Augmentation of Rotator Cuff Repair With Soft Tissue Scaffolds

Background Tears of the rotator cuff are one of the most common tendon disorders. Treatment often includes surgical repair, but the rate of failure to gain or maintain healing has been reported to be as high as 94%. This has been substantially attributed to the inadequate capacity of tendon to heal once damaged, particularly to bone at the enthesis. A number of strategies have been developed to improve tendon-bone healing, tendon-tendon healing, and tendon regeneration. Scaffolds have received considerable attention for replacement, reconstruction, or reinforcement of tendon defects but may not possess situation-specific or durable mechanical and biological characteristics. Purpose To provide an overview of the biology of tendon-bone healing and the current scaffolds used to augment rotator cuff repairs. Study Design Systematic review; Level of evidence, 4. Methods A preliminary literature search of MEDLINE and Embase databases was performed using the terms rotator cuff scaffolds, rotator cuff augmentation, allografts for rotator cuff repair, xenografts for rotator cuff repair, and synthetic grafts for rotator cuff repair. Results The search identified 438 unique articles. Of these, 214 articles were irrelevant to the topic and were therefore excluded. This left a total of 224 studies that were suitable for analysis. Conclusion A number of novel biomaterials have been developed into biologically and mechanically favorable scaffolds. Few clinical trials have examined their effect on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups. While there is still considerable work to be done before scaffolds are introduced into routine clinical practice, there does appear to be a clear indication for their use as an interpositional graft for large and massive retracted rotator cuff tears and when repairing a poor-quality degenerative tendon

Supraspinatus detachment causes musculotendinous degeneration and a reduction in bone mineral density at the enthesis in a rat model of chronic rotator cuff degeneration

BACKGROUND: To evaluate biological strategies that enhance tendon-bone healing in humans, it is imperative that suitable animal models accurately reproduce the pathological changes observed in the clinical setting following a tear. The purpose of the present study was to investigate rotator cuff degeneration in a rat, as well as assess the development of osteopenia at the enthesis following tendon detachment. METHODS: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Specimens were retrieved at 4 weeks (n = 6), 6 weeks (n = 6) and 9 weeks (n = 6) postoperatively for histological analysis and peripheral quantitative computer tomography. RESULTS: Three weeks following tendon detachment, there was a significant increase in the modified Movin score, characterized by a loss of muscle mass, fatty infiltration, an increase in musculotendinous cellularity, loss of normal collagen fibre structure/arrangement, rounded tenocyte nuclei and an increase in the number of vascular bundles. This was accompanied by a reduction in bone mineral density at the tendon insertion site. After 3 weeks however, these changes were less prominent. CONCLUSIONS: The rotator cuff tendon-muscle-bone unit in a rat model 3 weeks after detachment of supraspinatus represents a valid model for investigating rotator cuff degeneration

Intraosseous transcutaneous amputation prostheses vs dental implants: A comparison between keratinocytes and gingival cell adhesion in vitro.

Keratinocytes versus gingival cell adhesion European Cells and Materials Vol. 29 2015 (pages 237-249) ISSN 1473-2262 Abstract Infection is the primary failure modality for transcutaneous implants because the skin breach provides a route for pathogens to enter the body. Intraosseous transcutaneous amputation prostheses (ITAP) are being developed to overcome this problem by creating a seal at the skin-implant interface. Oral gingival epithelial cell attachment creates an infection-free seal around dental implants. However, this has yet to be achieved consistently outside of the oral environment. Epithelial cells attach to metal substrates by means of hemidesmosomes and focal adhesions. Their density per unit cell is an indicator of attachment strength. We postulate that gingival epithelial cells express more hemidesmosomes and focal adhesions at earlier time points, compared with epidermal keratinocytes, and this increased speed and strength of attachment may be the reason why an infection-free seal is often achieved around dental implants but less frequently around ITAP. The aim of this study was to compare epidermal keratinocyte with oral gingival cell attachment on titanium alloy in vitro, to determine whether these two cell types differ in their speed and strength of attachment. We aimed to test the hypothesis that gingival cells up-regulate focal adhesion and hemidesmosome formation at earlier time points compared with extra-oral keratinocytes. To test this hypothesis we cultured epidermal keratinocytes and oral gingival cells on titanium alloy substrates and assessed cell attachment by focal adhesions and hemidesmosome expression at 4, 24, 48 and 72 hours. Formation and expression of hemidesmosomes temporally lagged behind that of focal adhesions in both cell types. Gingival derived cells up-regulated focal adhesion and hemidesmosome expression at earlier time points compared with epidermal keratinocytes. Hemidesmosome expression in oral gingival cells was 3 times greater compared with epidermal keratinocytes at 4 hours. Our findings indicate that earlier attachment may be key to the success of the dental implant transcutaneous interface

Application of a Demineralized Cortical Bone Matrix and Bone Marrow-Derived Mesenchymal Stem Cells in a Model of Chronic Rotator Cuff Degeneration

BACKGROUND: The success of rotator cuff repair is primarily dependent on tendon-bone healing. Failure is common because weak scar tissue replaces the native enthesis, rendering it prone to reruptures. A demineralized bone matrix (DBM) consists of a network of collagen fibers that provide a sustained release of growth factors such as bone morphogenetic proteins. Previous studies have demonstrated that it can regenerate a fibrocartilaginous enthesis. HYPOTHESIS: The use of a DBM and mesenchymal stem cells (MSCs) at the healing enthesis will result in a higher bone mineral density at the tendon insertion and will enhance the regeneration of a morphologically superior enthesis when compared with an acellular human dermal matrix. STUDY DESIGN: Controlled laboratory study. METHODS: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Three weeks later, tendon repair was carried out in animals randomized into 3 groups: group 1 received augmentation of the repair with a cortical allogenic DBM (n = 6); group 2 received augmentation with a nonmeshed, ultrathick, acellular human dermal matrix (n = 6); and group 3 underwent tendon-bone repair without a scaffold (n = 6). All animals received 1 × 10(6) MSCs delivered in fibrin glue to the repair site. Specimens were retrieved at 6 weeks postoperatively for histological analysis and the evaluation of bone mineral density. RESULTS: All groups demonstrated closure of the tendon-bone gap with a fibrocartilaginous enthesis. Although there were no significant differences in the enthesis maturation and modified Movin scores, repair augmented with a dermal matrix + MSCs exhibited a disorganized enthesis, abnormal collagen fiber arrangement, and greater cellularity compared with other MSC groups. Only repairs augmented with a DBM + MSCs reached a bone mineral density not significantly lower than nonoperated controls. CONCLUSION: A DBM enhanced with MSCs can augment rotator cuff healing at 6 weeks and restore bone mineral density at the enthesis to its preinjury levels. CLINICAL RELEVANCE: Biological augmentation of rotator cuff repair with a DBM and MSCs may reduce the incidence of retears, although further studies are required to determine its effectiveness

The effectiveness of demineralized cortical bone matrix in a chronic rotator cuff tear model.

BACKGROUND: The purpose of this study was to assess the effect of demineralized bone matrix (DBM) on rotator cuff tendon-bone healing. The hypothesis was that compared with a commercially available dermal matrix scaffold, DBM would result in a higher bone mineral density and regenerate a morphologically superior enthesis in a rat model of chronic rotator cuff degeneration. METHODS: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Three weeks later, tendon repair was carried out in animals randomized into 3 groups: group 1 animals were repaired with DBM (n = 6); group 2 received augmentation with the dermal scaffold (n = 6); and group 3 (controls) underwent nonaugmented tendon-bone repair (n = 6). Specimens were retrieved at 6 weeks postoperatively for histologic analysis and evaluation of bone mineral density. RESULTS: No failures of tendon-bone healing were noted throughout the study. All groups demonstrated closure of the tendon-bone gap with a fibrocartilaginous interface. Dermal collagen specimens exhibited a disorganized structure with significantly more abnormal collagen fiber arrangement and cellularity than in the DBM-based repairs. Nonaugmented repairs exhibited a significantly higher bone mineral density than in DBM and the dermal collagen specimens and were not significantly different from control limbs that were not operated on. CONCLUSION: The application of DBM to a rat model of chronic rotator cuff degeneration did not improve the composition of the healing enthesis compared with nonaugmented controls and a commercially available scaffold. However, perhaps the most important finding of this study was that the control group demonstrated a similar outcome to augmented repairs

The mechanical strength of additive manufactured intraosseous transcutaneous amputation prosthesis, known as the ITAP

The focus of this research is the ability to manufacture, when using layer base production methods, the medical insert known as ITAP used for prosthetic attachment in a femur. It has been demonstrated using computational modelling that a 3-dimensional build of the ITAP has the lowest stress present when the honeycomb infill pattern’s percentage is set at 100%, with the ITAP being constructed on a horizontal printing bed with the shear forces acting adjacent to the honeycomb structure. The testing has followed the British standard ISO 527-2:2012, which shows a layer base printed tensile test sample, with a print setting of 100% infill and at a side print orientation; this was found to withstand a greater load before failure than any other printed test configuration. These findings have been validated through simulations that analyses the compression, shear and torque forces acting upon an augmented femur, with an imbedded ITAP model

Molecular Identification and Expression Analysis of Filaggrin-2, a Member of the S100 Fused-Type Protein Family

Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions. Recent genetic studies have shown that mutations within the gene encoding the SFTP filaggrin cause ichthyosis vulgaris and are major predisposing factors for atopic dermatitis. As a vital component of healthy skin, filaggrin is also a precursor of natural moisturizing factors. Here we present the discovery of a member of this family, designated as filaggrin-2 (FLG2) that is expressed in human skin. The FLG2 gene encodes a histidine- and glutamine-rich protein of approximately 248 kDa, which shares common structural features with other SFTP members, in particular filaggrin. We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta. In cultured primary keratinocytes, FLG2 mRNA expression displayed almost the same kinetics as that of filaggrin following Ca2+ stimulation, suggesting an important role in molecular regulation of epidermal terminal differentiation. We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis. Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors