scholarly journals Tough and tunable scaffold-hydrogel composite biomaterial for soft-to-hard musculoskeletal tissue interfaces

2020 ◽  
Vol 6 (34) ◽  
pp. eabb6763
Author(s):  
Raul A. Sun Han Chang ◽  
John F. Shanley ◽  
Mariana E. Kersh ◽  
Brendan A.C. Harley

Tendon inserts into bone via a fibrocartilaginous interface (enthesis) that reduces mechanical strain and tissue failure. Despite this toughening mechanism, tears occur because of acute (overload) or degradative (aging) processes. Surgically fixating torn tendon into bone results in the formation of a scar tissue interface with inferior biomechanical properties. Progress toward enthesis regeneration requires biomaterial approaches to protect cells from high levels of interfacial strain. We report an innovative tissue reinforcement strategy: a stratified scaffold containing osseous and tendinous tissue compartments attached through a continuous polyethylene glycol (PEG) hydrogel interface. Tuning the gelation kinetics of the hydrogel modulates integration with the flanking compartments and yields biomechanical performance advantages. Notably, the hydrogel interface reduces formation of strain concentrations between tissue compartments in conventional stratified biomaterials that can have deleterious biological effects. This design of mechanically robust stratified composite biomaterials may be appropriate for a broad range of tendon and ligament-to-bone insertions.

Author(s):  
Raul A. Sun Han Chang ◽  
Mariana E. Kersh ◽  
Brendan A.C. Harley

AbstractBiological interfaces connecting tissues with dissimilar mechanical and structural properties are ubiquitous throughout the musculoskeletal system. Tendons attach to bone via a fibrocartilaginous interface (enthesis) that reduces mechanical strain and resultant tissue failure. Despite this toughening mechanism, tears at the enthesis occur due to acute (overload) or degradative (aging) processes. Repair involves surgical fixation of the torn tendon to bone, but results in the formation of a narrow fibrovascular scar tissue with inferior biomechanical properties. Progress toward enthesis regeneration requires biomaterial approaches to protect exogenously added or endogenously recruited cells from high levels of strain at the interface between dissimilar materials. Here, we describe an innovative reinforcement strategy to address this need. We report a stratified scaffold containing collagen bone and tendon tissue compartments linked by a continuous polyethylene glycol (PEG) hydrogel interface. Tuning the gelation kinetics of the hydrogel modulates its integration with the surrounding biomaterial compartments and yields biomechanical performance advantages. Notably, the continuous hydrogel interface reduces the deleterious effects of strain concentrations that form between tissue compartments in conventional stratified biomaterials. This design of mechanically robust stratified composite biomaterials may be appropriate for a broad range of tendon and ligament-to-bone insertions.


1997 ◽  
Vol 470 ◽  
Author(s):  
Patricia Warren ◽  
Stephane Retzmanick ◽  
Martin Gotza ◽  
Marc Begems

ABSTRACTSi / Si1-x-yGexCy / Si heterostructures containing up to 17 at.% Ge and 1.9 at.% C were grown on (001) silicon by low pressure Rapid Thermal Chemical Vapor Deposition, using a mixture of silane, germane and methylsilane, diluted in hydrogen. The samples were then annealed in a Rapid Thermal Processing furnace, under an atmospheric pressure of nitrogen, at temperatures ranging from 900 to 1130 °C.The samples were characterized using infrared spectroscopy and x-ray diffraction. SIMS profiling and TEM observation were performed on some of the samples.Substitutional C gradually disappeared, either precipitating out to form cubic silicon carbide (β-SiC), or simply vanishing into interstitial positions. In any case, the in-plane lattice constant remained constant after annealing, indicating that there was no mechanical strain relaxation by formation of misfit dislocations. The perpendicular lattice constant increased due to the decrease in substitutional C concentration, as well as it decreased due to the germanium out-diffusion. This variation of the strain during annealing was modeled, and allowed the determination of the kinetics of the substitutional carbon disappearance. The same behavior was observed for all samples. Indeed, the Cs disappearance rate was always increased for samples with higher initial Ge and C concentrations. The kinetics of this precipitation was found in very good agreement with previous published results.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Elena Stocco ◽  
Silvia Barbon ◽  
Daniele Dalzoppo ◽  
Silvano Lora ◽  
Leonardo Sartore ◽  
...  

Articular cartilage lesions are a particular challenge for regenerative medicine due to cartilage low self-ability repair in case of damage. Hence, a significant goal of musculoskeletal tissue engineering is the development of suitable structures in virtue of their matrix composition and biomechanical properties. The objective of our study was to designin vitroa supporting structure for autologous chondrocyte growth. We realized a biohybrid composite scaffold combining a novel and nonspecific extracellular matrix (ECM), which is decellularized Wharton’s jelly ECM, with the biomechanical properties of the synthetic hydrogel polyvinyl alcohol (PVA). Wharton’s jelly ECM was tested for its ability in promoting scaffold colonization by chondrocytes and compared with polyvinyl alcohol itself and the more specific decellularized cartilage matrix. Our preliminary evidences highlighted the chance of using Wharton’s jelly ECM in combination with PVA hydrogels as an innovative and easily available scaffold for cartilage restoration.


2001 ◽  
Vol 2 (2) ◽  
pp. 40-41
Author(s):  
L.D. Cudmore ◽  
F.M. Riches ◽  
P.H.R. Barrett ◽  
S. Song ◽  
G.F. Watts

Author(s):  
V. V. Skarga ◽  
E. V. Nevezhin ◽  
A. А. Matrosov ◽  
V. V. Negrebetsky ◽  
M. V. Malakhov

Photooxidized psoralen solutions possess a variety of biological effects, which implementation mechanism may presumably involve hydroperoxides. Here, the hydroperoxide content in photooxidized psoralen solutions was assessed using photometric FOX assay (from Ferrous Oxidation + Xylenol Orange). FOX reagent with 10× content of Xylenol Orange, modified for quantitative analysis of up to 50 μM of hydroperoxides in aqueous phase was used in experiments. During photooxidation of 0.1 mM psoralen in phosphate buffer solution, hydroperoxide production increases with dose of UVA irradiation (~2.5 μM eq. of H2O2 for dose of 252 kJ/m2 and ~11 μM eq. of H2O2 for dose of 1512 kJ/m2) and reaches ~16.5 μM eq. of H2O2 at the highest dose investigated (3024 kJ/m2). A comparison of kinetics of psoralen photolysis and hydroperoxide generation allows us to suggest that generation of hydroperoxide results from the secondary photochemical processes involving psoralen photoproducts, presumably from photoinduced autooxidation of aldehydic photoproducts of psoralen.


Author(s):  
Massimo A. Fazio ◽  
Rafael Grytz ◽  
Jeffrey S. Morris ◽  
Luigi Bruno ◽  
Christopher A. Girkin ◽  
...  

In glaucoma, the optic nerve head (ONH) is the site of damage to the retinal ganglion cell axons that transmit the visual information from the eye to the brain. Results of several randomized prospective trials showed that intraocular pressure (IOP), age 1, increased optic disc cupping, corneal thickness, and African ancestry 2 are independently associated with glaucomatous progression. All of these risk factors have a biologically plausible association with either the level of IOP, the severity of disease, or biomechanical properties of the ONH. Importantly, age is the only risk factor other than IOP that is independently associated with the onset and progression of glaucoma across all of the major prospective clinical trials conducted over the past twenty years. In addition, every population-based survey conducted to date has demonstrated a strong relationship between the prevalence of glaucoma with advancing age, despite almost no studies showing IOP changes with age. These findings indicate that the aging ONH becomes increasingly vulnerable to glaucomatous injury at similar levels of IOP.


Author(s):  
Brendan A. C. Harley

Tendons are specialized connective tissues that transmit load between bone and muscle, and whose microstructural and compositional features underlie their function. The biological solution to the problem of connecting relatively compliant tendon to stiffer (∼2 orders of magnitude) bone is a gradient interface zone ∼100μm wide. Over the tendon-bone-junction (TBJ) a linear transition takes place in the ECM inorganic:organic (mineral:collagen) ratio as well as mineral crystallinity from that of tendon to bone. While small TBJ injuries can heal via regeneration, severe defects undergo repair-mediated healing characterized by fibrocartilagenous scar tissue with inferior biomechanical and functional properties. Severe TBJ injuries are common in athletes, the elderly, and following severe craniofacial and extremity trauma. Many tendon injuries (i.e. supraspinatus injuries), particularly those associated with acute trauma, are prone to occur at the TBJ due to high levels of region-specific stress concentrations; rotator cuff tendons injuries, one of the most common TBJ injuries, exhibit re-tears at rates as high as 94%. The scale of such defects and current poor clinical results suggest the need for a biomaterial solution that can mimic the dynamic heterogeneities of the native insertion and tendon body to induce rapid, functional regeneration. Three-dimensional collagen-GAG (CG) scaffolds have been successfully used clinically to regenerate large soft tissue defects (skin, peripheral nerves); they act by mimicking the native extracellular matrix (ECM) of the damaged tissue to prevent wound contraction and scar tissue synthesis. However these scaffolds have not traditionally been used for orthopedics due to an inability to recapitulate two critical features of orthopedic tissues: multiscale structural complexity, biomechanical properties. While the multi-scale properties of tendon itself cannot be currently replicated, nature provides an alternative paradigm: core-shell composites. Plant stems combine a porous core with a dense shell to aid osmotic transport (core) while maintaining sufficient tensile/bending stiffness (shell); many bird beaks use core-shell designs to efficiently enhance compressive strength. Here we describe development of three biomaterial engineering approaches to create the next generation of regeneration templates for tendon insertion injuries: composite, spatially patterned CG biomaterials.


2017 ◽  
Vol 5 (4_suppl4) ◽  
pp. 2325967117S0015
Author(s):  
Isabel Faust ◽  
Philipp Traut ◽  
Cornelius Knappe ◽  
Doris Hendig

Aims and Objectives: Arthrofibrosis is defined as painful impairment of joint flexibility due to fibrotic tissue remodeling after joint trauma or surgery. The incidence of arthrofibrosis after knee replacement surgery is 5 to 10%. Although conventional therapeutic approaches as for instance mobilization and physiotherapy are applied, an effective and causative therapeutic regimen is not known. Materials and Methods: To characterize arthrofibrotic remodeling of the extracellular matrix, to develop new therapeutic approaches and to define diagnostic biomarkers and therapeutic targets, understanding of biochemical principles is urgently required. Fibrotic remodeling was described in several tissues, whereas synovial fibrosis is one of the least investigated fibrotic disorders. Nevertheless, molecular key events in fibrosis seem to be the same and are initiated by exogenic or endogenic tissue damage and differentiation of resident fibroblasts of the connective tissue to myofibroblasts. Known inductors of myofibroblast differentiation are fibrotic growth factors, which are secreted by platelets, damaged tissue and inflammatory cells, as well as mechanical strain. Research studies concerning cardiac fibrosis in tako-tsubo cardiomyopathy also define emotional stress and sympathicotonic destabilization as profibrotic stressors. Myofibroblasts generate contractile forces and synthesize extracellular matrix components, so that scar tissue accumulates. While myofibroblasts disappear by apoptosis in physiological wound healing, they persist in fibrosis. Results: Recently, we could demonstrate that increased expression of human xylosyltransferase (XT)-I, an enzyme which catalyzes the rate limiting step in proteoglycan glycosylation, is linked to abnormal extracellular matrix remodeling. Serum XT activity reflects proteoglycan synthesis rate and is known as fibrosis biomarker in liver fibrosis or scleroderma. Our data also indicate that XT-I is a cellular key mediator of arthrofibrosis. However, we suggest that molecular changes based on arthrofibrosis are, due to local restriction of the affected joint by the blood-synovial-barrier, not detectable in human serum. Currently, we study synovial XT activity of arthrofibrosis patients and controls in a multicenter study. Conclusion: In summary, we give insights into the complex pathobiochemistry of arthrofibrosis as well as current research projects. A deeper characterization of the involved mechanisms might not only contribute to control and inhibit fibrotic remodeling by interfering with components of fibrotic signal cascades but also to establish new therapeutic strategies.


1974 ◽  
Vol 137 (2) ◽  
pp. 313-317 ◽  
Author(s):  
Kenneth V. Shooter ◽  
Ruth Howse ◽  
R. Kenneth Merrifield

The extent of biological inactivation and of the degradation of the RNA after reaction of bacteriophage R17 with ethyl methanesulphonate, isopropyl methanesulphonate and N-ethyl-N-nitrosourea was studied. Formation of breaks in the RNA chain probably results from hydrolysis of phosphotriesters formed in the alkylation reactions. Near neutral pH the ethyl and isopropyl phosphotriesters are sufficiently stable for the kinetics of the hydrolysis reaction to be followed. Results indicate that the rate of hydrolysis increases rapidly as the pH is raised. The evidence shows that a phosphotriester group does not itself constitute a lethal lesion. The extent of phosphotriester formation by the different agents is discussed in terms of reaction mechanism.


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