Maintenance of acetabular correction following PAO: a multicenter study comparing stainless-steel and titanium screws.

Stainless-steel screws are commonly used for fragment fixation during periacetabular osteotomy (PAO) at our institutions. Titanium is reserved for patients with documented nickel allergies. Titanium screws possess a significantly lower Young's modulus than stainless steel and, therefore, potentially less resistance to physiologic loading. Thus, we hypothesized that the use of titanium screws might be associated with changes in acetabular correction prior to healing. The aim of this study was to compare the maintenance of acetabular correction following PAO using stainless-steel or titanium screws. A documented nickel allergy was confirmed with an allergy specialist. Patients' age at surgery, gender and BMI were collected. The lateral center-edge angle of Wiberg (LCEA), medial center-edge angle (MCEA), anterior wall index (AWI), posterior wall index (PWI) and Tönnis angle were measured. The delta value for radiographic parameters was calculated as the difference between values immediately post-operation and at 6 months post-operation. Only age at surgery (P < 0.001) and the pre-operative LCEA (P = 0.013) were significantly different between groups (Tables I and II). The remaining pre- and post-operative radiological measurements were similar (Table II). Comparison of delta values at 6 months follow-up indicated no significant differences between screw types (Table III). No patients in the titanium group had a trans-iliac retrograde screw included in their construct (P = 0.003). All patients healed from their osteotomies. The use of titanium screws in patients with an allergy to nickel was not associated with differences in acetabular correction or the rate of osseous union rates despite its lower inherent mechanical properties.

Development of acetabular retroversion in LCPD hips-an observational radiographic study from early stage to healing.

BACKGROUND: Acetabular retroversion is observed frequently in healed Legg-Calvé-Perthes disease (LCPD). Currently, it is unknown at which stage and with what prevalence retroversion occurs because in non-ossified hips, retroversion cannot be measured with standard radiographic parameters. METHODS: In a retrospective, observational study; we examined pelvic radiographs in children with LCPD the time point of occurrence of acetabular retroversion and calculated predictive factors for retroversion. Between 2004 and 2017, we included 55 children with a mean age of 5.7 ± 2.4 years at diagnosis. The mean radiographic follow-up was 7.0 ± 4.4 years. We used two new radiographic parameters which allow assessment of acetabular version in non-ossified hips: the pelvic width index and the ilioischial angle. They are based on the fact that the pelvic morphology differs depending on the acetabular version. These parameters were compared among the four Waldenström stages and to the contralateral side. Logistic regression analysis was performed to determine predictive factors for acetabular retroversion. RESULTS: Both parameters differed significantly among the stages of Waldenström (p < 0.003 und 0.038, respectively). A more retroverted acetabulum was found in stage II and III (prevalence ranging from 54 to 56%) compared to stage I and IV (prevalence ranging from 23 to 39%). In hips of the contralateral side without LCPD, the prevalence of acetabular retroversion was 0% in all stages for both parameters. Predictive factors for retroversion were younger age at stage II and IV, collapse of the lateral pillar in stage II or a non-dysplastic hip. CONCLUSIONS: This is the first study evaluating acetabular version in children with LCPD from early stage to healing. In the developing hip, LCPD may result in acetabular retroversion and is most prevalent in the fragmentation (stage II) and early healing stage (stage III). Partial correction of acetabular retroversion can occur after healing. This has a potential clinical impact on the timing and type of surgical correction, especially in pelvic osteotomies for correction of acetabular version. LEVEL OF EVIDENCE: Level III, retrospective observational study.

Tissue Engineering Strategies for Treating Avascular Necrosis of the Femoral Head.

Avascular necrosis (AVN) of the femoral head commonly leads to symptomatic osteoarthritis of the hip. In older patients, hip replacement is a viable option that restores the hip biomechanics and improves pain but in pediatric, adolescent, and young adult patients hip replacements impose significant activity limitations and the need for multiple revision surgeries with increasing risk of complication. Early detection of AVN requires a high level of suspicion as diagnostic techniques such as X-rays are not sensitive in the early stages of the disease. There are multiple etiologies that can lead to this disease. In the pediatric and adolescent population, trauma is a commonly recognized cause of AVN. The understanding of the pathophysiology of the disease is limited, adding to the challenge of devising a clinically effective treatment strategy. Surgical techniques to prevent progression of the disease and avoid total hip replacement include core decompression, vascular grafts, and use of bone-marrow derived stem cells with or without adjuncts, such as bisphosphonates and bone morphogenetic protein (BMP), all of which are partially effective only in the very early stages of the disease. Further, these strategies often only improve pain and range of motion in the short-term in some patients and do not predictably prevent progression of the disease. Tissue engineering strategies with the combined use of biomaterials, stem cells and growth factors offer a potential strategy to avoid metallic implants and surgery. Structural, bioactive biomaterial platforms could help in stabilizing the femoral head while inducing osteogenic differentiation to regenerate bone and provide angiogenic cues to concomitantly recover vasculature in the femoral head. Moreover, injectable systems that can be delivered using a minimal invasive procedure and provide mechanical support the collapsing femoral head could potentially alleviate the need for surgical interventions in the future. The present review describes the limitations of existing surgical methods and the recent advances in tissue engineering that are leading in the direction of a clinically effective, translational solution for AVN in future.

Fibrinogen activates focal adhesion kinase (FAK) promoting colorectal adenocarcinoma growth.

BACKGROUND: We previously showed that fibrinogen is a major determinant of the growth of a murine model of colorectal cancer (CRC). OBJECTIVE: Our aim was to define the mechanisms coupling fibrin(ogen) to CRC growth. RESULTS: CRC tumors transplanted into the dorsal subcutis of Fib- mice were less proliferative and demonstrated increased senescence relative to those grown in Fib+ mice. RNA-seq analyses of Fib+ and Fib- tumors revealed 213 differentially regulated genes. One gene highly upregulated in tumors from Fib- mice was stratifin, encoding 14-3-3σ, a master regulator of proliferation/senescence. In a separate cohort, we observed significantly increased protein levels of 14-3-3σ and its upstream and downstream targets (i.e., p53 and p21) in tumors from Fib- mice. In vitro analyses demonstrated increased tumor cell proliferation in a fibrin printed three-dimensional environment compared with controls, suggesting that fibrin(ogen) in the tumor microenvironment promotes tumor growth in this context via a tumor cell intrinsic mechanism. In vivo analyses showed diminished activation of focal adhesion kinase (FAK), a key negative regulator of p53, in Fib- tumors. Furthermore, nuclear magnetic resonance-based metabolomics demonstrated significantly reduced metabolic activity in tumors from Fib- relative to Fib+ mice. Together, these findings suggest that fibrin(ogen)-mediated engagement of colon cancer cells activates FAK, which inhibits p53 and its downstream targets including 14-3-3σ and p21, thereby promoting cellular proliferation and preventing senescence. CONCLUSIONS: These studies suggest that fibrin(ogen) is an important component of the colon cancer microenvironment and may be exploited as a potential therapeutic target.

The corona mortis: is it a rare and dangerous anomaly in adolescents undergoing periacteabular osteotomy?

The corona mortis (CM) is a vascular connection between the obturator and external iliac or internal epigastric vessels that has historically been identified as a source of hemorrhage in pelvic surgery. However, its frequency, location, proximity to the osteotomies performed, vascular contributions and impact on blood loss in patients undergoing periacetabular osteotomy (PAO) are unknown. We sought to identify the frequency, origin, location relative to osteotomies performed during surgery and impact on blood loss of the CM. Preoperative magnetic resonance imaging (MRI) of the hips of 28 adolescent patients (56 hips) undergoing PAO was retrospectively reviewed for the presence of a CM. When identifiable, the size, nature (arterial or venous), orientation, position relative to the iliopectineal eminence (IPE) and associated estimated blood loss (EBL) were recorded. 75% (21/28) of patients possessed an identifiable, ipsilateral CM to the site of PAO, 90% of which were venous and 10% arterial. The vessel was typically 8.3 ± 3.8 mm medial and 11.1 ± 5.3 mm caudal from the anterosuperomedial edge of the IPE. There was no significant difference in the amount of EBL (519 ± 260 versus 694 ± 369 ml) or need for post-op transfusions (1/21 versus 0/7) between patients who possessed a CM and those who did not, respectively (P = 0.21). CM was more prevalent in this study than previously reported. However, the presence of an ipsilateral CM was not associated with an increase in EBL or transfusion during routine PAO surgery using modern surgical techniques.

Bone xenotransplantation: A review of the history, orthopedic clinical literature, and a single-center case series.

BACKGROUND: One-half of all orthopedic surgeries require bone grafting for successful outcomes in fusions, reconstructive procedures, and the treatment of osseous defects resulting from trauma, tumor, infection, or congenital deformity. Autologous bone grafts are taken from the patient's own body and remain the "gold standard" graft choice but are limited in supply and impart significant patient morbidity. Xenograft bone is an attractive alternative from donors with controlled biology, in large supply and at a theoretically lower cost. Clinical results with xenograft bone for orthopedic applications have been mixed in the limited clinical trials published. METHODS: In the current review, we introduce fundamental principles of bone grafting, systematically review all orthopedic clinical studies reporting outcomes on patients transplanted with xenograft bone, and we present our own clinical results from patients grafted with bovine bone in foot and ankle reconstructive procedures. RESULTS: Thirty-one clinical studies were identified for review and the majority (47%) were from spine surgery literature. Favorable results were reported in 44% of studies while 47% of studies reported poor outcomes and discouraged use of xenograft bone products. In our own clinical series, xenograft failed to integrate with host bone in 58% of cases and persistent pain was reported in 83% of cases. CONCLUSIONS: This is the first systematic review of clinical results reported after bone xenotransplantation for orthopaedic surgery applications. Current literature does not support the use of xenograft bone products and our institution's results are consistent with this conclusion. Our laboratory has reported promising pre-clinical results with a xenograft product derived from porcine cancellous bone, but additional testing is required before considering clinical translation.

Pragmatic comparative effectiveness study of multimodal fascia iliaca nerve block and continuous lumbar epidural-based protocols for periacetabular osteotomy.

Perioperative pain management protocols have a significant impact on early surgical outcomes and recovery. We hypothesized that multimodal protocol including fascia iliaca compartment nerve block (MM-FICNB) would decrease the length of hospital stay (LOS) by facilitating earlier mobilization, without compromising analgesia, compared to a traditional lumbar epidural-based protocol (EP). Demographics/comorbidities, surgical/block characteristics and perioperative pain/mobilization data were collected from a prospectively recruited MM-FICNB group (N = 16) and a retrospective EP cohort (N = 16) who underwent PAO using similar surgical techniques, physical therapy/discharge criteria. Association of MM-FICNB group with LOS (primary outcome), postoperative pain, postoperative opioid requirements in morphine equivalent rates (MER) (mcg/kg/h) and time to complete physical therapy were tested using multivariable and survival regression. Patient and surgical characteristics were similar between groups. Median time for FICNB performance was significantly less than epidural (6 versus 15 min; P < 0.001). LOS was significantly decreased in the MM-FICNB group (2.88 ± 0.72 days) compared to the EP group (4.38 ± 1.02 days); P < 0.001. MM-FICNB group had significantly lower MER on POD1 (P = 0.006) and POD2 (P < 0.001), with similar pain scores on all POD. MM-FICNB group was associated with decreased LOS and earlier mobilization (P < 0.001) by covariate-adjusted multivariate regression. Cox proportional hazard regression model showed MM-FICNB subjects had 63 (95% CI 7-571, P < 0.001) times the chance of completing physical therapy goals, compared to EP. Compared to EP, MM-FICNB protocol allowed earlier mobilization and decreased post-surgical hospitalization by 1.5 days, without compromising analgesia, with important implications for value-based healthcare and cost-effectiveness.

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute.

Bone grafting is the second most common tissue transplantation procedure worldwide. One of the alternative methods for bone repair under investigation is a tissue-engineered bone substitute. An ideal property of tissue-engineered bone substitutes is osteoinductivity, defined as the ability to stimulate primitive cells to differentiate into a bone-forming lineage. In the current study, we use a decellularization and oxidation protocol to produce a porcine bone scaffold and examine whether it possesses osteoinductive potential and can be used to create a tissue-engineered bone microenvironment. The decellularization protocol was patented by our lab and consists of chemical decellularization and oxidation steps using combinations of deionized water, trypsin, antimicrobials, peracetic acid, and triton-X100. To test if the bone scaffold was a viable host, preosteoblasts were seeded and analyzed for markers of osteogenic differentiation. The osteoinductive potential was observed in vitro with similar osteogenic markers being expressed in preosteoblasts seeded on the scaffolds and demineralized bone matrix. To assess these properties in vivo, scaffolds with and without preosteoblasts preseeded were subcutaneously implanted in mice for 4 weeks. MicroCT scanning revealed 1.6-fold increased bone volume to total volume ratio and 1.4-fold increase in trabecular thickness in scaffolds after implantation. The histological analysis demonstrates new bone formation and blood vessel formation with pentachrome staining demonstrating osteogenesis and angiogenesis, respectively, within the scaffold. Furthermore, CD31+ staining confirmed the endothelial lining of the blood vessels. These results demonstrate that porcine bone maintains its osteoinductive properties after the application of a patented decellularization and oxidation protocol developed in our laboratory. Future work must be performed to definitively prove osteogenesis of human mesenchymal stem cells, biocompatibility in large animal models, and osteoinduction/osseointegration in a relevant clinical model in vivo. The ability to create a functional bone microenvironment using decellularized xenografts will impact regenerative medicine, orthopedic reconstruction, and could be used in the research of multiple diseases.

Pulseless Supracondylar Humerus Fracture With Anterior Interosseous Nerve or Median Nerve Injury-An Absolute Indication for Open Reduction?

BACKGROUND: Optimal management for a pulseless supracondylar humerus fracture associated with anterior interosseous nerve (AIN) or median nerve injury is unclear. The purpose of this study was to determine the incidence of pulseless supracondylar humerus fractures associated with AIN or median nerve injury, to assess open versus closed surgical management, to determine factors associated with the need for neurovascular intervention, and to report the outcome. METHODS: A retrospective review was performed at 4 pediatric trauma hospitals on all patients who sustained a Gartland III or IV supracondylar humerus fracture with the combination of absent distal palpable pulses and AIN or median nerve injury between 2000 and 2014. Choice of treatment, details regarding preoperative and postoperative exam findings, follow-up course, and outcome were recorded. RESULTS: A total of 71 patients met inclusion criteria; 52 patients (73%) underwent closed reduction (CR); 19 patients (27%) underwent open reduction (OR) and early antecubital fossa exploration. The index procedure of CR plus percutaneous pinning was sufficient treatment in 50 (of 52, 96%) patients with only 2 requiring reoperation. One patient developed compartment syndrome approximately 9 hours after CRPP (13.5 h after time of injury) and underwent emergent fasciotomies. Of the 19 patients who underwent OR and early exploration, 6 needed vascular procedures, 5 required detethering of entrapped surrounding fibrous tissues. Forty patients were diagnosed with median nerve palsy versus 31 diagnosed with AIN palsy. There was no significant difference between patients presenting with median nerve versus AIN palsy, with similar rates of need for OR (10/40; 25% vs. 9/31; 29%), rate of compartment syndrome (3/40; 7.5% vs. 3/31; 9.7%), need for reoperation (4/40; 10% vs. 6.5%), and ultimate resolution of nerve palsy (4/36; 20.1% vs. 3/30; 10%). Compartment syndrome developed in 6 (of 71, 8.5%) patients and was associated with poor perfusion status on presentation and delayed time from injury to surgery. In patients with at least 3-month neurological follow-up, 59 (of 61, 97%) patients had complete resolution of nerve palsy. CONCLUSIONS: Although previous authors have suggested a pulseless SCH fx with an associated AIN or median nerve injury should be treated with exploration and OR, 70% (50/71) of the patients in this series were treated with a CR. In this series, both AIN and median nerve palsies among patients presenting with pulseless extremity and Gartland III or IV SCH fracture, offer similar rates of OR, risk of compartment syndrome, and resolution of nerve palsy. LEVEL OF EVIDENCE: Level IV.

A Decellularized Porcine Xenograft-Derived Bone Scaffold for Clinical Use as a Bone Graft Substitute: A Critical Evaluation of Processing and Structure.

BACKGROUND: Bone grafts are used in approximately one half of all musculoskeletal surgeries. Autograft bone is the historic gold standard but is limited in supply and its harvest imparts significant morbidity to the patient. Alternative sources of bone graft include allografts, synthetics and, less commonly, xenografts which are taken from animal species. Xenografts are available in unlimited supply from healthy animal donors with controlled biology, avoiding the risk of human disease transmission, and may satisfy current demand for bone graft products. METHODS: In the current study, cancellous bone was harvested from porcine femurs and subjected to a novel decellularization protocol to derive a bone scaffold. RESULTS: The scaffold was devoid of donor cellular material on histology and DNA sampling (p < 0.01). Microarchitectural properties important for osteoconductive potential were preserved after decellularization as shown by high resolution imaging modalities. Proteomics data demonstrated similar profiles when comparing the porcine bone scaffold against commercially available human demineralized bone matrix approved for clinical use. CONCLUSION: We are unaware of any porcine-derived bone graft products currently used in orthopaedic surgery practice. Results from the current study suggest that porcine-derived bone scaffolds warrant further consideration to serve as a potential bone graft substitute.

Microspheres containing decellularized cartilage induce chondrogenesis in vitro and remain functional after incorporation within a poly(caprolactone) filament useful for fabricating a 3D scaffold.

In this study, articular cartilage was decellularized preserving a majority of the inherent proteins, cytokines, growth factors and sGAGs. The decellularized cartilage matrix (dCM) was then encapsulated in poly(lactic acid) microspheres (MS + dCM) via double emulsion. Blank microspheres without dCM, MS(-), were also produced. The microspheres were spherical in shape and protein encapsulation efficiency within MS + dCM was 63.4%. The sustained release of proteins from MS + dCM was observed over 4 weeks in vitro. Both MS + dCM and MS(-) were cytocompatible. The sustained delivery of retained growth factors and cytokines from MS + dCM promoted cell migration in contrast to MS(-). Subsequently, chondrogenesis of human mesenchymal stem cells was upregulated in presence of MS + dCM as evidenced from immunohistochemistry, biochemical quantification and qPCR studies. Specifically, collagen II, aggrecan and SOX 9 gene expression were increased in the presence of MS + dCM by an order or more in magnitude compared to MS(-) with concomitant downregulation of hypertrophic genes (COL X) despite being cultured in the absence of chondrogenic media, (p < 0.05). Lastly, microspheres containing alkaline phosphatase (MS + ALP), a surrogate to assess the thermal stability of dCM proteins, incorporated within poly(caprolactone) filaments showed that the enzyme remained functional after filament production by melt extrusion. The establishment of a novel, thermally stable process for producing filaments containing chondroinductive microspheres provides evidence supporting subsequent development of a clinically-relevant, 3D scaffold fabricated from them for osteochondral regeneration and repair.

The Development of a Xenograft-Derived Scaffold for Tendon and Ligament Reconstruction Using a Decellularization and Oxidation Protocol.

PURPOSE: To evaluate the biological, immunological, and biomechanical properties of a scaffold derived by architectural modification of a fresh-frozen porcine patella tendon using a decellularization protocol that combines physical, chemical, and enzymatic modalities. METHODS: Porcine patellar tendons were processed using a decellularization and oxidation protocol that combines physical, chemical, and enzymatic modalities. Scaffolds (n = 88) were compared with native tendons (n = 70) using histologic, structural (scanning electron microscopy, porosimetry, and tensile testing), biochemical (mass spectrometry, peracetic acid reduction, DNA quantification, alpha-galactosidase [α-gal] content), as well as in vitro immunologic (cytocompatibility, cytokine induction) and in vivo immunologic nonhuman primate analyses. RESULTS: A decrease in cellularity based on histology and a significant decrease in DNA content were observed in the scaffolds compared with the native tendon (P < .001). Porosity and pore size were increased significantly (P < .001). Scaffolds were cytocompatible in vitro. There was no difference between native tendons and scaffolds when comparing ultimate tensile load, stiffness, and elastic modulus. The α-gal xenoantigen level was significantly lower in the decellularized scaffold group compared with fresh-frozen, nondecellularized tissue (P < .001). The in vivo immunological response to implanted scaffolds measured by tumor necrosis factor-α and interleukin-6 levels was significantly (P < .001) reduced compared with untreated controls in vitro. These results were confirmed by an attenuated response to scaffolds in vivo after implantation in a nonhuman primate model. CONCLUSIONS: Porcine tendon was processed via a method of decellularization and oxidation to produce a scaffold that possessed significantly less inflammatory potential than a native tendon, was biocompatible in vitro, of increased porosity, and with significantly reduced amounts of α-gal epitope while retaining tensile properties. CLINICAL RELEVANCE: Porcine-derived scaffolds may provide a readily available source of material for musculoskeletal reconstruction and repair while eliminating concerns regarding disease transmission and the morbidity of autologous harvest.

Intraoperative Evaluation of Acetabular Morphology in Hip Arthroscopy Comparing Standard Radiography Versus Fluoroscopy: A Cadaver Study.

PURPOSE: To compare quantitative measurements of acetabular morphology obtained using intraoperative fluoroscopy, to standardized anteroposterior (AP) pelvis radiographs. METHODS: Ten dried human pelvis specimens (20 hips) were imaged using hip-centered fluoroscopy and standardized AP pelvis radiographs. Each hip was evaluated for acetabular version and coverage, including lateral center edge (LCE) angle, acetabular index (AI), total anterior and posterior coverage, and crossover sign. RESULTS: No statistically significant differences existed between the mean LCE angle (fluoroscopy 36.5° ± 8.3° v plain films 36.1° ± 7.9°, P = .59), acetabular index (0.6° ± 8.6° v 0.2° ± 7.1°, P = .61), ACM angle (44.0° ± 2.6° v 44.1° ± 3.8°, P = .89), Sharp's angle (31.8° ± 5.7° v 32.4° ± 3.9°, P = .44), and the total femoral coverage (80.9% ± 6.4% v 80.7% ± 7.5%, P = .83). Conversely, total anterior coverage (30.7% ± 8.5% v 33.3% ± 8.2%, P < .0001) appeared significantly decreased and the total posterior coverage (54.1% ± 6.9% v 49.1% ± 7.8%, P < .0001) appeared significantly increased in fluoroscopy compared with plain film radiographs. Fluoroscopy also failed to identify the presence of a crossover sign in 30% and underestimated the retroversion index (9% ± 16%, v 13% ± 16%, P = .016). CONCLUSIONS: The values for the LCE angle and AI determined by hip-centered fluoroscopy did not differ from those obtained by standardized AP plain film radiography. However, fluoroscopy leads to a more anteverted projection of the acetabulum with significantly decreased total anterior coverage, significantly increased total posterior coverage, and underestimated signs of retroversion compared with standardized AP pelvis radiography. CLINICAL RELEVANCE: This study shows reliable LCE and AI angles but significant differences in the projected anteversion of the acetabulum between standardized AP pelvis radiography and hip-centered fluoroscopy.

Management of pelvic discontinuity in revision total hip arthroplasty: a review of the literature.

Pelvic discontinuity is a complex problem in revision total hip arthroplasty. Although rare, the incidence is likely to increase due to the ageing population and the increasing number of total hip arthroplasties being performed. The various surgical options available to solve this problem include plating, massive allografts, reconstruction rings, custom triflanged components and tantalum implants. However, the optimal solution remains controversial. None of the known methods completely solves the major obstacles associated with this problem, such as restoration of massive bone loss, implant failure in the short- and long-term and high complication rates. This review discusses the diagnosis, decision making, and treatment options of pelvic discontinuity in revision total hip arthroplasty.

The science of rotator cuff tears: translating animal models to clinical recommendations using simulation analysis.

PURPOSE: The purpose of this article is to review basic science studies using various animal models for rotator cuff research and to describe structural, biomechanical, and functional changes to muscle following rotator cuff tears. The use of computational simulations to translate the findings from animal models to human scale is further detailed. METHODS: A comprehensive review was performed of the basic science literature describing the use of animal models and simulation analysis to examine muscle function following rotator cuff injury and repair in the ageing population. RESULTS: The findings from various studies of rotator cuff pathology emphasize the importance of preventing permanent muscular changes with detrimental results. In vivo muscle function, electromyography, and passive muscle-tendon unit properties were studied before and after supraspinatus tenotomy in a rodent rotator cuff injury model (acute vs chronic). Then, a series of simulation experiments were conducted using a validated computational human musculoskeletal shoulder model to assess both passive and active tension of rotator cuff repairs based on surgical positioning. CONCLUSION: Outcomes of rotator cuff repair may be improved by earlier surgical intervention, with lower surgical repair tensions and fewer electromyographic neuromuscular changes. An integrated approach of animal experiments, computer simulation analyses, and clinical studies may allow us to gain a fundamental understanding of the underlying pathology and interpret the results for clinical translation.

A novel process for optimizing musculoskeletal allograft tissue to improve safety, ultrastructural properties, and cell infiltration.

BACKGROUND: This study evaluated the properties of scaffold derived from freeze-dried human Achilles tendon allograft for use in anterior cruciate ligament (ACL) reconstruction. Our hypothesis was that such an allograft could be processed using a method to remove cellular and infectious material, producing a cytocompatible, architecturally modified scaffold possessing tensile properties suitable for ACL reconstruction. METHODS: Fifty-two allografts were provided by a tissue bank. Twenty-one were used as controls to assess cellularity, DNA content, microarchitecture, porosity, cytocompatibility, and tensile properties in vitro (n = 13) and in vivo (n = 8). Thirty-one were processed to produce scaffolds that were similarly assessed for these properties in vitro (n = 23) and in vivo (n = 8). The elimination of added enveloped and nonenveloped viruses was also determined in vitro after each processing step. RESULTS: A subjective decrease in cellularity and a significant decrease in DNA content were observed in the scaffolds compared with the allografts from which they had been derived. The porosity was increased significantly, and the scaffolds were cytocompatible in vitro. Processing resulted in significantly increased elongation of the scaffolds (138% of the elongation of the unprocessed allograft) during tensile testing. No other significant differences in tensile properties were observed in vitro or in vivo. The number of infiltrating host cells and the depth to which those cells infiltrated were significantly greater in the scaffolds. No enveloped viruses and only two of 10(8) nonenveloped viruses were detected in the scaffolds after processing, corresponding to a sterility assurance level of 0.2 × 10(-7). CONCLUSIONS: Allografts were processed using a method that removed cellular and infectious material to produce a decellularized, cytocompatible, architecturally modified scaffold with tensile properties that differed minimally from those of human allograft tissue both in vitro and in vivo. The scaffold production process also resulted in an increase in porosity that led to increased cell infiltration in vivo.

Evaluation of in vivo rotator cuff muscle function after acute and chronic detachment of the supraspinatus tendon: an experimental study in an animal model.

BACKGROUND: Surgical repair of large chronic rotator cuff tears can be technically demanding because it requires manipulation of a muscle-tendon unit that is scarred, retracted, and stiffer than normal, all of which contribute to increased tension at the repair site. The purpose of the present study was to characterize the in vivo rotator cuff muscle-tendon unit function after acute and chronic injury at surgically relevant preload tensions. METHODS: Sixty-two Sprague-Dawley rats were divided into a healthy, uninjured (control) group (n = 22), an acute injury group (n = 20), and a chronic injury group (n = 20) and underwent in vivo muscle force testing and electromyographic testing of the supraspinatus muscle-tendon unit at various preload tensions. RESULTS: Preload tension affected the maximum supraspinatus muscle contractile force in all groups (p < 0.05). At the peak tension required to repair an acute tear, there was a 28% to 30% reduction in maximum tetanic contraction amplitude in all groups (p < 0.05). At the peak tension required to repair a chronic tear, there was a 40% to 53% reduction in maximal tetanic contraction amplitude in all groups (p < 0.05). The uninjured (control) group showed increased muscle endurance (p < 0.05) in comparison with the acute injury and chronic injury groups at all preload tensions. The chronic injury group showed reduced compound motor action potential amplitude (p < 0.05). CONCLUSIONS: Both the acute and chronic injury groups demonstrated functional impairment related to increasing preload tensions. Higher repair tensions, associated with the chronic injury setting, resulted in greater functional impairment. The present study also demonstrates an association between increased time from rotator cuff tendon injury and impaired in vivo rotator cuff muscle electromyographic findings.

An acellular, allograft-derived meniscus scaffold in an ovine model.

PURPOSE: The purpose of this study was to develop a meniscus scaffold that has increased porosity and maintains the native meniscus extracellular matrix in an ovine model. METHODS: The medial menisci of skeletally mature ovine (n = 16) were harvested; half were made into meniscus scaffolds (n = 8), and half remained intact (n = 8). Intact and scaffold meniscus tissues were compared by use of histology, DNA content analysis, in vitro cellular biocompatibility assays, and ultrastructural analysis. An additional 16 knees were used to investigate the biomechanics of the intact meniscus compared with the meniscus scaffold. RESULTS: DNA content and histology showed a significant decrease in cellular and nuclear content in the meniscus scaffold (P < .003). Biocompatibility was supported through in vitro cellular assays. Scanning electron microscopy and micro-computed tomography showed a substantial increase in porosity and pore connectivity in the meniscus scaffold compared with the intact meniscus (P < .01). There was no statistical difference between the ultimate load or elastic modulus of the intact and meniscus scaffolds. CONCLUSIONS: In this study a meniscus scaffold was evaluated for potential clinical application as a meniscus transplant construct in an ovine model. The data showed that a decellularized meniscus scaffold with increased porosity was comparable to the intact meniscus, with an absence of in vitro cellular toxicity. Although some compositional alterations of the extracellular matrix are to be expected during processing, it is evident that many of the essential structural components remained functional with maintenance of biomechanical properties. CLINICAL RELEVANCE: This meniscus scaffold has potential for future clinical application as a meniscus transplant construct.

A naturally derived, cytocompatible, and architecturally optimized scaffold for tendon and ligament regeneration.

Tissue-engineered tendon scaffolds have the potential to significantly improve the treatment of tendon and ligament injuries, especially those associated with tumors, trauma, and congenital deficiencies where autograft or allograft tissue might not be available in sufficient quantity for reconstruction. In this study, a tendon scaffold was produced that: (1) has decreased/absent cellular material histologically, as well as significantly decreased DNA content in comparison with the material it is derived from-fresh-frozen flexor digitorum profundus tendon; (2) is cytocompatible in vitro; (3) has been modified to produce increased pore size and porosity; (4) retains 76-78% of the tensile properties of the material it is derived from; (5) is readily infiltrated by fibroblast-like, mononuclear host cells; and (6) does not exhibit a host-cell-mediated foreign-body immune response after implantation in vivo.