The Effects of Autologous Fat Transfer in an In Vitro Model of Basal Joint Osteoarthritis.

PURPOSE: Basal joint osteoarthritis (OA) is a highly prevalent and debilitating condition. Recent clinical evidence suggests that autologous fat transfer (AFT) may be a promising, minimally invasive treatment for this condition. However, the mechanism of action is not fully understood. It is theorized that AFT reduces inflammation in the joint, functions to regenerate cartilage, or acts as a mechanical buffer. The purpose of this study was to better understand the underlying mechanism of AFT using an in vitro model. We hypothesize that the addition of stromal vascular fraction (SVF) cells will cause a reduction in markers of inflammation. METHODS: Articular chondrocytes were expanded in culture. Liposuction samples were collected from human subjects and processed similarly to AFT protocols to isolate SVF rich in adipose-derived stem cells. A control group was treated with standard growth media, and a positive control group (OA group) was treated with inflammatory cytokines. To mimic AFT, experimental groups received inflammatory cytokines and either a low or high dose of SVF. Expression of relevant genes was measured, including interleukin (IL)-1ß, IL-1 receptor antagonist, and matrix metalloproteinases (MMP). RESULTS: Compared to the OA group, significant decreases in IL-1ß, MMP3, and MMP13 expression on treatment day 3 were found in the high-dose SVF group, while MMP13 expression was also significantly decreased in the low-dose SVF group on day 3. CONCLUSIONS: In this study, we found that SVF treatment reduced expression of IL-1ß, MMP3, and MMP13 in an in vitro model of OA. These results suggest that an anti-inflammatory mechanism may be responsible for the clinical effects seen with AFT in the treatment of basal joint OA. CLINICAL RELEVANCE: An anti-inflammatory mechanism may be responsible for the clinical benefits seen with AFT for basal joint arthritis.

An Ex Vivo Model of Posterior Tracheomalacia With Evaluation of Potential Treatment Modalities.

OBJECTIVE: Posterior tracheomalacia (TM) is characterized by excessive intraluminal displacement of the tracheal membranous wall. Recently, novel surgical strategies for repair of posterior TM have been introduced. To our knowledge, these strategies have not been evaluated in a model of posterior TM. Thus, we sought to design an ex vivo mechanical model of posterior TM to evaluate potential repair interventions. METHODS: A model for posterior TM was created with partial thickness longitudinal incisions to the posterior aspect of ex vivo porcine trachea. Three groups of tracheas were tested: (1) control (unmanipulated), (2) posterior TM (injury), and (3) intervention (repair). Interventions included external splinting with 0.3 and 0.5 mm bioresorbable plates, posterior tracheopexy, and injection tracheoplasty with calcium hydroxylapatite. An airtight tracheal system was created to measure tracheal wall collapse with changes in negative pressure. A bronchoscope and pressure transducer were connected to either end. Cross-sectional area of the tracheal lumen was analyzed using ImageJ software (National Institutes of Health, Bethesda, MD). RESULTS: Average percent reduction in cross-sectional area of the tracheal lumen was compared using a two-tailed paired t-test. Significant differences were found between control and TM groups (p < 0.019). There was no significant difference between control and external splinting and posterior tracheopexy groups (p > 0.14). CONCLUSION: We describe an ex vivo model for posterior TM that replicates airway collapse. External splinting and tracheopexy interventions showed recovery of the injured tracheal segment. Injection tracheoplasty did not improve the TM. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:2000-2006, 2023.

A two-stage in vivo approach for implanting a 3D printed tissue-engineered tracheal replacement graft: A proof of concept.

OBJECTIVES: To optimize a 3D printed tissue-engineered tracheal construct using a combined in vitro and a two-stage in vivo technique. METHODS: A 3D-CAD (Computer-aided Design) template was created; rabbit chondrocytes were harvested and cultured. A Makerbot Replicator™ 2x was used to print a polycaprolactone (PCL) scaffold which was then combined with a bio-ink and the previously harvested chondrocytes. In vitro: Cell viability was performed by live/dead assay using Calcein A/Ethidium. Gene expression was performed using quantitative real-time PCR for the following genes: Collagen Type I and type II, Sox-9, and Aggrecan. In vivo: Surgical implantation occurred in two stages: 1) Index procedure: construct was implanted within a pocket in the strap muscles for 21 days and, 2) Final surgery: construct with vascularized pedicle was rotated into a segmental tracheal defect for 3 or 6 weeks. Following euthanasia, the construct and native trachea were explanted and evaluated. RESULTS: In vitro: After 14 days in culture the constructs showed >80% viable cells. Collagen type II and sox-9 were overexpressed in the construct from day 2 and by day 14 all genes were overexpressed when compared to chondrocytes in monolayer. IN VIVO: By day 21 (immediately before the rotation), cartilage formation could be seen surrounding all the constructs. Mature cartilage was observed in the grafts after 6 or 9 weeks in vivo. CONCLUSION: This two-stage approach for implanting a 3D printed tissue-engineered tracheal replacement construct has been optimized to yield a high-quality, printable segment with cellular growth and viability both in vitro and in vivo.

Effect of Combined Leukocyte-Poor Platelet-Rich Plasma and Hyaluronic Acid on Bone Marrow-Derived Mesenchymal Stem Cell and Chondrocyte Metabolism.

OBJECTIVE: Given the potential applications of combined biologics, the authors sought to evaluate the in vitro effect of combined platelet-rich plasma (PRP) and hyaluronic acid (HA) on cellular metabolism. DESIGN: Bone marrow-derived mesenchymal stem cells (BMSCs) and chondrocytes were obtained from the femurs of Sprague-Dawley rats. An inflammatory model was created by adding 10 ng/mL interleukin-1-beta to culture media. Non-crosslinked high-molecular-weight HA, activated-PRP (aPRP), and unactivated-PRP (uPRP) were tested. Cellular proliferation and gene expression were measured at 1 week. Genes of interest included aggrecan, matrix metalloproteinase (MMP)-9, and MMP-13. RESULTS: Combined uPRP-HA was associated with a significant increase in chondrocyte and BMSC proliferation at numerous preparations. There was a trend of increased chondrocyte aggrecan expression with combined PRP-HA. The greatest and only significant decrease in BMSC MMP-9 expression was observed with combined PRP-HA. While a significant reduction of BMSC MMP-13 expression was seen with PRP and HA-alone, a greater reduction was observed with PRP-HA. MMP-9 chondrocyte expression was significantly reduced in cells treated with PRP-HA. PRP-alone and HA-alone at identical concentrations did not result in a significant reduction. The greatest reduction of MMP-13 chondrocyte expression was observed in chondrocytes plus combined PRP-HA. CONCLUSIONS: We demonstrated a statistically significant increase in BMSC and chondrocyte proliferation and decreased expression of catabolic enzymes with combined PRP-HA. These results demonstrate the additive in vitro effect of combined PRP-HA to stimulate cellular growth, restore components of the articular extracellular matrix, and reduce inflammation.

Oral Administration of a Chemically Modified Curcumin, TRB-N0224, Reduced Inflammatory Cytokines and Cartilage Erosion in a Rabbit ACL Transection Injury Model.

OBJECTIVE: To evaluate the effects of TRB-N0224, a chemically modified curcumin (CMC) with zinc binding properties and improved pharmacokinetics, in a rabbit anterior cruciate ligament (ACL) transection injury-induced model of osteoarthritis (OA). DESIGN: Thirty-eight skeletally mature New Zealand white rabbits were studied in 4 groups: a sham with arthrotomy (n = 6), control with ACL transection (n = 6), and 2 treatment groups with ACL transection and administration of TRB-N0224 at low (25 mg/kg/day) (n = 13) and high (50 mg/kg/day) (n = 13) doses. After euthanization at 12 weeks, outcomes were measured by post-necropsy gross morphology, biomechanics, and cartilage and synovium histology. Rabbit blood ELISA quantified cytokine and matrix metalloproteinase (MMP) concentrations at 0, 4, 8, and 12 weeks. RESULTS: Both treatment doses had fewer distal femoral condyle erosive defects than the control; the low dose demonstrated a mean 78% decrease (P < 0.01). Histologically, the low- and high-dose treatment groups had fewer cartilage pathologic changes and less severe synovitis than the control. CMC alone did not have a major effect on the biomechanics of healthy cartilage or cartilage in the ACL transection model, as demonstrated in 5 of the 6 measured properties/regions (P < 0.05). ELISA results suggested that the key mediators of OA, (interleukin) IL-1ß, IL-6, TNFα (tumor necrosis factor-α), MMP-9, and MMP-13, had decreased concentrations with TRB-N0224 treatment at different time points between weeks 4 to 12 (P < 0.05). CONCLUSIONS: In the pathogenesis of OA, an imbalance exists between catabolic and anabolic mediators. These results suggest the potential of TRB-N0224 to modulate MMP and cytokine levels, slowing the macroscopic and histopathological progression of OA.

Three-Dimensional Bioprinting in Orthopaedics.

Three-dimensional (3D)-printing technology has evolved dramatically in the last 30 years, from large machines with poor resolution to those with micron-level capabilities that sit on a desktop. This technology is being utilized in numerous medical applications, particularly in orthopaedic surgery. Over the past decade, technological advances have allowed for the application of this technology to the field of tissue engineering through the process of 3D bioprinting. Of interest to orthopaedic surgeons, active areas of research utilizing this technology involve the bioprinting of articular cartilage, bone, menisci, and intervertebral discs.

5-Aminolevulinic acid tumor paint and photodynamic therapy for myxofibrosarcoma: an in vitro study.

BACKGROUND: 5-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft tissue sarcomas is not well documented. Myxofibrosarcoma, a subtype of soft tissue sarcoma with a high local recurrence rate, may benefit from similar types of treatment. The purpose of this study was to analyze the effects of 5-ALA tumor paint and PDT on a myxofibrosarcoma cell line. METHODS: Tumor paint was assessed by exposing micromass pellets of human adipose-derived stromal (ADS) cells or myxofibrosarcoma (MUG-Myx1) cells to 5-ALA. Cell pellets were then visualized using a microscope at established excitation and emission wavelengths. Corrected total cell fluorescence was calculated per accepted protocols. Photodynamic therapy was similarly assessed by exposing ADS and MUG-Myx1 cells to 5-ALA, with subsequent analysis via flow cytometry and real-time confocal microscopy. RESULTS: The use of 5-ALA tumor paint led to a selective fluorescence in MUG-Myx1 cells. Findings were confirmed by flow cytometry. Interestingly, flow cytometry results showed progressive selective cell death with increasing 5-ALA exposure as a result of the PDT effect. PDT was further confirmed using confocal microscopy, which revealed progressive cellular bubble formation consistent with advancing stages of cell death-a finding that was not seen in control ADS cells. CONCLUSIONS: 5-ALA tumor paint and PDT were successfully used on a human myxofibrosarcoma cell line (MUG-Myx1). Results from this study showed both selective fluorescent tagging and selective cytotoxicity of 5-ALA toward malignant myxofibrosarcoma cells, while sparing benign adipose control cells. This finding was further confirmed in a dramatic time-lapse video, visually confirming active, targeted cell death. 5-ALA's two-pronged application of selective tumor identification and cytotoxicity may transform surgical and medical approaches for treating soft tissue sarcomas.

Culture Conditions that Support Expansion and Chondrogenesis of Middle-Aged Rat Mesenchymal Stem Cells.

OBJECTIVE: Rats are an early preclinical model for cartilage tissue engineering, and a practical species for investigating the effects of aging. However, rats may be a poor aging model for mesenchymal stem cells (MSCs) based on laboratory reports of a severe decline in chondrogenesis beyond young adulthood. Such testing has not been conducted with MSCs seeded in a scaffold, which can improve the propensity of MSCs to undergo chondrogenesis. Therefore, the objective of this study was to evaluate chondrogenesis of middle-aged rat MSCs encapsulated in agarose. DESIGN: MSCs from 14- to 15-month-old rats were expanded, seeded into agarose, and cultured in chondrogenic medium with or without 5% serum for 15 days. Samples were evaluated for cell viability and cartilaginous extracellular matrix (ECM) accumulation. Experiments were repeated using MSCs from 6-week-old rats. RESULTS: During expansion, middle-aged rat MSCs demonstrated a diminishing proliferation rate that was improved ~2-fold in part by transient exposure to chondrogenic medium. In agarose culture in defined medium, middle-aged rat MSCs accumulated ECM to a much greater extent than negative controls. Serum supplementation improved cell survival ~2-fold, and increased ECM accumulation ~3-fold. Histological analysis indicated that defined medium supported chondrogenesis in a subset of cells, while serum-supplementation increased the frequency of chondrogenic cells. In contrast, young rat MSCs experienced robust chondrogenesis in defined medium that was not improved with serum-supplementation. CONCLUSIONS: These data demonstrate a previously-unreported propensity of middle-aged rat MSCs to undergo chondrogenesis, and the potential of serum to enhance chondrogenesis of aging MSCs.

3D-bioprinted tracheal reconstruction: an overview.

Congenital tracheomalacia and tracheal stenosis are commonly seen in premature infants. In adulthood, are typically related with chronic obstructive pulmonary disease, and can occur secondarily from tracheostomy, prolong intubation, trauma, infection and tumors. Both conditions are life-threatening when not managed properly. There are still some surgical limitations for certain pathologies, however tissue engineering is a promising approach to treat massive airway dysfunctions. 3D-bioprinting have contributed to current preclinical and clinical efforts in airway reconstruction. Several strategies have been used to overcome the difficulty of airway reconstruction such as scaffold materials, construct designs, cellular types, biologic components, hydrogels and animal models used in tracheal reconstruction. Nevertheless, additional long-term in vivo studies need to be performed to assess the efficacy and safety of tissue-engineered tracheal grafts in terms of mechanical properties, behavior and, the possibility of further stenosis development.

A 3-dimensional bioprinted tracheal segment implant pilot study: Rabbit tracheal resection with graft implantation.

OBJECTIVES: Surgical reconstruction of tracheal disease has expanded to include bioengineering and three dimensional (3D) printing. This pilot study investigates the viability of introducing a living functional tracheal replacement graft in a rabbit animal model. METHODS: Seven New Zealand White rabbits were enrolled and six completed participation (one intraoperative mortality). Tracheal replacement grafts were created by impregnating 3D printed biodegradable polycaprolactone (PCL) tracheal scaffolds with rabbit tracheal hyaline chondrocytes. 2 cm of native trachea was resected and the tracheal replacement graft implanted. Subjects were divided into two equal groups (n = 3) that differed in their time of harvest following implantation (three or six weeks). Tracheal specimens were analyzed with intraluminal telescopic visualization and histopathology. RESULTS: The two groups did not significantly differ in histopathology or intraluminal diameter. All sections wherein the implant telescoped over native trachea (anastomotic ends) contained adequate hyaline cartilage formation (i.e. chondrocytes within lacuna, surrounding extracellular matrix, and strong Safranin O staining). Furthermore, the PCL scaffold was surrounded by a thin layer of fibrous tissue. All areas without membranous coverage contained inadequate or immature cartilage formation with inflammation. The average intraluminal stenosis was 83.4% (range 34.2-95%). CONCLUSIONS: We report normal cartilage growth in a tracheal replacement graft when chondrocytes are separated from the tracheal lumen by an intervening membrane. When no such membrane exists there is a propensity for inflammation and stenosis. These findings are important for future construction and implantation of tracheal replacement grafts. LEVEL OF EVIDENCE: Not applicable: this is an in vivo animal trial.

Cadaveric Study of the Safety and Device Functionality of Magnetically Controlled Growing Rods After Exposure to Magnetic Resonance Imaging.

STUDY DESIGN: Cadaveric study. OBJECTIVE: To establish the safety and efficacy of magnetically controlled growing rods (MCGRs) after magnetic resonance imaging (MRI) exposure. SUMMARY OF BACKGROUND DATA: MCGRs are new and promising devices for the treatment of early-onset scoliosis (EOS). A significant percentage of EOS patients have concurrent spinal abnormalities that need to be monitored with MRI. There are major concerns of the MRI compatibility of MCGRs because of the reliance of the lengthening mechanism on strongly ferromagnetic actuators. METHODS: Six fresh-frozen adult cadaveric torsos were used. After thawing, MRI was performed four times each: baseline, after implantation of T2-T3 thoracic rib hooks and L5-S1 pedicle screws, and twice after MCGR implantation. Dual MCGRs were implanted in varying configurations and connected at each end with cross connectors, creating a closed circuit to maximize MRI-induced heating. Temperature measurements and tissue biopsies were obtained to evaluate thermal injury. MCGRs were tested for changes to structural integrity and functionality. MRI images obtained before and after MCGR implantation were evaluated. RESULTS: Average temperatures increased incrementally by 1.1°C, 1.3°C, and 0.5°C after each subsequent scan, consistent with control site temperature increases of 1.1°C, 0.8°C, and 0.4°C. Greatest cumulative temperature change of +3.6°C was observed adjacent to the right-sided actuator, which is below the 6°C threshold cited in literature for clinically detectable thermal injury. Histologic analysis revealed no signs of heat-induced injury. All MCGR actuators continued to function properly according to the manufacturer's specifications and maintained structural integrity. Significant imaging artifacts were observed, with the greatest amount when dual MCGRs were implanted in standard/offset configuration. CONCLUSIONS: We demonstrate minimal MRI-induced temperature change, no observable thermal tissue injury, preservation of MCGR-lengthening functionality, and no structural damage to MCGRs after multiple MRI scans. Expectedly, the ferromagnetic actuators produced substantial MR imaging artifacts. LEVEL OF EVIDENCE: Level V.

Optimization of Degradation Profile for New Scaffold in Cartilage Repair.

Objective To establish whether a novel biomaterial scaffold with tunable degradation profile will aid in cartilage repair of chondral defects versus microfracture alone in vitro and in a rat model in vivo. Design In vitro-Short- and long-term degradation scaffolds were seeded with culture expanded articular chondrocytes or bone marrow mesenchymal stem cells. Cell growth and differentiation were evaluated with cell morphological studies and gene expression studies. In vivo-A microfracture rat model was used in this study to evaluate the repair of cartilage and subchondral bone with the contralateral knee serving as the empty control. The treatment groups include (1) empty osteochondral defect, (2) polycaprolactone copolymer-based polyester polyurethane-urea (PSPU-U) caffold short-term degradative profile, and (3) PSPU-U scaffold long-term degradative profile. After placement of the scaffold, the rats were then allowed unrestricted activity as tolerated, and histological analyses were performed at 4, 8, and 16 weeks. The cartilage defect was measured and compared with the contralateral control side. Results In vitro-Long-term scaffolds showed statistically significant higher levels of aggrecan and type II collagen expression compared with short-term scaffolds. In vivo-Within 16 weeks postimplantation, there was new subchondral bone formation in both scaffolds. Short-term scaffolds had a statistically significant increase in defect filling and better qualitative histologic fill compared to control. Conclusions The PSPU short-term degradation scaffold may aid in cartilage repair by ultimately incorporating the scaffold into the microfracture procedure.

Ex vivo tracheomalacia model with 3D-printed external tracheal splint.

OBJECTIVE: To design and evaluate an ex vivo model of tracheomalacia with and without a three-dimensional (3D)-printed external tracheal splint. STUDY DESIGN: Prospective, ex vivo animal trial. METHODS: Three groups of ex vivo porcine tracheas were used: 1) control (unmanipulated trachea), 2) tracheomalacia (tracheal rings partially incised and crushed), and 3) splinted tracheomalacia (external custom tracheal splint fitted onto group 2 trachea). Each end of an ex vivo trachea was sealed with a custom-designed and 3D-printed cap; a transducer was placed through one end to measure the pressure inside the trachea. Although the negative pressure was applied to the tracheal lumen, the tracheal wall collapse was measured externally and internally using a bronchoscope. Each group had at least three recorded trials. Tracheal diameter was evaluated using ImageJ software (National Institutes of Health, Bethesda, MD) and was averaged between two raters. RESULTS: Average tracheal occlusion percentage was compared using Student t test. The average occlusion was 31% for group 1, 87.4% for group 2, and 20% for group 3. Significant differences were found between the control and tracheomalacia groups (P < 0.01) and the tracheomalacia and splinted tracheomalacia groups (P < 0.01). There was no significant difference between the control and splinted tracheomalacia groups (P = 0.13). Applied pressure was plotted against occlusion and regression line slope differed between the tracheomalacia (0.91) and control (0.12) or splinted tracheomalacia (0.39) groups. CONCLUSION: We demonstrate the potential for an ex vivo tracheomalacia model to reproduce airway collapse and show that this collapse can be treated successfully with a 3D-printed external splint. These results are promising and justify further studies. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:950-955, 2017.

Sonographic evaluation of knee cartilage defects implanted with preconditioned scaffolds.

OBJECTIVES: The purpose of this study was to develop a novel method for creating an acellular bioactive scaffold, to prove its efficacy in vivo and in vitro for the augmentation of biological repair, and to confirm that sonographic microscopy is a viable modality for monitoring the healing process of osteochondral defects implanted with preconditioned bioactive scaffolds. METHODS: Rabbit marrow stromal cells were retrovirally transduced with either bone morphogenetic protein 7 (BMP-7) or insulinlike growth factor 1 (IGF-1) genes, cultured for 9 weeks in nonwoven poly-L-lactic acid scaffolds, and then frozen and lyophilized. The knees were evaluated at 3, 6, and 12 weeks after surgery using 20-MHz ultrasound and then prepared for routine histologic analysis. B-scans of the extracellular matrix defects were compared to histologic results. RESULTS: Control defects showed a void or a mixture of fibrocartilage tissue. Both types of scaffolds resulted in a higher percentage (both P< .001) of primarily hyaline cartilage tissue with intact articular surfaces. The osteochondral defects were clearly observed in each sonographic signature. There were no differences between images of scaffolds treated with IGF-1 or BMP-7. Extracellular matrix regrowth was found to closely parallel (R(2) = 0.968; P < .003) the histologic images. A 3-mm defect depth and a 2.5-mm scaffold thickness were measured on the sonograms, comparing well to actual dimensions. CONCLUSIONS: There was a gradual increase in healing bordering the defects for the 3-, 6-, and 12-week samples. Also, we have shown that sonography can aid in monitoring implantation of preconditioned scaffolds in osteochondral defects and thus assessing the healing process and cartilage/bone quality.

Tendon repair augmented with a novel circulating stem cell population.

Tendon ruptures are common sports-related injuries that are often treated surgically by the use of sutures followed by immobilization. However, tendon repair by standard technique is associated with long healing time and often suboptimal repair. Methods to enhance tendon repair time as well as the quality of repair are currently unmet clinical needs. Our hypothesis is that the introduction of a unique stem cell population at the site of tendon transection would result in an improved rate and quality of repair. Achilles tendons of fifty-one Sprague-Dawley rats were transected and suture-repaired. In half of the rats, a biodegradable scaffold seeded with allogenic circulating stem cells was placed as an onlay to the defect site in addition to the suture repair. The other half was treated with suture alone to serve as the control group. Animals were randomized to a two-, four-, or six-week time group. At the time of necropsy, tendons were harvested and prepared for either biomechanical or histological analysis. Histological slides were evaluated in a blinded fashion with the use of a grading scale. By two weeks, the experimental group demonstrated a significant improvement in repair compared to controls with no failures. Average histological scores of 0.6 and 2.6 were observed for the experimental and control group respectively. The experimental group demonstrated complete bridging of the transection site with parallel collagen fiber arrangement. By four weeks, both groups showed a continuing trend of healing, with the scaffold group exceeding the histological quality of the tissue repaired with suture alone. Biomechanically, the experimental group had a decreasing cross-sectional area with time which was also associated with a significant increase in the ultimate tensile strength of the tendons, reaching 4.2MPa by six weeks. The experimental group also achieved a significantly higher elastic toughness by six weeks and saw an increase in the tensile modulus, reaching 31Mpa by six weeks. The use of circulating stem cells as an adjunct in tendon repair demonstrates superior biomechanical properties and an improved level of histological organization, when compared to the suture alone control group. These improvements were not previously observed when gene therapy, protein therapy, or current tissue engineering technologies were used.

Tendon phenotype should dictate tissue engineering modality in tendon repair: a review.

Advancements in the technical aspects of tendon repair have significantly improved the treatment of tendon injuries. Arthroscopic techniques, suture material, and improved rehabilitation have all been contributing factors. Biological augmentation and tissue engineering appear to have the potential to improve clinical outcomes as well. After review of the physiology of tendon repair, three critical components of tissue engineering can be discerned: the cellular component, the carrier vehicle (matrix or scaffold), and the bioactive component (growth factors, platelet rich plasma). These three components are discussed with regard to each of three tendon types: Intra-synovial (flexor tendon), extra-synovial (Achilles tendon), and extra-synovial tendon under compression (rotator cuff). Scaffolds, biologically enhanced scaffolds, growth factors, platelet rich plasma, gene therapy, mesenchymal stem cells, and local environment factors in combination or alone may contribute to tendon healing. In the future it may be beneficial to differentiate these modes of healing augmentation with regard to tendon subtype.

Histologic stages of healing correlate with restoration of tensile strength in a model of experimental tendon repair.

Much current research is focused on biologic enhancement of the tendon repair process. To evaluate the different methods, which include a variety of gene therapy and tissue engineering techniques, histological and biomechanical testing is often employed. Both modalities offer information on the progress and quality of repair; however, they have been historically considered as two separate entities. Histological evaluation is a less costly undertaking; however, there is no validated scoring scale to compare the results of different studies or even the results within a given study. Biomechanical testing can provide validated outcome measures; however, it is associated with increased cost and is more labor intensive. We hypothesized that a properly developed, objective histological scoring system would provide a validated outcome measure to compare histological results and correlate with biomechanics. In an Achilles tendon model, we have developed a histological scoring scale to assess tendon repair. The system grades collagen orientation, angiogenesis, and cartilage induction. In this study, histology scores were plotted against biomechanical testing results of healing tendons which indicated that a strong linear correlation exists between the histological properties of repaired tendons and their biomechanical characteristics. Concordantly, this study provides a pragmatic and financially feasible means of evaluating repair while accounting for both the histology and biomechanical properties observed in surgically repaired, healing tendon.

New methods to diagnose and treat cartilage degeneration.

Lesions in articular cartilage can result in significant musculoskeletal morbidity and display unique biomechanical characteristics that make repair difficult, at best. Several surgical procedures have been devised in an attempt to relieve pain, restore function, and delay or stop the progression of cartilaginous lesions. Advanced MRI and ultrasonography protocols are currently used in the evaluation of tissue repair and to improve diagnostic capability. Other nonoperative modalities, such as injection of intra-articular hyaluronic acid or supplementary oral glucosamine and chondroitin sulfate, have shown potential efficacy as anti-inflammatory and symptom-modifying agents. The emerging field of tissue engineering, involving the use of a biocompatible, structurally and mechanically stable scaffold, has shown promising early results in cartilage tissue repair. Scaffolds incorporating specific cell sources and bioactive molecules have been the focus in this new exciting field. Further work is required to better understand the behavior of chondrocytes and the variables that influence their ability to heal articular lesions. The future of cartilage repair will probably involve a combination of treatments in an attempt to achieve a regenerative tissue that is both biomechanically stable and, ideally, identical to the surrounding native tissues.