Observation of Collagen-Containing Lesions After Hematoma Resolution in Intracerebral Hemorrhage.

Background and Purpose: The classic presentation of chronic (stage III) hemorrhagic stroke lesions is a fluid-filled cavity. In one of the most commonly used animal models of intracerebral hemorrhage (ICH), we noticed additional solid material within the chronic lesion. We examined the composition of those chronic ICH lesions and compared them with human autopsy cases. Methods: ICH was induced in rats by the injection of collagenase in the striatum. Tissue sections after hematoma resolution corresponding to 3 different chronic time points­28, 42, and 73 to 85 days post-ICH­were selected. Human autopsy reports at the University Hospital of Zurich were searched between 1990 and 2019 for ICH, and 3 chronic cases were found. The rat and human sections were stained with a variety of histopathologic markers. Results: Extensive collagenous material was observed in the chronic lesion after hematoma resolution in both the rat model and human autopsy cases. Additional immunostaining revealed that the material consisted primarily of a loose network of collagen 3 intermingled with occasional GFAP (glial fibrillary acidic protein)-positive processes and collagen 4. Conclusions: A key feature of the chronic ICH lesion is a loose network of collagen 3. The collagenase rat model reproduces the morphology and composition of the chronic human ICH lesion. While identifying new features of ICH lesion pathology, these results are important for treatment and recovery strategies.

Extracorporeal Shock Wave Stimulates Angiogenesis and Collagen Production in Facial Soft Tissue.

BACKGROUND: This study investigated the efficacy of extracorporeal shock wave (ESW) application in stimulating dermal thickness, vascularity, and collagen synthesis of facial skin in a large animal model. MATERIALS AND METHODS: The facial skin of the maxillary and mandibular areas of goats (n = 6 per group) was treated with ESWs of different intensities (0.15 and 0.45 mJ/mm2; 1000 pulses). After 4 d, histology and immunohistochemistry were used to evaluate the following: dermal thickness, total number and abundance of microvessels, amount of type 1 collagen, and α-smooth muscle actin expression. RESULTS: Dermal thickness, number and abundance of microvessels, and collagen synthesis increased after ESW application at both intensities (each P < 0.05). When comparing ESW groups, the highest collagen abundance was seen after 0.15 mJ/mm2 (P = 0.034), whereas the highest number of microvessels was detected after treatment with 0.45 mJ/mm2 (P = 0.002). CONCLUSIONS: A single-session application of focused low-energy ESWs to facial skin can increase dermal thickness by stimulating collagen production and local microcirculation. These findings commend the technique for future investigation for pretreatment of local or microvascular skin flaps to enhance tissue healing.

No effect of topical application of tranexamic acid on articular cartilage.

PURPOSE: The objective of this study was to evaluate potential cytotoxicity of TXA on articular cartilage by assessing chondrocyte viability of osteochondral explants after exposure to different concentrations and durations of TXA. METHODS: Thirty-nine osteochondral plugs (OCPs) were harvested from three adult Yucatan minipigs immediately after their death. OCPs were divided into 13 groups exposed to different concentrations of TXA (1, 2 and 4 mg/ml in saline solution) for 1, 3 and 6 h. Negative controls were exposed to saline solution for 0, 1, 3 and 6 h. Chondrocyte viability was assessed by Live/Dead cell assay and calculated as the ratio of live cells (green fluorescence) to overall cells (green + red cells) for each concentration of TXA and time point in a 50-µm scanned image. RESULTS: No correlation was found between chondrocyte viability, and TXA concentration and time of exposure. Overall, chondrocyte viability ranged from 90 to 99%. There was no statistical difference among control group, 1, 2 and 4 mg/ml TXA solutions at each time point [1 h (n.s.), 3 h (n.s.), 6 h (n.s.)]. Similarly, no statistical difference among groups was observed when comparing cell viability at 1, 3 and 6 h of TXA exposure, (Fig. 2) [1 mg/ml (n.s.), 2 mg/ml (n.s.), and 4 mg/ml (n.s.)]. CONCLUSIONS: In conclusion, doses of TXA approximating the current clinical protocols for topical use did not demonstrate any cytotoxic effects on cartilage explants in a Yucatan mini pig model. Thus, supporting the topical application for procedures with intact cartilage, such as partial knee replacement surgery and cartilage repair procedures.

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction.

Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration.

Ectoderm mesenchymal stem cells promote differentiation and maturation of oligodendrocyte precursor cells.

Many neurological diseases are closely associated with demyelination caused by pathological changes of oligodendrocytes. Although intrinsic remyelination occurs after injury, the regeneration efficiency of myelinating oligodendrocytes remains to be improved. Herein, we reported an initiative finding of employing a valuable cell source, namely neural crest-derived ectoderm mesenchymal stem cells (EMSCs), for promoting oligodendrocyte differentiation and maturation by co-culturing oligodendrocyte precursor cells (OPCs) with the EMSCs. The results demonstrated that the OPCs/EMSCs co-culture could remarkably increase the number and length of oligodendrocyte processes in comparison with the mono-cultured OPCs and non-contact OPCs/EMSCs transwell culture. Furthermore, the inhibition experiments revealed that the EMSCs-produced soluble factor Sonic hedgehog, gap junction protein connexin 43 and extracellular matrix molecule laminin accounted for the promoted OPC differentiation since inhibiting the function of anyone of the three proteins led to substantial retraction of processes and detachment of oligodendrocytes. Altogether, OPCs/EMSCs co-culture system could be a paradigmatic approach for promoting differentiation and maturation of oligodendrocytes, and EMSCs will be a promising cell source for the treatment of neurological diseases caused by oligodendrocyte death and demyelination.

Cellular senescence in aging and osteoarthritis.

- It is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Cellular senescence, the loss of the ability of cells to divide, has been noted as the major factor contributing to age-related changes in cartilage homeostasis, function, and response to injury. The underlying mechanisms of cellular senescence, while not fully understood, have been associated with telomere erosion, DNA damage, oxidative stress, and inflammation. In this review, we discuss the causes and consequences of cellular senescence, and the associated biological challenges in cartilage repair. In addition, we present novel strategies for modulation of cellular senescence that may help to improve cartilage regeneration in an aging population.

Aarhus Regenerative Orthopaedics Symposium (AROS).

The combination of modern interventional and preventive medicine has led to an epidemic of ageing. While this phenomenon is a positive consequence of an improved lifestyle and achievements in a society, the longer life expectancy is often accompanied by decline in quality of life due to musculoskeletal pain and disability. The Aarhus Regenerative Orthopaedics Symposium (AROS) 2015 was motivated by the need to address regenerative challenges in an ageing population by engaging clinicians, basic scientists, and engineers. In this position paper, we review our contemporary understanding of societal, patient-related, and basic science-related challenges in order to provide a reasoned roadmap for the future to deal with this compelling and urgent healthcare problem.

Chemotactic recruitment of adult neural progenitor cells into multifunctional hydrogels providing sustained SDF-1α release and compatible structural support.

Without chemotactic cues and structural support, cavitary brain lesions typically fail to recruit endogenous neural progenitor cells (NPCs). Toward resolving this, we engineered multifunctional biomaterials comprising injectable gelatin-hydroxyphenylpropionic acid (Gtn-HPA) hydrogels and dextran sulfate/chitosan polyelectrolyte complex nanoparticles (PCNs) that delivered stromal cell-derived factor-1α (SDF-1α). Over 7 d of interface with in vitro tissue simulant containing adult rat hippocampal NPCs (aNPCs) and their neuronal progeny, Gtn-HPA/SDF-1α-PCN hydrogels promoted chemotactic recruitment to enhance infiltration of aNPCs by 3- to 45-fold relative to hydrogels that lacked SDF-1α or vehicles to sustain SDF-1α release. When cross-linked with 0.85-0.95 mM HO, Gtn-HPA/SDF-1α-PCN hydrogels provided optimally permissive structural support for migration of aNPCs. Specific matrix metalloproteinase (MMP) inhibitors revealed that 42, 30, and 55% of cell migration into Gtn-HPA/SDF-1α-PCN hydrogels involved MMP-2, 3, and 9, respectively, demonstrating the hydrogels to be compatible toward homing endogenous NPCs, given their expression of similar MMPs. Interestingly, PCNs utilized FGF-2 found in situ to induce chemokinesis, potentiate SDF-1α chemotactic recruitment, and increase proliferation of recruited cells, which collectively orchestrated a higher number of migrated aNPCs. Overall, Gtn-HPA/SDF-1α-PCN hydrogels prove to be promising biomaterials for injection into cavitary brain lesions to recruit endogenous NPCs and enhance neural tissue repair/regeneration.

Mechano-Chemical Effect of Gelatin- and HA-Based Hydrogels on Human Retinal Progenitor Cells.

Engineering matrices for cell therapy requires design criteria that include the ability of these materials to support, protect and enhance cellular behavior in vivo. The chemical and mechanical formulation of the biomaterials can influence not only target cell phenotype but also cellular differentiation. In this study, we have demonstrated the effect of a gelatin (Gtn)-hyaluronic acid (HA) hydrogel on human retinal progenitor cells (hRPCs) and show that by altering the mechanical properties of the materials, cellular behavior is altered as well. We have created an interpenetrating network polymer capable of encapsulating hRPCs. By manipulating the stiffness of the hydrogel, the differentiation potential of the hRPCs was controlled. Interpenetrating network 75 (IPN 75; 75% HA) allowed higher expression of rod photoreceptor markers, whereas cone photoreceptor marker expression was found to be higher in IPN 50. In vivo testing of these living matrices performed in Long-Evans rats showed higher levels of rod photoreceptor marker expression when IPN 75 was injected versus IPN 50. These biomaterials mimic biological cues that are required to simulate the dynamic complexity of natural retinal ECM. These hydrogels can be used as a vehicle for cell delivery in vivo as well as for expansion and differentiation in an in vitro 3D system in a highly reproducible manner.

Platelet-Rich Plasma Lysate-Incorporating Gelatin Hydrogel as a Scaffold for Bone Reconstruction.

In implant dentistry, large vertical and horizontal alveolar ridge deficiencies in mandibular and maxillary bone are challenges that clinicians continue to face. One of the limitations of porous blocks for reconstruction of bone in large defects in the oral cavity, and in the musculoskeletal system, is that fibrin clot does not adequately fill the interior pores and does not persist long enough to accommodate cell migration into the center of the block. The objective of our work was to develop a gelatin-based gel incorporating platelet-rich plasma (PRP) lysate, to mimic the role that a blood clot would normally play to attract and accommodate the migration of host osteoprogenitor and endothelial cells into the scaffold, thereby facilitating bone reconstruction. A conjugate of gelatin (Gtn) and hydroxyphenyl propionic acid (HPA), an amino-acid-like molecule, was commended for this application because of its ability to undergo enzyme-mediated covalent cross-linking to form a hydrogel in vivo, after being injected as a liquid. The initiation and propagation of cross-linking were under the control of horseradish peroxidase and hydrogen peroxide, respectively. The objectives of this in vitro study were directed toward evaluating: (1) the migration of rat mesenchymal stem cells (MSCs) into Gtn-HPA gel under the influence of rat PRP lysate or recombinant platelet-derived growth factor (PDGF)-BB incorporated into the gel; (2) the differentiation of MSCs, incorporated into the gel, into osteogenic cells under the influence of PRP lysate and PDGF-BB; and (3) the release kinetics of PDGF-BB from gels incorporating two formulations of PRP lysate and recombinant PDGF-BB. Results: The number of MSCs migrating into the hydrogel was significantly (3-fold) higher in the hydrogel group incorporating PRP lysate compared to the PDGF-BB and the blank gel control groups. For the differentiation/osteogenesis assay, the osteocalcin-positive cell area percentage was significantly higher in both the gel/PRP and gel/PDGF-BB groups, compared to the two control groups: cells in the blank gels grown in cell expansion medium and in osteogenic medium. Results of the ELISA release assay indicated that Gtn-HPA acted as an effective delivery vehicle for the sustained release of PDGF-BB from two different PRP lysate batches, with about 60% of the original PDGF-BB amount in the two groups remaining in the gel at 28 days. Conclusions: Gtn-HPA accommodates MSC migration. PRP-lysate-incorporating hydrogels chemoattract increased MSC migration into the Gtn-HPA compared to the blank gel. PRP-lysate- and the PDGF-BB-incorporating gels stimulate osteogenic differentiation of the MSCs. The release of the growth factors from Gtn-HPA containing PRP lysate can extend over the period of time (weeks) necessary for bone reconstruction. The findings demonstrate that Gtn-HPA can serve as both a scaffold for cell migration and a delivery vehicle that allows sustained and controlled release of the incorporated therapeutic agent over extended periods of time. These findings commend Gtn-HPA incorporating PRP lysate for infusion into porous calcium phosphate blocks for vertical and horizontal ridge reconstruction, and for other musculoskeletal applications.

Extracorporeal shockwave-induced expression of lubricin in tendons and septa.

Lubricin, a lubricating glycoprotein that facilitates tendon gliding, is upregulated by mechanical as well as biochemical stimuli, prompting this study of its induction by extracorporeal shockwave therapy (ESWT). The objective of this study was to characterize and quantify the effect of ESWT on lubricin expression in tendons and septa in a rat model. Hindlimbs of six rats were treated with low-dose ESWT and those of another six with high-dose ESWT, using contralateral limbs as controls. After 4 days, resected samples were processed for immunolocalization of lubricin using a purified monoclonal antibody. ESWT was found to increase lubricin expression in both low-dose and high-dose ESWT-treated tendons and also in septa. Lubricin expression generally increased with increasing dose of ESWT. Increased lubricin expression may contribute to the beneficial effects of ESWT in providing pain and symptom relief in musculoskeletal disorders by decreasing erosive wear.

Presence and distribution of the lubricating protein, lubricin, in the meibomian gland in rabbits.

PURPOSE: Lubricin is a principal boundary lubricating and anti-adhesion protein found in synovial fluid and several musculoskeletal tissues. This study investigates the presence of lubricin in the meibomian gland, lacrimal gland and ocular surface of healthy rabbits; prompted by the hypothesis that lubricin acts as boundary lubricant and anti-adhesive protein in the eye. METHODS: Thirty six eyelids were resected from ten cadaveric New Zealand White rabbits and two eyeballs and two lacrimal glands from two of them. Thirty two samples from 8 animals were processed for immunohistochemical localization of lubricin using a purified monoclonal antibody and quantification of the lubricin-containing meibocytes. Confirmatory western blot analysis was performed on four eyelids from 2 animals. RESULTS: Lubricin-positive meibomian cells were seen in the glands in all eight animals evaluated immunohistochemically. The percentage of lubricin-positive cells ranged from was 8%-50% in the upper and 3%-50% in the lower eyelid, with no significant difference between the upper and lower eyelid. Western blot analysis confirmed the presence of lubricin ranging from 10 to 40 ng in four eyelids from the other two rabbits. Occasional staining was seen in the epithelium of the hair follicles of the eyelid. No lubricin was evident on the ocular surface or in the lacrimal gland. CONCLUSIONS: Lubricin is secreted by the meibomian gland. The results provide a basis for the hypothesis that lubricin plays a role in boundary lubrication and in preventing adhesions in the eye, as well as in contributing to other functions of the meibomian gland. Moreover, if lubricin functions to decrease the friction between the eyelid and ocular surface, this study provides a rationale to supplement the amount of lubricin in cases of compromised meibomian gland function and other conditions.

Biomaterial-mediated delivery of microenvironmental cues for repair and regeneration of articular cartilage.

Articular cartilage injuries are one of the most challenging problems in musculoskeletal medicine due to the poor intrinsic regenerative capacity of this tissue. The lack of efficient treatment modalities motivates research into tissue engineering: combining cells, biomaterials mimicking extracellular matrix (scaffolds) and microenvironmental signaling cues. The aim of this review is to focus on the use of biomaterials as delivery systems for microenvironmental cues in relation to their applications for treatment of cartilage defects. The latest advances in cartilage tissue engineering and regeneration are critically reviewed to demonstrate an outline of challenges toward biomaterial-based approaches of cartilage regeneration.

An Injectable Multifunctional Dual-Phase Bead-Reinforced Gelatin Matrix Permissive of Mesenchymal Stem Cell Infiltration for Musculoskeletal Soft Tissue Repair.

This study develops a novel strategy for regenerative therapy of musculoskeletal soft tissue defects using a dual-phase multifunctional injectable gelatin-hydroxyphenyl propionic acid (Gtn-HPA) composite. The dual-phase gel consists of stiff, degradation-resistant, ≈2-mm diameter spherical beads made from 8 wt% Gtn-HPA in a 2 wt% Gtn-HPA matrix. The results of a 3D migration assay show that both the cell number and migration distance in the dual-phase gel system are comparable with the 2 wt% mono-phase Gtn-HPA, but notably significantly higher than for 8 wt% mono-phase Gtn-HPA (into which few cells migrated). The results also show that the dual phase gel system has degradation resistance and a prolonged growth factor release profile comparable with 8 wt% mono-phase Gtn-HPA. In addition, the compressive modulus of the 2 wt% dual-phase gel system incorporating the 8 wt% bead phase is nearly four-fold higher than the 2 wt% mono-phase gel (5.3 ± 0.4 kPa versus 1.5 ± 0.06 kPa). This novel injectable dual-phase Gtn-HPA composite thus combines the advantages of low-concentration Gtn-HPA (cell migration) with high-concentration Gtn-HPA (stiffness, degradation resistance, slower chemical release kinetics) to facilitate effective reparative/regenerative processes in musculoskeletal soft tissue.

Platelet-Derived Growth Factor Stimulated Migration of Bone Marrow Mesenchymal Stem Cells into an Injectable Gelatin-Hydroxyphenyl Propionic Acid Matrix.

Bone marrow mesenchymal stem cells (bMSCs) are responsible in the repair of injured tissue through differentiation into multiple cell types and secretion of paracrine factors, and thus have a broad application profile in tissue engineering/regenerative medicine, especially for the musculoskeletal system. The lesion due to injury or disease may be a closed irregular-shaped cavity deep within tissue necessitating an injectable biomaterial permissive of host (endogenous) cell migration, proliferation and differentiation. Gelatin-hydroxyphenyl propionic acid (Gtn-HPA) is a natural biopolymer hydrogel which is covalently cross-linked by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) in situ and can be delivered to the lesion by needle injection. Growth factors and cytokines can be directly incorporated into the gel or into nano- and micro-particles, which can be employed for sustained release of biomolecules while maintaining their bioactivity. In this study, we selected polyelectrolyte complex nanoparticles (PCNs) prepared with dextran sulfate and chitosan as the carrier for platelet-derived growth factor (PDGF)-BB and stromal cell-derived factor (SDF)-1α, which have been tested effectively in recruiting stem cells. Our in vitro results showed a high degree of viability of bMSCs through the process of Gtn-HPA covalent cross-linking gelation. The Gtn-HPA matrix was highly permissive of bMSC migration, proliferation, and differentiation. PDGF-BB (20 ng/mL) directly incorporated into the gel and, alternatively, released from PCNs stimulated bMSC migration and proliferation. There were only small differences in the results for the direct incorporation of PDGF into the gel compared with its release from PCNs, and for increased doses of the growth factor (200 ng/mL and 2 µg/mL). In contrast, SDF-1α elicited an increase in migration and proliferation only when released from PCNs; its effect on migration was notably less than PDGF-BB. The in vitro results demonstrate that PDGF-BB substantially increases migration of bMSCs into Gtn-HPA and their proliferation in the gel, and that these benefits can be derived from incorporation of a relatively low dose of the growth factor directly into the gel. These findings commend the use of Gtn-HPA/PDGF-BB as an injectable therapeutic agent to treat defects in musculoskeletal tissues.

A bioinspired gelatin-hyaluronic acid-based hybrid interpenetrating network for the enhancement of retinal ganglion cells replacement therapy.

Biomaterial-based cell replacement approaches to regenerative medicine are emerging as promising treatments for a wide array of profound clinical problems. Here we report an interpenetrating polymer network (IPN) composed of gelatin-hydroxyphenyl propionic acid and hyaluronic acid tyramine that is able to enhance intravitreal retinal cell therapy. By tuning our bioinspired hydrogel to mimic the vitreous chemical composition and mechanical characteristics we were able to improve in vitro and in vivo viability of human retinal ganglion cells (hRGC) incorporated into the IPN. In vivo vitreal injections of cell-bearing IPN in rats showed extensive attachment to the inner limiting membrane of the retina, improving with hydrogels stiffness. Engrafted hRGC displayed signs of regenerating processes along the optic nerve. Of note was the decrease in the immune cell response to hRGC delivered in the gel. The findings compel further translation of the gelatin-hyaluronic acid IPN for intravitreal cell therapy.

Controlling Growth Factor Diffusion by Modulating Water Content in Injectable Hydrogels.

Recent advancements in the delivery of therapeutics for retinal diseases include the development of injectable hydrogels, networks of one or more hydrophilic polymers that contain a high-volume fraction of water. These systems are of particular interest due to their biocompatibility, permeability to water-soluble metabolites, and function as minimally invasive injectable delivery vehicles. Recently, hydrogels for ophthalmic applications have been developed that display a controlled release of factors necessary for cellular survival and proliferation. Understanding the relationship between the volume water fraction and the physical, chemical, and diffusion properties of the hydrogel scaffold could aid in the improvement of existing drug delivery treatments for retinal regeneration. In this study, we compared the diffusion and release of human epidermal growth factor (hEGF) encapsulated in different injectable homogenous and heterogenous hydrogels, namely gelatin-hydroxyphenyl propionic acid (Gtn-HPA) and hyaluronic acid-tyramine (HA-Tyr)-based hydrogels. These experimental results were compared with the measured stiffness and water content of these hydrogels and applied to different diffusion theories of polymers to determine the model of best fit. We find that the normalized diffusion and release of hEGF increases with free water content in injectable hydrogels: ranging from 0.176 at 41% free water in HA-Tyr to 0.2 at 53% free water in Gtn-HPA, whereas it decreases with hydrogel stiffness: 600 Pa for Gtn-HPA and 1440 Pa for HA-Tyr. Further, we compared our experimental data with theoretical diffusion models. We found that homogeneous theoretical models, notably the hydrodynamic model (giving a normalized diffusion close to 0.2), provide the most suitable explanation for the measured solute diffusion coefficient. Impact statement Diffusion in a three-dimensional system is a key factor in designing new hydrogel-based materials. It allows to control and predict diffusion in implants and delivery systems. However, very little is done to explore and test the diffusion since it is a complex process. Many models can predict solute diffusion; however, practical application using these models has not yet been done. We have shown the variation of these models in a practical extent, which could have a tremendous impact on designing biomaterial for biological application as it allows one to understand the diffusion of injected drugs and growth factors.

Distribution of lubricin in the ruptured human rotator cuff and biceps tendon: a pilot study.

BACKGROUND: Lubricin is a lubricant for diarthrodial joint tissues and has antiadhesion properties; its presence in the (caprine) rotator cuff suggests it may have a role in intrafascicular lubrication. QUESTIONS/PURPOSES: To preliminarily address this role, we asked: (1) What is the distribution of lubricin in human ruptured supraspinatus and biceps tendons? (2) What are the potential cellular sources of lubricin? METHODS: We obtained seven torn rotator cuff samples and four torn biceps tendon samples from 10 patients; as control tissues, we obtained the right and left supraspinatus tendons from each of six cadavers. Specimens were fixed in formalin and processed for immunohistochemical evaluation using a monoclonal antibody for lubricin. RESULTS: We found lubricin as a discrete layer on the torn edges of all of the ruptured supraspinatus and biceps tendon samples. None of the transected edges of the tissues produced during excision of the tissues showed the presence of lubricin. Lubricin was found in 3% to 10% of the tendon cells in the cadaveric controls and in 1% to 29% of the tendon cells in the torn supraspinatus and biceps tendon samples. CLINICAL RELEVANCE: The lubricin layer on the torn edges of ruptured human supraspinatus and biceps tendons may interfere with the integrative bonding of the torn edges necessary for repair.