A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model.

Regeneration of hyaline cartilage in human-sized joints remains a clinical challenge, and it is a critical unmet need that would contribute to longer healthspans. Injectable scaffolds for cartilage repair that integrate both bioactivity and sufficiently robust physical properties to withstand joint stresses offer a promising strategy. We report here on a hybrid biomaterial that combines a bioactive peptide amphiphile supramolecular polymer that specifically binds the chondrogenic cytokine transforming growth factor ß-1 (TGFß-1) and crosslinked hyaluronic acid microgels that drive formation of filament bundles, a hierarchical motif common in natural musculoskeletal tissues. The scaffold is an injectable slurry that generates a porous rubbery material when exposed to calcium ions once placed in cartilage defects. The hybrid material was found to support in vitro chondrogenic differentiation of encapsulated stem cells in response to sustained delivery of TGFß-1. Using a sheep model, we implanted the scaffold in shallow osteochondral defects and found it can remain localized in mechanically active joints. Evaluation of resected joints showed significantly improved repair of hyaline cartilage in osteochondral defects injected with the scaffold relative to defects injected with the growth factor alone, including implantation in the load-bearing femoral condyle. These results demonstrate the potential of the hybrid biomimetic scaffold as a niche to favor cartilage repair in mechanically active joints using a clinically relevant large-animal model.

How Strong Is the Ligamentum Teres of the Hip? A Biomechanical Analysis.

BACKGROUND: Intraarticular hip pain represents a substantial clinical challenge, with recent studies implicating lesions in the ligamentum teres as potential contributors. Even more so, damage to the ligamentum teres is particularly prevalent among young patients undergoing joint-preserving interventions. Although several studies have investigated the biomechanical attributes of the ligamentum teres, inconsistencies in reported findings and reliance on cadaveric or animal models have raised concerns regarding the extrapolation of results to clinical practice. Furthermore, there is a lack of research examining ligamentum teres biomechanics specifically within the relevant patient cohort-individuals who benefit from joint-preserving surgical interventions. QUESTIONS/PURPOSES: We sought (1) to determine the biomechanical properties (ultimate load to failure, tensile strength, stiffness, and elastic modulus) of fresh-frozen ligaments from patients undergoing surgical hip dislocation, and (2) to identify patient-specific factors that are associated with them. METHODS: This was an institutional review board-approved study on intraoperatively harvested ligamentum teres from 74 consecutive patients undergoing surgical hip dislocation for joint preservation (August 2021 to September 2022). After the exclusion of patients with previous surgery, posttraumatic deformities, avascular necrosis, slipped capital femoral epiphysis, and Perthes disease, 31 ligaments from 31 patients were analyzed. The mean age of the study group was 27 ± 8 years, and 61% (19) of participants were male. The main indication for surgery was femoroacetabular impingement. Standardized AP pelvic and axial radiographs and CT scans were performed in all patients for better radiological description of the population and to identify associated radiological factors. The ligament was thoroughly transected at its origin on the fossa acetabuli and at the insertion area on the fovea capitis and stored at -20°C until utilization. Specimens were mounted to a materials testing machine via custom clamps that minimized slippage and the likelihood of failure at the clamp. Force-displacement and stress-strain curves were generated. Ultimate failure load (N), tensile strength (MPa), stiffness (N/mm), and elastic modulus (MPa) were determined. Using a multivariate regression analysis and a subgroup analysis, we tested demographic, degenerative, and radiographic factors as potential associated factors. RESULTS: The ligamentum teres demonstrated an ultimate load to failure of 126 ± 92 N, and the tensile strength was 1 ± 1 MPa. The ligaments exhibited a stiffness of 24 ± 15 N/mm and an elastic modulus of 7 ± 5 MPa. After controlling for potential confounding variables like age, fossa/fovea degeneration, and acetabular/femoral morphologies, we found that female sex was an independent factor for higher tensile strength, stiffness, and elastic modulus. Excessive femoral version was independently associated with lower load to failure (HR 122 [95% CI 47 to 197]) and stiffness (HR 15 [95% CI 2 to 27]). Damage to the acetabular fossa was associated with reduced load to failure (HR -93 [95% CI -159 to -27]). CONCLUSION: Overall, the ligamentum teres is a relatively weak ligament. Sex, degeneration, and excessive femoral version are influencing factors on strength of the ligamentum teres. The ligamentum teres exhibits lower strength compared with other joint-stabilizing ligaments, which calls into question its overall contribution to hip stability. CLINICAL RELEVANCE: Young patients undergoing hip-preserving surgery are the population at risk for ligamentum teres lesions. Baseline values for load to failure, tensile strength, elastic modulus, and stiffness are needed to better understand those lesions in this cohort of interest.

Editorial Commentary: Iliotibial Band Autograft Is a Safe and Effective Technique for Hip Labral Reconstruction.

Hip labral reconstruction is indicated for hypoplastic, ossified, or irreparable labral tears in the primary and revision settings. Arthroscopic reconstruction for insufficient labral tissue requires advanced surgical techniques to restore hip biomechanics and re-establish the suction seal. With the growing number of arthroscopic hip procedures being performed, this is an increasingly familiar scenario. In our experience, the iliotibial band (ITB) autograft provides a safe and effective technique for labral reconstruction at 10-year clinical follow-up. Although the harvest requires an additional incision, the graft is incredibly versatile and can be harvested at any size to address the labral deficiency. Despite the concerns for donor-site morbidity, our extensive experience shows this is incredibly rare. In addition, concomitant pathology, such as greater trochanteric bursitis, can be addressed through this incision. Other grafts can be used for labral reconstruction, such as the indirect head of the rectus femoris tendon, but this is often limited to smaller labral defects less than 1 cm. ITB autograft shows excellent mid- to long-term outcomes, and second-look surgeries show excellent incorporation of the ITB autograft. And, in contrast to allograft, autograft tissue has demonstrated lower revision rates. The type of autograft used is per surgeon discretion based on experience and preference. In our hands, ITB is optimal due to proven effectiveness, durability, versatility, and limited donor-site morbidity.

Biomechanical Comparison Between Double-Row Repair and Soft Tissue Tenodesis for Treatment of Proximal Rectus Femoris Avulsions.

Background: Some patients with proximal rectus femoris (PRF) avulsions require surgical treatment after failed nonoperative treatment. There is no consensus on the superiority of suture anchor repair with the suture-bridge repair (SBR) technique versus tenodesis repair (TR) for PRF avulsions. Purpose: To compare the failure load and elongation at failure between SBR and TR and to compare the stiffness of these 2 repair techniques versus the native state. Study Design: Controlled laboratory study. Methods: Seven pairs of human cadaveric hemipelvises were dissected to the PRF and sartorius origins. Each specimen underwent preconditioning followed by a distraction test to determine the stiffness of the native specimen. One specimen of each pair received one of the repair methods (SBR or TR), while the other specimen in the pair received the other repair technique. After repair, each specimen underwent preconditioning followed by a pull to failure. The failure load, elongation at failure, stiffness, mode of failure, and stiffness as a percentage of the native state were determined for each repair. Results: The SBR group exhibited a stronger failure load (223 ± 51 N vs 153 ± 32 N for the TR group; P = .0116) and significantly higher stiffness as a percentage from the native state (70.4% ± 19% vs 33.8% ± 15.5% for the TR group; P = .0085). While the stiffness of the repair state in the SBR group (41.5 ± 9.4 N/mm) was not significantly different from that of the native state (66.2 ± 36 N/mm), the stiffness of the repair state in the TR group (20.3 ± 7.5 N/mm) was significantly lower compared with that of the native state (65.4 ± 22.1 N/mm; P < .001) and repair state in the SBR group (41.5 ± 9.4 N/mm; P = .02). The SBR group primarily failed at the repair site (71%), and the TR group primarily failed at the suture-sartorius interface (43%) and at the muscle (29%). Conclusion: SBR and TR specimens were significantly weaker than the native tendon. The stiffness of the SBR was equivalent to that of the native tendon, while TR was significantly less stiff than the native tendon. The SBR was superior to TR in terms of failure load, stiffness, and percentage stiffness from the native state. Clinical Relevance: SBR may be a better surgical option than TR to optimize failure load and stiffness for PRF avulsions.

Evaluating the Morphology of Unique Superficial Fissured Cartilage Lesions at the Femoral Head-Neck Junction in Patients with Femoroacetabular Impingement Syndrome.

Background: While an association between femoroacetabular impingement (FAI) and osteoarthritis (OA) has been reported, the mechanistic differences and transition between the 2 conditions is not fully understood. In FAI, cartilage lesions at the femoral head-neck junction can sometimes be visualized during hip arthroscopy. Purpose/Hypothesis: The purpose of this study was to describe a unique dimpled pattern of superficial fissured cartilage lesions on the femoral head-neck junction at impingement site in patients with FAI syndrome (FAIS) and to evaluate the clinical, histological, and genetic phenotype of this cartilage. We hypothesized that the cartilage lesions may indicate risk for, or predict occurrence of, OA. Study Design: Controlled laboratory study. Methods: Six hips (6 patients; mean age, 34.2 ± 12.9 years; range, 19-54 years) with dimpled or fissured cartilage were included among patients who underwent hip arthroscopy for treatment of FAIS from October 2020 through December 2021. This affected cartilage (dimple-pattern group) and normal cartilage (control group) on the femoral head-neck junction were collected from the same patients and evaluated for histological quantification by Mankin scores and expression of proteins related to cartilage degeneration (eg, matrix metalloproteinase [MMP]-1, MMP-2, MMP-3, MMP-10, and MMP-12, tissue inhibitor of metalloproteinase [TIMP]-1 and TMP-2, aggrecan neopepitope CS846, and hyaluronic acid [HA]) with the use of Milliplex Multiplex Assays. Results: All 6 hips were of the mixed FAI subtype. Preoperatively, 4 of 6 hips had Tönnis grade 1 radiographic changes, which was associated with greater femoral head chondral damage visualized intraoperatively. Mankin scores for the normal cartilage group and the dimple-pattern group were 0.67 ± 0.82 and 3.3 ± 0.82, respectively. Dimple pattern fissured cartilage showed a significant increase in Mankin score (P = .031) and a significant increase in protein expression of CS846 (P = .031) compared with normal cartilage. There were no significant differences in MMPs, TIMPs, or HA levels between the 2 groups. Conclusion: The dimple pattern fissured cartilage, compared to normal cartilage, showed histologically significant cartilage degeneration and a significant increase in protein expression of CS846, a biomarker for early OA. Clinical Relevance: This lesion serves as helpful visual indicator of early degeneration of the cartilage of femoral head-neck junction caused by FAIS.

Murine Progeria Model Exhibits Delayed Fracture Healing with Dysregulated Local Immune Response.

Background: Bone fracture is one of the most globally prevalent injuries, with an estimated 189 million bone fractures occurring annually. Delayed union or nonunion occurs in up to 15% of fractures and involves the interruption or complete failure of bone continuity following fracture. Preclinical testing is essential to support the translation of novel strategies to promote improved fracture repair treatment, but there is a paucity of small animal models that recapitulate clinical attributes associated with delayed fracture healing. This study explores whether the Zmpste24 -/- (Z24 -/- ) knockout mouse model of Hutchinson-Gilford progeria syndrome presents with delayed fracture healing. Leveraging the previously characterized Z24 -/- phenotype of genomic instability, epigenetic changes, and fragility, we hypothesize that these underlying alterations will lead to significantly delayed fracture healing relative to age-matched wild type (WT) controls. Methods: WT and Z24 -/- mice received intramedullary fixed tibia fractures at ∼12 weeks of age. Mice were sacrificed throughout the time course of repair for the collection of organs that would provide information regarding the local (fracture callus, bone marrow, inguinal lymph nodes) versus peripheral (peripheral blood, contralateral tibia, abdominal organs) tissue microenvironments. Analyses of these specimens include histomorphometry, µCT, mechanical strength testing, protein quantification, gene expression analysis, flow cytometry for cellular senescence, and immunophenotyping. Results: Z24 -/- mice demonstrated a significantly delayed rate of healing compared to WT mice with consistently smaller fracture calli containing higher proportion of cartilage and less bone after injury. Cellular senescence and pro-inflammatory cytokines were elevated in the Z24 -/- mice before and after fracture. These mice further presented with a dysregulated immune system, exhibiting generally decreased lymphopoiesis and increased myelopoiesis locally in the bone marrow, with more naïve and less memory T cell but greater myeloid activation systemically in the peripheral blood. Surprisingly, the ipsilateral lymph nodes had increased T cell activation and other pro-inflammatory NK and myeloid cells, suggesting that elevated myeloid abundance and activation contributes to an injury-specific hyperactivation of T cells. Conclusion: Taken together, these data establish the Z24 -/- progeria mouse as a model of delayed fracture healing that exhibits decreased bone in the fracture callus, with weaker overall bone quality, immune dysregulation, and increased cellular senescence. Based on this mechanism for delayed healing, we propose this Z24 -/- progeria mouse model could be useful in testing novel therapeutics that could address delayed healing. The Translational Potential of this Article: This study employs a novel animal model for delayed fracture healing that researchers can use to screen fracture healing therapeutics to address the globally prevalent issue of aberrant fracture healing.

The revision hip arthroscopy complex: capsular deficiency, labral deficiency, femoral over-resection and adhesions can result in good survivorship with revision hip arthroscopy.

To evaluate the patient-reported outcomes (PROs) and survivorship of combined arthroscopic hip labral reconstruction/augmentation, capsular reconstruction, femoral neck remplissage and lysis of adhesions. Patients ≥18 years old who underwent this combination of procedures during revision hip arthroscopy and were eligible for minimum 2-year follow-up were identified. PRO scores including Hip Outcome Score (HOS)-Activities of Daily Living scale, HOS-Sports scale, modified Harris Hip Score, Short Form 12, and Western Ontario & McMaster Universities Osteoarthritis Index, patient satisfaction and failure rates were analyzed. Seven patients (5 females and 2 males) with average age of 45.0 ± 5.2 (range: 40-54 years) met inclusion criteria. Patients had a median of 1 (range: 1-3) prior hip surgery at an outside institution. All patients had previously undergone femoral osteoplasty, and 85% (6/7) of patients had a labral repair performed. Four patients had no capsule closure performed in their prior procedures. Six patients were available for minimum 2-year follow-up. Two patients converted to total hip arthroplasty: one patient with four prior hip arthroscopies and the other had advanced osteoarthritis with outerbridge grade 3/4 defects requiring microfracture. Mean patient satisfaction was 7 (range: 2-9). At mean follow-up of 3 years, most patients who underwent the combination of labral reconstruction, capsular reconstruction, femoral neck remplissage and lysis of adhesions during revision hip arthroscopy demonstrated improved PROs. This salvage procedure has the potential to restore hip function in patients who have failed an initial hip arthroscopy procedure. In patients with these pathologies present and concomitant joint space narrowing, a total hip arthroplasty may be a more appropriate salvage option.