during continuous observation. Conclusions: Compared with CM-TKA, RA-TKA decreases rather than increases trauma. It might shorten the time required for bone cutting and gap balancing, reduce mechanical errors related to the osteotomy and prosthesis position, and improve the accuracy of the mechanical alignment reconstruction. RA-TKA is also favorable in promoting postoperative comfort and minimizing inflammatory response and drug consumption. Trial registration: The Chinese Clinical Trial Registry (ChiCTR2000031282) approved registration on 26 March 2020.

A New Recombinant Fibronectin/Cadherin Protein-Hydrophobically Modified Glycol Chitosan/Paclitaxel Layer-By-Layer Self-Assembly Strategy for the Postoperative Therapy of Osteosarcoma and Correlated Bone Injury.

Osteosarcoma is one of the most aggressive cancers which greatly threatens the health of adolescents and surgery is difficult to resect the whole piece of tumor tissue. The residual tumor cells might proliferate at the tumor site and invade into the blood circulation, leading to tumor recurrence and metastasis. Besides, the invasion of tumor cells could also lead to bone injury. We designed a recombinant fibronectin-cadherin fusion protein/hydrophobically modified glycol chitosan-PTX nanoparticles (rFN-CDH/HGC-PTX) layer-by-layer self-assembly polymer based on biphasic calcium phosphate ceramic (BCP) (BCP-PEI-(rFN/CDH-PTX/HGC)n-rFN/CDH). The SEM, FTIR, XPS and contact angle experiments proved the successful synthesis of the polymer. The chemotherapy drug PTX and bone-repairing-related rFN/CDH fusion protein could be stably released within one week and the in vitro experiments exhibited the efficacy of the polymer to kill residual tumor cells and promote the proliferation of osteoblast, confirming that our polymer was a superior material for postoperative osteosarcoma therapy.

Predictive factors associated with the clinical outcome of intertrochanteric hip fracture in high-risk elderly patients treated with total hip arthroplasty versus percutaneous external fixation.

BACKGROUND: Little is known regarding the survival and functional recovery of elderly intertrochanteric hip fracture (IHF) patients after total hip arthroplasty (THA) versus percutaneous external fixation (PEF). This study aims to analyze the prognostic factors of THA and PEF in elderly IHF patients. METHODS: A total of 155 consecutive elderly patients (mean age of 80 years) diagnosed with IHF were retrospectively reviewed from our database between January 1, 2010, and December 31, 2018. The preoperative, intraoperative and postoperative covariates were analyzed by two independent surgical cohorts: THA and PEF. The main outcomes included the hip function score, all-cause mortality within 1 year after surgery, and overall survival. Covariables and their influence on independent outcomes were analyzed using multivariate regression models. RESULTS: The median follow-up period was 5.1 years, and 6 patients were lost to follow-up. At the endpoint, 70 of 85 patients treated with THA and 37 of 70 patients treated with PEF survived, exhibiting mean Harris hip scores of 84.4 and 69.0, respectively. The Kaplan-Meier curves and log-rank tests showed no significant difference in overall survival. After adjusting for the covariates, the surgical mode was a unique prognostic factor affecting hip function recovery, and two prognostic factors (leukocyte count and D-dimer) were correlated with 1-year all-cause mortality. Age at admission, fracture classification, D-dimer level and surgical mode were identified as prognostic factors affecting overall survival. After adjusting for the former three covariates, THA reduced the risk of death by 67.20% compared with PEF (HR 0.328, 95% CI, 0.121-0.890). CONCLUSIONS: Despite the nonsignificant difference in 1-year all-cause mortality, THA demonstrated superior midterm survival and hip function recovery in elderly IHF patients compared with PEF. Predictive factors, including age at admission, fracture classification, D-dimer level and surgical mode, are associated with the overall survival of IHF in high-risk elderly patients.

Clinical evaluation of direct anterior approach total hip arthroplasty for severe developmental dysplasia of the hip.

It is challenging to treat developmental dysplasia of the hip (DDH) classified Crowe III-IV using direct anterior approach (DAA) total hip arthroplasty (THA), and very little is known on its outcome. This study aimed to investigate the clinical result in this defined disorder with DAA versus posterolateral approach. Twenty-three consecutive hips with Crowe III-IV DDH who underwent DAA were retrospectively evaluated from 2016 through 2018. Outcomes were primarily assessed by HHS, WOMAC, and SF-12 physical scales. The second evaluations included leg length discrepancy, hip muscle strength, radiographic review, complications, and limp recovery. Results were compared to a control cohort of 50 hips underwent posterolateral THA concurrently within the observational period. At last follow-up (DAA 28.5 months; PLA 39.0 months), the mean increase of the HHS for DAA was 48.2 and 30.3 for PLA (p = 0.003). The improvement in WOMAC score in DAA cohort was 15.89 higher that of the PLA cohort after adjusting preoperative difference [R2 = 0.532, P = 0.000, 95% CI (10.037, 21.735)]. DAA had more rapid recovery of hip abductor strength at 1-month (p = 0.03) and hip flexor strength at 3 months (p = 0.007) compared to PLA. No significant differences were found in the radiographic analysis with the exception of increased acetabular anteversion in the DAA cohort (p = 0.036). Satisfactory improvement in limp, indicated by the percentage of limp graded as none and mild to the total, was much higher in DAA cohort (97.6%), compared to that of PLA cohort (90.0%, p = 0.032). DAA for high-dislocated dysplasia demonstrate a significant improvement in clinical result comparable to posterolateral approach. Improved clinical outcome in terms of increased HHS and WOMAC scores, rapid recovery of hip abductor and flexor strength, and enhanced limp recovery without an increased risk in complications, could be acquired when the surgeons were specialized in this approach.

Subtrochanteric Osteotomy in Direct Anterior Approach Total Hip Arthroplasty.

Subtrochanteric osteotomy of the femur (STO) is a valuable corrective procedure in hip surgeries. However, STO in traditional posterolateral approach usually encounters complications such as postoperative dislocation, bone non-union, and prosthesis failure. Some relevant pathologies and mechanisms have been identified, but there is sparse evidence for verification. The aim of this video in orthopaedic technique is to test our hypothesis of STO in direct anterior approach to total hip arthroplasty in a complicated hip surgery, and to further illustrate the rationality, reproducibility, and superiority of STO in this minimally invasive and enhanced-recovery approach by presenting a standardized and systemic protocol, as well as operational pearls and pitfalls.

Direct Anterior Approach in Crowe Type III-IV Developmental Dysplasia of the Hip: Surgical Technique and 2 years Follow-up from Southwest China.

OBJECTIVES: To summarize our pioneering surgical practice and clinical outcome of Crowe type III-IV developmental dysplasia of the hip (DDH) with a direct anterior approach total hip arthroplasty in a single teaching hospital in Southwest China. METHODS: Fourteen patients (15 hips) diagnosed with Crowe type III-IV developmental dysplasia of the hip were involved in this single-center retrospective study between 2016 and 2018. A comprehensive surgical procedure, including preoperative planning and algorithms for leg length equalization, intraoperative stepwise soft tissue release, bone defect reconstruction, and an innovative subtrochanteric osteotomy, was described. Furthermore, advancements in intraoperative CT guidance, computer navigation, and nerve monitoring were available for specific demands. The short-term clinical outcome was evaluated at the endpoint of follow-up by three patient-reported functional scales (Harris, WOMAC, and SF-12 scores), and objective data collected at the clinic, including functional recovery (muscle strength of hip flexor and abductor, correction of the pelvic tilt, leg length discrepancy, and limp), radiographic analysis, and complication occurrence. RESULTS: The intraoperative variables were carefully recorded. The mean operating times in Crowe type III and IV groups were 115.8 min and 156.2 min, and the median blood loss volumes were 520.5 mL and 810.2 mL, respectively. The general changes in the Harris, SF-12, and WOMAC scores of the two groups were 46.2, 8.7 and 134.3, respectively, at a mean follow-up of 25.4 months. Enhanced recovery of hip abductor muscle strength was identified in 85.7% of the population at the third postoperative month. The equalization of leg length and correction of the pelvic tile were observed at the sixth postoperative month, with a 36-mm decrease in leg length discrepancy. No radiographic evidence of the loosening or migration of the components was observed. A self-innovated subtrochanteric shortening osteotomy was performed in five patients, and they healed after 6 months. Specific complications included two cases of distal femoral cracks and one case of a periprosthetic fracture needing internal fixation. Two patients received a late iliotibial band release at the 3rd month postoperatively due to progressive genu valgum. No records of infection, dislocation, nerve palsy, bone non-union, or revision surgery were identified. DISCUSSION: The direct anterior approach total hip arthroplasty showed potential advantages, including optimum component positioning, improved hip stability, steerable complication rate, and enhanced functional recovery with Crowe type III-IV DDH. The short-term outcome is comparable to that of the traditional posterolateral approach.

Direct anterior approach total hip arthroplasty for Crowe III and IV dysplasia.

High-dislocated hip dysplasia is challenging to treat with total hip arthroplasty via the direct anterior approach (DAA). The DAA has potential advantages including optimizing component positioning, enhanced hip stability, and a more rapid postoperative recovery. We present a surgical technique for DAA total hip arthroplasty for hip dysplasia that includes preoperative planning, soft tissue releases, subtrochanteric osteotomy, component placement, and intraoperative nerve monitoring and imaging. This technique provides detailed technical instructions, specifically including pearls and pitfalls, and complication prevention strategies.

Optimized clinical practice for superaged patients with hip fracture: significance of damage control and enhanced recovery program.

With the advent of global aging, the incidence, mortality, and medical costs of hip fracture among aged patients are increasing annually. The number of controlled clinical studies and health economics analyses that conform to evidence-based medicine principles is growing day by day. However, unfortunately, no specific recommendations regarding the procedures for the treatment of hip fracture are available. Meanwhile, the existence of both traditional treatment systems and new treatment theories means that most doctors confront difficult choices in their daily practice. These factors make the therapeutic approach for aged patients, especially among superaged patients with hip fracture, extremely challenging. This study focuses on superaged patients (> 80 years as defined by the World Health Organization) with hip fracture and includes their preoperative pathological condition; therapeutic decision-making in terms of the benefit and risk ratio, damage control theory, and enhanced recovery after surgery were also investigated. These patients were discussed specifically by combining the current treatment strategies from several experts and the results of a meta-analysis published recently. The study presents some new ideas and approaches currently recognized in the field, such as preoperative assessment, surgical planning, safety consideration, complication intervention, and enhanced recovery implementation, and further presents some clear interpretations regarding misunderstandings in clinical practice. Finally, optimized treatment according to damage control principles and enhanced recovery after surgery during the perioperative period among superaged hip fracture patients is defined.