Stem Cells and Bone Tissue Engineering.

Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard for restoring function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in the incorporation with the host bone as well as its cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells that are delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells, including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells, urine-derived stem cells, stem cells from apical papilla, and induced pluripotent stem cells, for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles that are delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hoped that in the future, these preclinical results will translate into new regenerative therapies for bone defect repair.

Improved Functional Outcomes of Combined Hip Arthroscopy and Periacetabular Osteotomy at Minimum 2-Year Follow-Up.

PURPOSE: To evaluate patient-reported outcomes (PROs) and survivorship at minimum 2-year follow-up after combined hip arthroscopy and periacetabular osteotomy (PAO) performed in the setting of a single anesthetic event. METHODS: Patients who underwent combined hip arthroscopy (M.J.P.) and PAO (J.M.M.) between January 2017 and June 2020 were identified. Preoperative and minimum 2-year postoperative PROs including Hip Outcome Score-Activities of Daily Living (HOS-ADL), HOS-Sport, modified Harris Hip Score (mHHS), Western Ontario and McMaster Universities Osteoarthritis Index, 12-Item Short Form Survey Mental Component Scores (SF-12 MCS), and 12-Item Short Form Survey Physical Component Score were collected and compared in addition to revision rate, conversion to total hip arthroplasty (THA), and patient satisfaction. RESULTS: Twenty-four of 29 patients (83%) eligible for the study were available for 2-year minimum follow-up with a median follow-up time of 2.5 years (range, 2.0-5.0). There were 19 females and 5 males with mean age of 31 ± 12 years. Mean preoperative lateral center edge angle was 20° ± 5° and alpha angle was 71° ± 11°. One patient underwent reoperation for removal of a symptomatic iliac crest screw at 11.7 months after operation. Two patients, a 33-year-old woman and a 37-year-old man, were converted to THA at 2.6 and 1.3 years, respectively, following the combined procedure. Both patients had a Tönnis grade of 1 on radiographs, as well as bipolar Outerbridge grade III/IV defects requiring microfracture of the acetabulum. For patients who did not convert to THA (n = 22), there was significant improvement from before to after surgery for all scores (P < .05) except SF-12 MCS. The minimal clinically significant difference and patient-acceptable symptom state rates for HOS-ADL, HOS-Sport, and mHHS were 72%, 82%, 86%, and 95%, 91%, and 95%, respectively. Median patient satisfaction was 10 (range, 4 to 10). CONCLUSIONS: Single-stage combined hip arthroscopy with periacetabular osteotomy for patients with symptomatic hip dysplasia results in improvement in PROs and arthroplasty free survivorship of 92% at median 2.5 year follow-up. LEVEL OF EVIDENCE: Level IV, case series.

Magnetic Resonance Imaging Approximates Labral Width at the 9-, 12-, and 3-O'Clock Positions in the Setting of Revision Hip Arthroscopy.

PURPOSE: To compare preoperative magnetic resonance imaging (MRI) and intraoperative measurements of labral width and determine whether MRI can reliably predict labral width in the setting of revision surgery. METHODS: Patients who underwent revision hip arthroscopy with labral repair performed by a single surgeon from January 2008 to December 2015 were identified retrospectively from a prospectively collected database. The width of the labrum was measured intraoperatively at the time of surgery. Two orthopaedic surgeons performed labral width measurements on MRI scans at 3 standardized locations using the clock-face method. Interobserver and intraobserver reliabilities were calculated, and comparisons between intraoperatively measured labral widths and MRI measurements were performed. RESULTS: Fifty-eight patients who underwent revision hip arthroscopy were enrolled in the study. The average labral width measurements at the 3-, 12-, and 9-o'clock positions were 7.4 mm (standard deviation [SD], 1.2 mm), 7.5 mm (SD, 1.4 mm), and 6.6 mm (SD, 1.2 mm), respectively, on MRI compared with 6.7 mm (SD, 2.1 mm), 6.5 mm (SD, 2.5 mm), and 7.0 mm (SD, 1.9 mm), respectively, when measured intraoperatively. The average intraoperative measurements were smaller than the MRI measurements at the 3-o'clock (P = .03) and 12-o'clock (P = .01) positions. The inter-rater intraclass correlation coefficients between the 2 surgeons exhibited good agreement (0.612) at the 3-o'clock position, fair agreement (0.498) at the 12-o'clock position, and poor agreement (0.171) at the 9-o'clock position. The positive predictive values of the MRI measurements were 72% at the 3-o'clock position, 68% at the 12-o'clock position, and 88% at the 9-o'clock position for identifying a labral width of 6 mm or greater. CONCLUSIONS: The results of this study show that MRI-measured labral width and actual labral width measured at the time of revision arthroscopy are usually within 1 mm of each other. LEVEL OF EVIDENCE: Level II, diagnostic study investigating diagnostic test.

Correlation of Acromial Morphology With Risk and Direction of Shoulder Instability: An MRI Study.

BACKGROUND: The influence of bony morphology on the development of posterior shoulder instability is not well known. PURPOSE: To determine if acromial morphology, as measured on magnetic resonance imaging (MRI), is associated with posterior or anterior shoulder instability. DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: MRI measurements of posterior acromial coverage (PAC), posterior acromial height (PAH), posterior acromial tilt (PAT), and anterior acromial coverage (AAC) were completed for 3 separate matched groups who underwent surgical intervention: posterior instability, anterior instability, and a comparison group of patients who underwent arthroscopic surgery for snapping scapula. Inclusion criteria were patients with recurrent instability <40 years of age without multidirectional instability, glenoid bone loss >13.5%, or glenoid retroversion >10%. RESULTS: Overall, 37 patients were included in each group. PAC was significantly less in the posterior instability group than in the anterior instability and comparison groups (68.3° vs 88.7° vs 81.7°; P < .001). PAH was significantly greater in the posterior group than in the anterior instability group (11.0 mm vs -0.1 mm; P < .001) and comparison group (0.7 mm; P < .001). There was no difference between the posterior and anterior groups in terms of PAT or AAC (P = .45 and P = .05, respectively). PAT was significantly smaller in the posterior instability group than the comparison group (55.2° vs 62.2°; P = .026). The anterior and comparison groups were not significantly different in PAH or PAT (P = .874 and P = .067, respectively) but were significantly different in AAC (P = .026). CONCLUSION: A higher and flatter posterior acromion, as measured on preoperative MRI, appears to be associated with patients who require arthroscopic capsulolabral repair due to posterior shoulder instability. This information may help clinicians to both diagnose and predict the need for operative intervention for patients with posterior labral tears.

The Relationship Between the Joint Space and Outcomes After Hip Arthroscopic Surgery for Femoroacetabular Impingement: Reevaluating the 2-mm Rule.

BACKGROUND: A limited joint space (<2 mm) is associated with poorer outcomes and conversion to total hip arthroplasty (THA) after hip arthroscopic surgery. As indications for hip arthroscopic surgery expand, it is important to reevaluate established risk factors among large patient populations. PURPOSE: To reevaluate the relationship between the radiographic joint space and outcomes after hip arthroscopic surgery and to assess the validity of a joint space of 2 mm as the accepted cutoff for successful hip arthroscopic surgery. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients aged 18 to 50 years who underwent hip arthroscopic surgery for femoroacetabular impingement between January 2008 and December 2016 and had a minimum 2-year follow-up were included. Patients with previous ipsilateral hip surgery, a history of hip fractures, dysplasia (lateral center-edge angle <20°), or osteoarthritis (Tonnis grade >2) were excluded. The joint space was categorized as diminished (≤2 mm), borderline (>2 to ≤3 mm), or preserved (>3 mm). Minimum 2-year patient-reported outcomes (modified Harris Hip Score [mHHS], Hip Outcome Score-Activities of Daily Living [HOS-ADL], Hip Outcome Score-Sports-Specific Subscale [HOS-SSS]), revision rates, and rates of conversion to THA were compared between groups. RESULTS: A total of 699 patients (782 hips) with a mean age of 33.8 ± 10.1 years met 2-year inclusion criteria. The mean follow-up time was 4.2 ± 2.1 years. Overall, 51 hips (6.5%) had a diminished joint space, 297 (38.0%) had a borderline joint space, and 434 (55.5%) had a preserved joint space. Patients with a diminished joint space had larger femoral and acetabular defects compared with those with larger joint spaces. All groups had improved patient-reported outcome scores compared with baseline (P < .001 for all), and there were no differences between the groups in the percentage of patients who reached the minimal clinically important difference or patient acceptable symptom state. There were also no differences between the groups in revision rates (P = .95). A greater number of hips with a diminished joint space converted to THA (n = 8 [15.7%]) compared with those with a borderline (n = 9 [3.0%]) or preserved (n = 9 [2.1%]) joint space (P < .001). Considering joint space as a continuous variable, adjusted logistic regression showed that for every millimeter decrease in the joint space, the odds of conversion to THA increased by a factor of 2.5 (odds ratio, 2.5 [95% CI, 1.6-3.8]). CONCLUSION: This study demonstrated that patients with a diminished joint space were at a higher risk of conversion to THA. Although 2 mm should not serve as a strict cutoff, patients should be counseled based on their preoperative radiographic findings accordingly.

Timing From Symptom Onset to Hip Arthroscopy Does Not Affect Patient-Reported Outcome Measures for the Treatment of Femoroacetabular Impingement in Adolescent Patients.

PURPOSE: To evaluate symptom duration and its relationship to patient-reported outcomes (PROs) and survivorship after hip arthroscopy in adolescents. METHODS: Patients ≤18 at time of primary hip arthroscopy for femoroacetabular impingement (FAI) between January 2011 and September 2018 were included. Exclusion criteria consisted of history of previous ipsilateral hip surgery, presence of osteoarthritis or dysplasia on preoperative radiographs, previous hip fracture, or history of slipped capital femoral epiphysis or Legg-Calve-Perthes disease. Minimum 2-year PROs (modified Harris Hip Score, Hip Outcome Score [HOS]-Activities of Daily Living, HOS-Sport Scale, Short Forms 12 [SF-12]), minimum clinically significant difference (MCID) and patient-acceptable symptom state (PASS) rates, and revision surgery rates were compared based on symptom duration. RESULTS: Two-year minimal follow-up was obtained for 111 patients (134 hips) (80%), including 74 females and 37 males with a mean age of 16.4 ± 1.1 (range 13.0-18.0). The mean symptom duration was 17.2 ± 15.2 months (range 43 days to 6.0 years). Ten patients (11 hips), 6 females (7 hips) and 4 males, required revision surgery at an average of 2.3 ± 1.0 years (range 0.9-4.3 years). At a mean follow-up of 4.8 ± 2.2 years (range 2-10 years), there were statistically significant improvements in all PROs (P < .05 for all). Symptom duration showed no significant correlation to post-operative scores (correlation coefficient range -0.162 to -0.078, P > .05 for all). Symptom duration ≤12 months versus >12 months or as a continuous variable was not a predictor for requiring revision surgery or achieving MCID/PASS (95% confidence interval crosses 1 for all). CONCLUSIONS: In an adolescent cohort of symptomatic FAI patients who underwent hip arthroscopy, there is no difference in PRO measures when analyzing symptom duration by arbitrary time intervals or as a continuous variable. LEVEL OF EVIDENCE: Level IV, case series.

MRL/MpJ Mice Resist to Age-Related and Long-Term Ovariectomy-Induced Bone Loss: Implications for Bone Regeneration and Repair.

Osteoporosis and age-related bone loss increase bone fracture risk and impair bone healing. The need for identifying new factors to prevent or treat bone loss is critical. Previously, we reported that young MRL/MpJ mice have superior bone microarchitecture and biomechanical properties as compared to wild-type (WT) mice. In this study, MRL/MpJ mice were tested for resistance to age-related and long-term ovariectomy-induced bone loss to uncover potential beneficial factors for bone regeneration and repair. Bone tissues collected from 14-month-old MRL/MpJ and C57BL/6J (WT) mice were analyzed using micro-CT, histology, and immunohistochemistry, and serum protein markers were characterized using ELISAs or multiplex assays. Furthermore, 4-month-old MRL/MpJ and WT mice were subjected to ovariectomy (OV) or sham surgery and bone loss was monitored continuously using micro-CT at 1, 2, 4, and 6 months (M) after surgery with histology and immunohistochemistry performed at 6 M post-surgery. Sera were collected for biomarker detection using ELISA and multiplex assays at 6 M after surgery. Our results indicated that MRL/MpJ mice maintained better bone microarchitecture and higher bone mass than WT mice during aging and long-term ovariectomy. This resistance of bone loss observed in MRL/MpJ mice correlated with the maintenance of higher OSX+ osteoprogenitor cell pools, higher activation of the pSMAD5 signaling pathway, more PCNA+ cells, and a lower number of osteoclasts. Systemically, lower serum RANKL and DKK1 with higher serum IGF1 and OPG in MRL/MpJ mice relative to WT mice may also contribute to the maintenance of higher bone microarchitecture during aging and less severe bone loss after long-term ovariectomy. These findings may be used to develop therapeutic approaches to maintain bone mass and improve bone regeneration and repair due to injury, disease, and aging.

Outcomes for Treatment of Capsulolabral Adhesions With a Capsular Spacer During Revision Hip Arthroscopy.

BACKGROUND: The presence of adhesions is a common source of pain and dysfunction after hip arthroscopic surgery and an indication for revision surgery. The placement of a capsular spacer in the capsulolabral recess after lysis of adhesions has been developed to treat and prevent the recurrence of adhesions. PURPOSE: To evaluate patient-reported outcomes (PROs) and survivorship at a minimum of 2 years after revision hip arthroscopic surgery with capsular spacer placement for capsular adhesions. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between January 2013 and June 2018, a total of 95 patients (99 hips) aged ≥18 years underwent revision hip arthroscopic surgery for the treatment of capsular adhesions with the placement of a capsular spacer. Overall, 53 patients (56 hips) met the inclusion criteria and had a minimum 2-year follow-up, forming the cohort of this study. Exclusion criteria included confounding metabolic bone diseases (eg, Legg-Calve-Perthes disease, Marfan syndrome), labral deficiency, or advanced osteoarthritis (Tönnis grade 2 or 3). Preoperative and postoperative outcome scores (modified Harris Hip Score [mHHS], Hip Outcome Score-Activities of Daily Living [HOS-ADL], Hip Outcome Score-Sport-Specific Subscale [HOS-SSS], 12-Item Short Form Health Survey [SF-12], and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were collected and compared in addition to the revision rate, conversion to total hip arthroplasty, and patient satisfaction. RESULTS: The mean age of the cohort was 32 ± 11 years, with 32 female hips (57%) and a median number of previous hip arthroscopic procedures of 1 (range, 1-5). The arthroplasty- and revision-free survivorship rate at 2 years was 91%. Overall, 5 patients (6 hips; 11%) underwent revision surgery at a mean of 2.4 ± 1.4 years after capsular spacer placement, with symptomatic capsular defects being the most common finding. There were 4 patients (7%) who converted to total hip arthroplasty. For hips not requiring subsequent surgery (n = 46), there was a significant improvement in outcome scores except for the SF-12 Mental Component Summary, with rates of achieving the minimal clinically important difference of 70%, 70%, and 65% for the mHHS, HOS-ADL, and HOS-SSS, respectively. CONCLUSION: Capsular spacers, as part of a systematic approach including lysis of adhesions with early and consistent postoperative physical therapy including circumduction exercises, resulted in improved PROs as well as high arthroplasty- and revision-free survivorship (91%) at a minimum 2-year follow-up. Capsular spacers should be considered in revision hip arthroscopic procedures when an adequate labral volume remains but adhesions continue to be a concern.

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.

Effect of Anchor Density on Functional Outcomes After Arthroscopic Hip Labral Repair.

BACKGROUND: While labral repair has been widely adopted as the first line treatment for labral injury during hip arthroscopy, there is no widespread consensus on the procedural technique, including the number of anchors that should be used to avoid recurrent instability and revision surgery. PURPOSE: To determine if anchor density can predict patient-reported outcomes after arthroscopic labral repair in the hip. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients aged 18 to 50 years who underwent primary hip arthroscopic surgery with labral repair between January 2011 and December 2016 were identified from a prospectively collected database. Exclusion criteria consisted of previous ipsilateral surgery, osteoarthritis (Tönnis grade >1), and severe cartilage defects (Outerbridge grade III/IV) or concomitant labral reconstruction, capsular reconstruction, or microfracture. Minimum 2-year patient-reported outcomes (modified Harris Hip Score [mHHS], Hip Outcome Score [HOS]-Activities of Daily Living [ADL], HOS-Sport Specific Subscale [SSS], 12-Item Short Form Health Survey [SF-12]), rates of achieving the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) for each score, revision surgery rate, and rate of conversion to total hip arthroplasty (THA) were compared based on anchor density (number of anchors per millimeter of labral tear). RESULTS: A total of 634 hips (575 patients) with a mean age of 30.4 ± 9.5 years (range, 18.0-49.9 years) met inclusion criteria. The mean labral tear size was 31 ± 11 mm (range, 2-70 mm) with a median number of anchors used for labral repair of 3 (range, 1-7) and mean anchor density of 0.11 ± 0.08 anchors (range, 0.03-1.33) per millimeter of labral tear. Hips with a minimum 2-year follow-up (451/634 [71.1%]) had significant improvements on the mHHS, HOS-ADL, HOS-SSS, and SF-12 Physical Component Summary (P < .001 for all). There was no significant correlation detected between anchor density or number of anchors used and postoperative scores (correlation coefficient range, -0.05 to 0.17; P > .05 for all). The rate of revision surgery was 6.4% (28 patients), with 8 hips found to have labral tears and/or deficiency on revision. Additionally, 6 hips (1.3%) had to undergo THA at a mean of 3.6 ± 2.1 years (range, 2.0-5.5 years). CONCLUSION: Anchor density did not have a correlation with postoperative outcomes, achieving the MCID or PASS, revision hip arthroscopic surgery, complications, or conversion to THA.

Preoperative Magnetic Resonance Imaging Predicts Intraoperative Labral Width at the 9-O'clock and 12-O'clock Positions in Primary Hip Arthroscopy.

Purpose: To determine whether preoperative magnetic resonance imaging (MRI) can reliably predict labral width in primary hip arthroscopy. Methods: Patients who underwent primary hip arthroscopy with labral repair performed by a single surgeon from January 2008 to December 2015 were identified retrospectively from a prospectively collected database. The width of the labrum was measured intraoperatively at the time of surgery. Two orthopaedic surgeons performed labral width measurements on MRI at 3 standardized locations using the clock-face method at 2 time points, 4 weeks apart. Interobserver and intraobserver reliabilities were calculated, and comparisons were performed between intraoperatively measured labral widths and MRI measurements at the 3 positions. Results: Fifty-eight patients who underwent primary hip arthroscopy were enrolled in the study. The average labral width measurements at the 3-, 12-, and 9-o'clock positions were 6.8 mm (standard deviation [SD], 1.1), 6.9 mm (SD, 1.3 mm), and 6.2 mm (SD, 0.9 mm), respectively, on MRI compared with 7.2 mm (SD, 1.5 mm), 7.8 mm (SD, 2.3 mm), and 7.3 mm (SD, 1.6 mm), respectively, when measured intraoperatively. The intraoperative measurements were larger than the MRI measurements at all 3 locations, with significant differences at the 12-o'clock (P = .008) and 9-o'clock (P < .001) positions. The positive predictive value of the MRI measurements was 92% at the 3-o'clock position, 89% at the 12-o'clock position, and 94% at the 9-o'clock position for identifying a labral width of 6 mm or greater. Conclusions: Measuring labral width on MRI yielded, on average, a value that is smaller than the intraoperatively measured width in primary hip arthroscopy procedures. MRI can predict a labral width of 6 mm or greater in at least 89% of cases, which will assist in operative planning. Clinical Relevance: The clinical implications of this research include identifying the rare patients in whom more advanced hip arthroscopy procedures may be indicated, such as labral augmentation, in instances of inadequate labral volume that will adequately restore the biomechanics of the suction seal.

Bone morphogenetic protein 4 rescues the bone regenerative potential of old muscle-derived stem cells via regulation of cell cycle inhibitors.

BACKGROUND: Bone morphogenetic protein 4 (BMP4) promotes the osteogenic differentiation and the bone regenerative potential of muscle-derived stem cells (MDSCs). BMP4 also promotes the self-renewal of both embryonic and somatic stem cells; however, BMP4 signaling activity significantly decreases with age. Cyclin-dependent kinase inhibitors P16INK4A (P16) and P18INK4C (P18) induce early G1-phase cell cycle blockade by targeting cyclin-dependent kinase 4/6. It is still unclear if BMP4 affects the bone regenerative potential of old MDSCs through regulation of P16 and P18 expression. METHODS: Young and old MDSCs were isolated from 3 week (young) and 2-year-old (old) mice. In vitro cell proliferation and multipotent differentiation were performed for young and old MDSCs both before and after BMP4/GFP transduction. Cell cycle genes were analyzed using Q-PCR. The bone regenerative potential of young and old MDSCs transduced with BMP4/GFP were compared using Micro-CT and histological analysis. The bone regenerative potential of young and old MDSCs was also compared between single and double transduction (higher BMP4 levels expression). The cell proliferation, mitochondrial function and osteogenic differentiation was also compared in vitro between cells that have been transduced with BMP4GFP (single and double transduction). The correlation of bone regeneration capacity of young and old MDSCs with P16 and P18 expression was further evaluated at 10 days after cell transplantation using histology and western blot analysis. RESULTS: Old murine MDSCs (MDSCs) exhibit reduced proliferation and multi-lineage differentiation potential with or without BMP4 stimulation, when compared to young murine MDSCs. Old MDSCs express significantly higher P16 and lower P18, with more cells in the G0/1 phase and fewer cells in the G2/M phase, compared to young MDSCs. Old MDSCs retrovirally transduced to express BMP4 regenerated less bone in a critical size skull defect in CD-1 nude mice when compared to young retrovirally transduced MDSCs expressing similar BMP4 levels and contribute less to the new regenerated new bone. Importantly, both young and old MDSCs can regenerate more bone when BMP4 expression levels are increased by double-transduction with the retroviral-BMP4/GFP. However, the bone regeneration enhancement with elevated BMP4 was more profound in old MDSCs (400% at 2 weeks) compared to young MDSCs (200%). Accordingly, P18 is upregulated while P16 is downregulated after BMP4 transduction. Double transduction did not further increase cell proliferation nor mitochondrial function but did significantly increase Osx expression in both young and old MDSCs. Old MDSCs had even significant higher Osx levels as compared to young MDSCs following double transduction, while a similar Alp expression was observed between young and old MDSCs after double transduction. In addition, at 10 days after cell transplantation, old MDSCs having undergone double transduction regenerated bone more rapidly as showed by Alcian blue and Von Kossa staining. Western blot assays demonstrated that old MDSCs after retro-BMP4/GFP double transduction have significantly lower P18 expression levels when compared to young BMP4-transduced MDSCs. In addition, P18 expression was slightly increased in old MDSCs after double transduction when compared to single transduction. P16 expression was not detectable for both young and two old BMP4/GFP transduced MDSCs groups. CONCLUSIONS: In summary, BMP4 can offset the adverse effect of aging on the osteogenic differentiation and the bone regenerative potential of old MDSCs via up-regulation of P18 and down-regulation P16 expression.

Concomitant Glenolabral Articular Disruption (GLAD) Lesion is Not Associated With Inferior Clinical Outcomes After Arthroscopic Bankart Repair for Shoulder Instability: A Retrospective Comparative Study.

Purpose: The purpose of this study was to compare outcomes between anterior shoulder instability patients with and without glenolabral articular disruption (GLAD) lesions after undergoing arthroscopic Bankart repair and to evaluate potential risk factors for inferior outcomes and recurrent instability. Methods: Prospectively collected data were retrospectively reviewed for patients who underwent arthroscopic Bankart repair with and without GLAD lesions at a minimum of 2 years follow-up. Consecutive patients were matched by age, sex, and number of anchors. Patient-reported outcomes (PROs) were evaluated before and after surgery, including American Shoulder and Elbow Surgeons, Single Assessment Numeric Evaluation, Quick Disabilities of the Arm, Shoulder and Hand, Short Form-12 score, and satisfaction. Recurrent dislocation, subjective instability, and reoperation were analyzed. Additionally, PROs were assessed on the basis of GLAD lesion characteristics. Results: A total of 54 patients (27 GLAD, 27 control) with a mean age of 28.9 ± 11.6 years were analyzed at mean 4.5 ± 1.9 years (range, 2-9 years) follow-up. Thirty-eight (70.3%) of the participants were male. Patients in both groups experienced significant improvements in all PROs (P ≤ .006 for all measures) and reported high median satisfaction (scale 1-10: 10 vs 10, P = .290) at final follow-up. Two patients in the GLAD cohort and 1 in the control cohort underwent reoperation (P = .588). Four (14.8%) patients in each group reported recurrent dislocation (P = 1.0). Additionally, 2 (7.4%) GLAD patients and 1 (3.7%) control patient reported subjective shoulder instability after surgery (P = 1.0). No significant differences in PROs were observed based on anchor/labral advancement or treatment with microfracture, nor were significant correlations observed between GLAD lesion size and PROs (P > .05 for all). Conclusion: Arthroscopic Bankart repair in patients with GLAD lesions resulted in significantly improved outcomes with high satisfaction, which was no different when compared with those without GLAD lesions. Level of Evidence: Level III, retrospective comparative study.

Surgical Treatment of Acetabular Dysplasia With Labral Tears.

Acetabular dysplasia results in abnormal forces across the hip joint and can result in both labral tears and cartilage degeneration. A continuum exists from classic dysplasia to normal acetabular morphology. Diagnosis is aided by several radiographic measurements and parameters including a lateral center edge angle of less than 20°, an anterior center edge angle of less than 20°, a Sharp's angle of greater than 42°, and a Tonnis angle of greater than 10°, or version abnormalities. When patients with acetabular dysplasia present with intra-articular hip pain, skeletal maturity, and preserved radiographic joint space, a periacetabular osteotomy (PAO) is considered as a surgical treatment option when conservative measures have failed. The Bernese PAO was developed in 1984 as a way for reorienting the acetabulum to restore more normal femoral head coverage and orientation. The long-term results of this procedure have been promising with 10-year and 20-year survivorships of approximately 85% and 60%, respectively. When dysplasia is coupled with a labral tear or other intra-articular pathology including focal chondral damage, ligamentum teres tears, or capsular defects, hip arthroscopy and PAO are performed. Although there is a paucity in the literature of the long-term evidence for the combined procedure, early results indicate improved patient reported outcome measures. Appropriate treatment of borderline hip dysplasia remains controversial.

Management of Complex and Revision Anterior Shoulder Instability.

Treatment of recurrent anterior shoulder instability has gained significant interest in recent years and involves evaluation of both glenoid and humeral sided bone loss. Decision making is more complex in patients with significant humeral or glenoid bone defects or in those who underwent previous instability surgery. Appropriate assessment of the glenoid track is necessary as "off track" lesions typically require treatments beyond arthroscopic labral repair alone. In those with significant humeral or glenoid sided bone loss, the authors recommend three-dimensional computed tomography in addition to magnetic resonance imaging for accurate evaluation. The Glenoid Track Instability Management Score is a useful guide to help direct treatment by using the glenoid track as well as other known risk factors for recurrence. In circumstances with significant glenoid bone loss, typically over 20%, a coracoid transfer such as the Latarjet is recommended. In patients that previously failed a coracoid transfer, the authors recommend a distal tibia allograft; however, distal clavicle and iliac crest autograft have also been reported to have high success rates. In those with large Hill-Sachs lesions, remplissage or bone grafting are recommended. An estimation of the postoperative glenoid track after glenoid bone augmentation is required for appropriate Hill-Sachs lesion treatment. The authors typically recommend against revision instability surgical treatment with arthroscopic repair alone.

Meniscus Repair Part 2: Technical Aspects, Biologic Augmentation, Rehabilitation, and Outcomes.

Multiple meniscal repair techniques exist, and successful healing and excellent patient outcomes have been reported with a variety of all-inside and open techniques. Increased awareness and recognition of root tears and meniscocapsular separations are topics of recent interest. The ideal treatment of these injuries remains uncertain, and definitive recommendations regarding their treatment are lacking. Postoperative protocols regarding weight bearing and range of motion are controversial and require future study. The role of biologics in the augmentation of meniscal repair remains unclear but promising. An evidence-based individualized approach for meniscal repair focusing on clinical outcomes and value is essential.

Comprehensive Arthroscopic Management of Shoulder Arthritis.

Glenohumeral arthritis is a challenging problem, especially in the young, active patient. After nonoperative treatment, including activity modification, anti-inflammatory medications, physical therapy, and injections, is exhausted, surgical treatment ranging from simple debridement to arthroplasty is commonly offered. Given concerns regarding arthroplasty implant longevity, there is an interest in joint-preserving procedures. In this difficult population, the authors recommend a systematic, inclusive approach to the array of pathologies encountered in the setting of early glenohumeral arthritis: the Comprehensive Arthroscopic Management (CAM) procedure. CAM consists of the combination of arthroscopy, glenohumeral chondroplasty, synovectomy, loose body removal, microfracture, capsular release, humeral osteoplasty, axillary nerve neurolysis, subacromial decompression, and biceps tenodesis. Key perioperative care includes the use of regional nerve blocks to allow immediate physical therapy with the goal of restoring range of motion by 4 to 6 weeks with strengthening beginning at 6 to 12 weeks and return to full activities at 4 to 6 months. Although this is still considered a bridging procedure, the literature has reported 92% survival at 1 year, 85% survival at 2 years, 77% survival at 5 years, and 63% survival at 10 years. Predictors of failure of the CAM procedure include joint space <2 mm, flattening of the humeral head, and abnormal posterior glenoid morphology. Patient selection and education is therefore essential for optimizing outcomes.

Meniscus Repair Part 1: Biology, Function, Tear Morphology, and Special Considerations.

Knowledge of anatomy and physiology of the meniscus is essential for appropriate treatment. The unique anatomy of the medial and lateral meniscus and blood supply play an important role in decision making. Controversy exists regarding the optimal treatment of meniscal tears including débridement, repair, root repair, and transplantation. The unique tear location and morphology thus plays an essential role in determination of appropriate treatment. Repair is generally advised in tear types with healing potential to preserve meniscal function and joint health.

Outcomes of Arthroscopic Anterior Labroligamentous Periosteal Sleeve Avulsion Lesions: A Minimum 2-Year Follow-up.

BACKGROUND: Anterior labroligamentous periosteal sleeve avulsion (ALPSA) lesions can occur in recurrent anterior shoulder instability, which may lead to the labrum scarring medially to the glenoid. ALPSA lesions have also been associated with greater preoperative dislocations, larger Hill-Sachs lesions, and greater degrees of glenoid bone loss. Therefore, patients with these lesions have historically had a higher failure rate after repair, with nearly double the recurrent instability rate compared with those undergoing standard arthroscopic Bankart repair. PURPOSE: To compare minimum 2-year outcomes of arthroscopic mobilization and anatomic repair of ALPSA lesions with those after standard arthroscopic Bankart repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Consecutive patients who underwent arthroscopic repair of ALPSA lesions were matched in a 1-to-3 fashion to patients who underwent standard Bankart repair by age, sex, number of previous ipsilateral shoulder instability surgical procedures, and number of anchors used. Patient-reported outcome (PRO) scores were compared preoperatively and postoperatively (American Shoulder and Elbow Surgeons [ASES]; 12-Item Short Form Health Survey [SF-12] Physical Component Summary [PCS]; Single Assessment Numeric Evaluation [SANE]; shortened version of Disabilities of the Arm, Shoulder and Hand; and satisfaction). Recurrent instability, on- versus off-track Hill-Sachs lesion, and reoperation rates were analyzed. RESULTS: A total of 100 shoulders (25 ALPSA and 75 Bankart) with an overall mean age of 25.7 years were evaluated. Patients in the ALPSA group demonstrated significant improvements in the ASES (preoperative, 74.8; postoperative, 89.7; P = .041) and SF-12 PCS (preoperative, 46.9; postoperative, 53.4; P = .021) scores but not the SANE score (preoperative, 65.2; postoperative, 75.3; P = .311). Patients in the Bankart group had significant improvements in all outcome scores at final follow-up: ASES (preoperative, 67.1; postoperative, 90.3), SANE (preoperative, 58.0; postoperative, 85.7), and SF-12 PCS (preoperative, 45.3; postoperative, 52.9) (all P < .001). There were no significant differences in PRO scores between the groups preoperatively or postoperatively (P > .05). The median satisfaction for the ALPSA group was 10 of 10 and for the Bankart group it was 9 of 10 (P = .094). There was a significantly higher rate of recurrent dislocation in the ALPSA group (8/25 [32.0%]) compared with the Bankart group (10/75 [13.3%]) (P = .040). Additionally, 5 patients (20.0%) in the ALPSA group underwent revision surgery at a mean of 5.6 years, and 8 patients (10.7%) in the Bankart group underwent revision surgery at a mean of 4.4 years (P = .311). CONCLUSION: Despite improvements in the recognition of and surgical techniques for ALPSA lesions, they still lead to significantly higher postoperative dislocation rates; however, no differences in PRO scores were found. These findings highlight the importance of early surgical interventions in anterior shoulder instability with the hope of lessening recurrent instability and the risk of developing an ALPSA lesion, as well as careful assessment of the quality of soft tissues and other risk factors for recurrence when considering what type of shoulder stabilization procedure to perform.

Minimum 2-Year Clinical Outcomes of Medial Meniscus Root Tears in Relation to Coronal Alignment.

BACKGROUND: The effect of coronal plane alignment on the outcomes of repairs of the medial meniscus root remains unclear. HYPOTHESIS: Increased preoperative varus alignment is associated with higher failure rates and lower patient-reported outcomes (PROs) after isolated repair of the medial meniscus root. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients aged 18 years or older who underwent arthroscopy-assisted repair of the medial posterior meniscus root over a 7-year period were included. The mechanical axis of the knee was measured preoperatively. Osteoarthritis was assessed radiographically preoperatively and at the final follow-up according to the Kellgren-Lawrence grading scale. Failure was defined as any patient having to undergo revision root repair, partial meniscectomy of the previously repaired meniscus, debridement, lysis of adhesions, or conversion to arthroplasty. RESULTS: A total of 53 patients (29 women, 24 men) with a mean age of 51.3 years were included in the follow-up analysis. The mean time of follow-up after surgery was 3.3 years (range, 22-77 months). Significant improvements were observed in all PROs analyzed. Decreased varus as measured by alignment percentage was correlated with baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain (P = .023) and WOMAC Stiffness (P = .022). Alignment percentage was also significantly negatively correlated with postoperative WOMAC Stiffness (P = .005) and positively correlated with Lysholm (P = .003) and International Knee Documentation Committee (P = .009) scores. Higher baseline Kellgren-Lawrence grade was correlated with worse postoperative PROs (P < .05), except 12-Item Short Form Health Survey Mental Component Summary and satisfaction. Eight patients who underwent a concomitant high tibial osteotomy (HTO) achieved lower PROs in all scales analyzed, regardless of their alignment. When excluding patients who underwent HTO, postoperative Lysholm score (P = .004) and postoperative WOMAC Stiffness (p = 0.014) were inferior among the patients with >5° of varus. CONCLUSION: Lower extremity alignment closest to neutral correlated with improved PROs. Patients who underwent a concurrent HTO had worse PROs than those who did not undergo HTO.