The Skeletal Oncology Research Group Machine Learning Algorithm (SORG-MLA) for predicting prolonged postoperative opioid prescription after total knee arthroplasty: an international validation study using 3,495 patients from a Taiwanese cohort.

BACKGROUND: Preoperative prediction of prolonged postoperative opioid use (PPOU) after total knee arthroplasty (TKA) could identify high-risk patients for increased surveillance. The Skeletal Oncology Research Group machine learning algorithm (SORG-MLA) has been tested internally while lacking external support to assess its generalizability. The aims of this study were to externally validate this algorithm in an Asian cohort and to identify other potential independent factors for PPOU. METHODS: In a tertiary center in Taiwan, 3,495 patients receiving TKA from 2010-2018 were included. Baseline characteristics were compared between the external validation cohort and the original developmental cohorts. Discrimination (area under receiver operating characteristic curve [AUROC] and precision-recall curve [AUPRC]), calibration, overall performance (Brier score), and decision curve analysis (DCA) were applied to assess the model performance. A multivariable logistic regression was used to evaluate other potential prognostic factors. RESULTS: There were notable differences in baseline characteristics between the validation and the development cohort. Despite these variations, the SORG-MLA ( https://sorg-apps.shinyapps.io/tjaopioid/ ) remained its good discriminatory ability (AUROC, 0.75; AUPRC, 0.34) and good overall performance (Brier score, 0.029; null model Brier score, 0.032). The algorithm could bring clinical benefit in DCA while somewhat overestimating the probability of prolonged opioid use. Preoperative acetaminophen use was an independent factor to predict PPOU (odds ratio, 2.05). CONCLUSIONS: The SORG-MLA retained its discriminatory ability and good overall performance despite the different pharmaceutical regulations. The algorithm could be used to identify high-risk patients and tailor personalized prevention policy.

Diagnostic accuracy of algorithms to define incident and second hip fractures: A Taiwan validation study.

BACKGROUND: Previous epidemiological researchers have used various algorithms to identify a second hip fracture; however, there has been no validation of these algorithms to date. This study aimed to verify existing algorithms for identifying second hip fracture under the International Classification of Diseases diagnostic coding systems. Furthermore, we examined the validity of two newly proposed algorithms that integrated the concept of periprosthetic fractures and laterality of the ICD-10 coding system. METHODS: Claims data of patients hospitalized for hip fracture from National Taiwan University Hospitals between 2007 and 2020 were retrieved. Hip fracture was confirmed by 2 orthopaedic surgeons with medical records and imaging data as gold standards. The validity of 9 existing and 2 newly proposed algorithms for identifying second hip fracture was evaluated. RESULTS: The positive predictive value (PPV) range between 84% and 90% in existing algorithms for identifying second hip fractures. Noteworthy, the longer time interval for discrimination resulted in slightly increased PPV (from 87% to 90%), while decreased sensitivity noticeably (from 87% to 72%). When considering the information about periprosthetic fracture, the PPV increased to 91% without diminished sensitivity. The PPV of the newly proposed ICD-10-specific algorithm was 100%. CONCLUSION: Algorithms integrated clinical insights of periprosthetic fractures and laterality concept of ICD-10 coding system provided satisfactory validity and help precisely define second hip fracture in future database research.

A simple method to improve the antibiotic elution profiles from polymethylmethacrylate bone cement spacers by using rapid absorbable sutures.

OBJECTIVE: Antibiotic-loaded bone cement beads and spacers have been widely used for orthopaedic infection. Poor antibiotic elution is not capable of eradicating microbial pathogens and could lead to treatment failure. The elution profiles differ among different cement formulations. Although Simplex P cement has the least release amount, it is widely used due to its ready availability. Previous methods aiming to improve the elution profiles were not translated well to clinical practice. We sought to address this by using easily available materials to improve the elution profile of antibiotics from PMMA, which allows clinicians to implement the method intraoperatively. METHODS: Vancomycin was mixed with Simplex P cement. We used Vicryl Rapide sutures to fabricate sustained-release cement beads by repetitively passing the sutures through the beads and/or mixing suture segments into the cement formulation. Vancomycin elution was measured for 49 days. The mechanism of antibiotic release was observed with gross appearance and scanning electron microscopic images. The antimicrobial activities against MRSA were tested using an agar disk diffusion bioassay. RESULTS: Passing Vicryl Rapide sutures through cement beads significantly improved the elution profiles in the 7-week period. The increased ratios were 9.0% on the first day and 118.0% from the 2nd day to the 49th day. Addition of suture segments did not increase release amount. The Vicryl Rapide sutures completely degraded at the periphery and partially degraded at the center. The antibiotic particles were released around the suture, while antibiotic particles kept densely entrapped in the control group. The antimicrobial activities were stronger in passing suture groups. CONCLUSION: Passing fast absorbable sutures through PMMA cement is a feasible method to fabricate sustained-release antibiotic bone cement. Intra-cement tunnels can be formed, and the effect can last for at least 7 weeks. It is suitable for a temporary spacer between two stages of a revision surgery.

The five year outcome of a clinical feasibility study using a biphasic construct with minced autologous cartilage to repair osteochondral defects in the knee.

PURPOSE: Autologous minced cartilage has been used to repair cartilage defects. We have developed a biphasic cylindrical osteochondral construct for such use in human knees, and report the five year post-operative outcomes. METHODS: Ten patients with symptomatic osteochondral lesion at femoral condyles were treated by replacing pathological tissue with the osteochondral composites, each consisted a DL-poly-lactide-co-glycolide chondral phase and a DL-poly-lactide-co-glycolide/ß-tricalcium phosphate osseous phase. A flat chamber between the two phases served as a reservoir to house double-minced (mechanical pulverization and enzymatical dissociation) autologous cartilage graft. The osteochondral lesion was drill-fashioned a pit of identical dimensions as the construct. Graft-laden construct was press fit to the pit. Post-operative outcome was evaluated using Knee Injury and Osteoarthritis Outcome Score (KOOS) up to five years. Regenerated tissue was sampled with arthroscopic needle biopsy for histology at one year, and imaged with magnetic resonance at one, three, and five years to evaluate the neocartilage with MOCART chart. Subchondral bone integration was evaluated with computed tomography at three and five years. RESULTS: Nine patients completed the five-year follow-up. Post-operative mean KOOS, except that of the "symptom" subscale, had been significantly higher than pre-operation from one year and maintained to five years. The change of MOCRAT scores of the regenerated cartilage paralleled the change of KOOS. The osseous phase remained mineralized during the five-year period, yet did not fully integrate with the host bone. CONCLUSIONS: This novel construct for chondrocyte implantation yielded promising mid-term outcome. It repaired the osteochondral lesion with hyaline-like cartilage durable for at least five years.

Acute and Long-Term Effects of Mechanotherapy on the Outcome After an Achilles Repair: A Prospective Cohort Study With Historical Controls.

OBJECTIVES: To evaluate the effects of vibration on Achilles' tendon microcirculation and characteristics following surgical repair of Achilles' tendon rupture. DESIGN: Cohort study with historical controls. SETTING: A university institute. PARTICIPANTS: Participants (N=32), including 19 (16 men, 3 women; median [range] age: 43.0 [25.0-57.0] years) and 13 (10 men, 3 women; 44.00 [29.0-60.0] years) in the vibration (application to the ball of the foot, 30Hz, 2mm amplitude, 4kg pressure, and self-administration) and control groups, respectively, who underwent unilateral Achilles' tendon repairs were recruited. INTERVENTION: A 4-week vibration intervention in the vibration group. MAIN OUTCOME MEASUREMENTS: The tendon microcirculation was measured after the first session of vibration. The participants were evaluated repeatedly with bilateral follow-up measurements of tendon stiffness, 3 functional outcome tests, and a questionnaire survey. RESULTS: Acute effects of the vibration were observed immediately after the 5-minute vibration (P≤.001). Lower total hemoglobin and oxygen saturation were respectively observed (P=.043) in the repaired legs 3 and 6 months postsurgery in the vibration group as compared with the control group. The vibration group also showed greater tendon stiffness, heel raising height and hopping distance 3 or 6 months postoperation in both the repaired and noninjured legs (all P<.05). The microcirculatory characteristics 2 months postoperation were correlated with the outcomes at 6 months postoperation. CONCLUSIONS: Differences in microcirculatory characteristics and better rehabilitation outcomes were observed in the legs with an Achilles repair that underwent the early vibration intervention.

Topical anesthesia for staple removal from surgical wounds on the knee: a prospective, double-blind, randomized trial.

BACKGROUND: Staple removal from surgical wounds is painful. Only a few articles have provided expert opinions using anesthetic cream for such a problem; however, direct application of the anesthetic cream to a wound may cause infection. A safe alternative can be an anesthetic patch without wound contact. MATERIALS AND METHODS: This was a prospective, double-blind, randomized clinical trial. Sixty patients who underwent primary total knee replacement were assigned to an experimental group or control group. One lidocaine patch was applied around the surgical wound for each patient in the experimental group. Alternatively, the adhesive sides of the lidocaine patches were shielded with waterproof films in the control group. A resident peeled off the patch before a single nursing practitioner removed the staples. Pain was assessed with the 10-cm visual analog scale, and a face pain scale-revised was performed. The patients and the nursing practitioner were blind to the management. RESULTS: Mean visual analog scale and face pain scale-revised scores were significantly lower in the experimental group. The mean pain score was significantly lower in the experimental group if the application time was >47 min; for patients with application time of 47 min or shorter, the score was comparable with the mean pain scores of the control group (P = 0.215). CONCLUSIONS: Removal of the metal skin staples after total knee arthroplasty is associated with moderate-to-severe pain. The lidocaine patch applied topically around the surgical wound could effectively reduce the pain during the procedure, without remarkable complications such as systemic adverse effects or wound contamination.

Early neuromechanical outcomes of the triceps surae muscle-tendon after an Achilles' tendon repair.

OBJECTIVES: To compare the neuromechanical and functional characteristics of the legs of athletes who underwent unilateral Achilles' tendon repair and their controls, and to determine any correlation between the characteristics. DESIGN: A case-control and cross-sectional study. SETTING: A university institute. PARTICIPANTS: Male athletes (N=33) were recruited; 23 in the ≥3- and <12-month postsurgical group (median age, 29.8y; age range, 21.9-40.0y) and 10 in the control group (median age, 30.0y; age range, 21.1-39.5y) who had not undergone any surgery. INTERVENTION: Surgical Achilles' tendon repair in the study group. MAIN OUTCOME MEASURES: Bilateral measurements of activation strategy involving the triceps surae and tibialis anterior muscles, mechanical properties of the Achilles' tendon, and explosive performance tests were conducted. RESULTS: Compared with the noninjured legs and the control legs, the repaired legs showed lower normalized rates of electromyographic rise (RER) in the soleus, gastrocnemius medialis, and gastrocnemius lateralis (P ranged between .006 and .001); and less tendon stiffness, greater hysteresis, and less rates of force development (RFD) (P ranged between .006 and <.001). Repaired legs had less ankle dorsiflexion, a shorter 1-leg hopping distance, and lower balance scores (P≤.001). The noninjured legs of the athletes who underwent surgical Achilles' tendon repair had a lower normalized RER (0-50 ms) in the soleus and lateral gastrocnemius when compared with the legs of the healthy controls (P=.011). The neuromechanical outcomes and explosive performances showed correlations with RFD, 1-leg hopping distance, and balance score. CONCLUSIONS: The athletes who underwent unilateral Achilles' tendon repair demonstrated bilateral neuromechanical deficits within the 1-year postsurgical period.

Comparison of quadriceps-sparing minimally invasive and medial parapatellar total knee arthroplasty: a 2-year follow-up study.

BACKGROUND/PURPOSE: Quadriceps-sparing minimally invasive total knee arthroplasty (TKA) has been proposed to limit surgical dissection without compromising surgical outcome. We conducted a prospective and randomized study to compare the outcomes of patients who underwent quadriceps-sparing TKA with the outcomes of those who underwent standard medial parapatellar TKA, after a 2-year follow-up period. METHODS: Eighty primary TKA procedures that were to be performed in 60 osteoarthritis patients were randomly assigned to either a quadriceps-sparing (40 knees) or a standard medial parapatellar (40 knees) group. All surgeries were designed to set the prosthesis with a femoral component alignment of 7° valgus and a tibial component alignment that was perpendicular to the tibial shaft. Surgical time and tourniquet time were recorded. Outcome variables included knee function, as defined by a hospital for special surgery knee score; quadriceps muscle strength, which was measured by an isokinetic dynamometer; pain, as indicated on a visual analog scale; prosthetic position, which was measured on plain radiograph; and range of motion. RESULTS: Patients who underwent the 38 quadriceps-sparing and 37 standard TKA procedures completed the 2-year follow-up period without any infection or revision. The mean surgical time and tourniquet time were significantly longer in the quadriceps-sparing group. The mean peak quadriceps muscle strength, hamstring muscle strength, normalized muscle balance (hamstring/quadriceps ratio), pain score, function score, and range of motion were comparable in both groups at 2 months and 2 years. In the quadriceps-sparing group, both the femoral and the tibial components were significantly more varus-deviated from the expected position. CONCLUSIONS: Patients undergoing quadriceps-sparing and standard medial parapatellar TKA had comparable outcomes for quadriceps muscle strength, hamstring-quadriceps balance, and knee function; however, the quadriceps-sparing TKA was more time consuming surgically and resulted in a less accurate prosthesis position.

Prospective Application of Partially Digested Autologous Chondrocyte for Meniscus Tissue Engineering.

BACKGROUND: Meniscus tissue engineering has yet to achieve clinical application because it requires chondrogenic induction and in vitro cell expansion. Contrarily, cartilage engineering from autologous chondrocytes has been successfully applied in one-stage surgery. If the natural chondrogenic potential of meniscus cells can be demonstrated, meniscus tissue engineering would have more value in clinical settings. MATERIALS AND METHODS: In total, 10 menisci and pieces of cartilage were obtained during total knee replacements. The tissues were collected for cell isolation and expansion. Their chondrogenic properties were examined by immunohistofluorescence and gene expression analyses. RESULTS: In native cartilage, immunofluorescence demonstrated the presence of collagen I, aggrecan, and traces of collagen I, whereas comparable staining was seen in the inner and middle meniscus. The presence of collagen I but the absence of collagen II and aggrecan were observed in the outer meniscus. In passage 2, chondrocytes showed the presence of collagen II and aggrecan, and the absence of vimentin. The vimentin and aggrecan staining were comparable in the inner and middle meniscus cells, whereas the outer cells showed only vimentin staining. In the gene expression analyses, the expressions of collagen II and aggrecan in the native chondrocyte and the inner and middle meniscus were higher than those of the cells from the outer meniscus, but they were not different in collagen I. In the passage 2 culture, chondrocytes had a higher expression of collagen II and aggrecan than the meniscus cells. Cells from the inner and middle areas had higher collagen II and aggrecan expression than those from the outer meniscus. CONCLUSION: Without chondrogenic induction, inner and middle meniscus cells possess a chondrogenic phenotype. Specifically, native meniscus cells exhibited more robust chondrogenic potential compared with those of the passage 2 monolayer culture.

A machine learning algorithm for predicting prolonged postoperative opioid prescription after lumbar disc herniation surgery. An external validation study using 1,316 patients from a Taiwanese cohort.

BACKGROUND CONTEXT: Preoperative prediction of prolonged postoperative opioid prescription helps identify patients for increased surveillance after surgery. The SORG machine learning model has been developed and successfully tested using 5,413 patients from the United States (US) to predict the risk of prolonged opioid prescription after surgery for lumbar disc herniation. However, external validation is an often-overlooked element in the process of incorporating prediction models in current clinical practice. This cannot be stressed enough in prediction models where medicolegal and cultural differences may play a major role. PURPOSE: The authors aimed to investigate the generalizability of the US citizens prediction model SORG to a Taiwanese patient cohort. STUDY DESIGN: Retrospective study at a large academic medical center in Taiwan. PATIENT SAMPLE: Of 1,316 patients who were 20 years or older undergoing initial operative management for lumbar disc herniation between 2010 and 2018. OUTCOME MEASURES: The primary outcome of interest was prolonged opioid prescription defined as continuing opioid prescription to at least 90 to 180 days after the first surgery for lumbar disc herniation at our institution. METHODS: Baseline characteristics were compared between the external validation cohort and the original developmental cohorts. Discrimination (area under the receiver operating characteristic curve and the area under the precision-recall curve), calibration, overall performance (Brier score), and decision curve analysis were used to assess the performance of the SORG ML algorithm in the validation cohort. This study had no funding source or conflict of interests. RESULTS: Overall, 1,316 patients were identified with sustained postoperative opioid prescription in 41 (3.1%) patients. The validation cohort differed from the development cohort on several variables including 93% of Taiwanese patients receiving NSAIDS preoperatively compared with 22% of US citizens patients, while 30% of Taiwanese patients received opioids versus 25% in the US. Despite these differences, the SORG prediction model retained good discrimination (area under the receiver operating characteristic curve of 0.76 and the area under the precision-recall curve of 0.33) and good overall performance (Brier score of 0.028 compared with null model Brier score of 0.030) while somewhat overestimating the chance of prolonged opioid use (calibration slope of 1.07 and calibration intercept of -0.87). Decision-curve analysis showed the SORG model was suitable for clinical use. CONCLUSIONS: Despite differences at baseline and a very strict opioid policy, the SORG algorithm for prolonged opioid use after surgery for lumbar disc herniation has good discriminative abilities and good overall performance in a Han Chinese patient group in Taiwan. This freely available digital application can be used to identify high-risk patients and tailor prevention policies for these patients that may mitigate the long-term adverse consequence of opioid dependence: https://sorg-apps.shinyapps.io/lumbardiscopioid/.

Collagenase treatment of cartilaginous matrix promotes fusion of adjacent cartilage.

In articular cartilage-repair, grafts usually fuse unsatisfactorily with surrounding host cartilage. Enzymatic dissociation of cartilaginous matrix to free chondrocytes may benefit fusion. We tested such a hypothesis with human cartilage in vitro, and with porcine cartilage in vivo. Human articular cartilage was collected from knee surgeries, cut into disc-and-ring sets, and randomly distributed into three groups: disc-and-ring sets in Group 1 were left untreated; in Group 2 only discs, and in Group 3 both discs and rings were treated with enzyme. Each disc-and-ring reassembly was cultured in a perfusion system for 14 days; expression of cartilage marker proteins and genes was evaluated by immunohistochemistry and PCR. Porcine articular cartilage from knees was similarly fashioned into disc-and-ring combinations. Specimens were randomly distributed into a control group without further treatment, and an experimental group with both disc and ring treated with enzyme. Each disc-and-ring reassembly was transplanted into subcutaneous space of a nude mouse for 30 days, and retrieved to examine disc-ring interface. In in vitro study with human cartilage, a visible gap remained at disc-ring interfaces in Group 1, yet became indiscernible in Group 2 and 3. Marker genes, including type II collagen, aggrecan and Sox 9, were well expressed by chondrocytes in all specimens, indicating that chondrocytes' phenotype retained regardless of enzymatic treatment. Similar results were found inin vivo study with porcine cartilage. Enzymatic dissociation of cartilaginous matrix promotes fusion of adjacent cartilage. The clinical relevance may be a novel method to facilitate integration of repaired cartilage in joints.

Sulfation pattern of chondroitin sulfate in human osteoarthritis cartilages reveals a lower level of chondroitin-4-sulfate.

Chondroitin sulfates (CS) account for more than 80% of the glycosaminoglycans of articular cartilage, which impart its physiological functions. We quantified the absolute concentration of the CS components of the full thickness cartilages from the knees of patients with terminal-phase osteoarthritis. Osteochondrol biopsies were removed from the medial femoral condyle and lateral femoral condyle of sixty female patients received total knee arthroplasty, aged from 58 to 83 years old. We found the total CS concentrations and chondroitin-4-sulfate disaccharide were significantly lowered in osteoarthritic samples. Microstructure analysis indicated while chondroitin-0-sulfate was equally distributed across different zones of the osteoarthritic cartilages, chondroitin-4-sulfate is significantly less in the deep zones. Down-regulation of sulfotransferases, the enzymes responsible for CS sulfation, in the lesion site of cartilage were observed. Our study suggested chondroitin-4-sulfate down-regulation can be a diagnostic marker for degraded osteoarthritis cartilage, with potential implications in cartilage regeneration.

Repair of articular cartilage defects: review and perspectives.

Articular cartilage defects heal poorly and lead to catastrophic degenerative arthritis. Clinical experience has indicated that no existing medication substantially promotes the healing process and the cartilage defect requires surgical replacement, preferably with an autograft. However, there is a shortage of articular cartilage that can be donated for autografting. A review of previous unsuccessful experiences reveals the reason for the current strategy to graft cartilage defects with regenerated cartilage. Autologous cartilage regeneration is a cell-based therapy in which autogenous chondrocytes or other chondrogenic cells are cultured to constitute cartilaginous tissue according to the principles of tissue engineering. Current studies are concentrating on improving such techniques from the three elements of tissue engineering, namely the cells, biomaterial scaffolds, and culture conditions. Some models of articular cartilage regeneration have yielded good repair of cartilage defects, in animal models and clinical settings, but the overall results suggest that there is room for improvement of this technique before its routine clinical application. Autologous cartilage regeneration remains the mainstay for repairing articular cartilage defects but more studies are required to optimize the efficacy of regeneration. A more abundant supply of more stable cells, i.e. capable of maintaining the phenotype of chondrogenesis, has to be identified. Porous scaffolds of biocompatible, biodegradable materials that maintain and support the presentation of the chondrogenic cells need to be fabricated. If the cells are not implanted early to allow their in vivo constitution of cartilage, a suitable in vitro cultivation method has to be devised for a consistent yield of regenerative cartilage.

Muscular Morphomechanical Characteristics After an Achilles Repair.

BACKGROUND: The purpose of the study was to compare the morphomechanical and functional characteristics during maximal isometric, concentric, and eccentric contractions in the legs of patients that underwent unilateral Achilles tendon repair with those in their noninjured control legs. METHODS: Twenty participants (median age = 38.2 years; range, 21.1-57.3 years) who underwent Achilles repair between 3 and 12 months ago were recruited with the following measures: (1) mechanical stiffness of the aponeurosis and (2) electromyography and medial gastrocnemius fascicle angle and length, standing muscle and tendon length, and height of heel rise with isometric contraction. RESULTS: Compared to the noninjured legs, the repaired legs showed less resting fascicle length, standing muscle length, isometric plantarflexion torque, and heel raise distance ( Ps ranged between .044 and <.001). During the concentric and eccentric phases of the raising and lowering test, the repaired legs demonstrated less fascicle length ( P ≤ .028) but greater tendinous tissue length ( Ps ranged between .084 and <.001) and fascicle angle ( Ps ranged between .247 and .008) and fewer change magnitudes of the fascicle length and tendinous tissue length ( P ≤ .003). The change magnitudes of the morphological characteristics showed correlations with the torque or distance. CONCLUSION: Selecting the appropriate surgical repair and rehabilitation for Achilles tendon ruptures is recommended for restoring the length and mechanical strength of the muscle-tendon unit of plantar-flexion muscles. LEVEL OF EVIDENCE: Level III, comparative study.

Repair of porcine articular cartilage defect with a biphasic osteochondral composite.

Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with beta-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone.

Injecting partially digested cartilage fragments into a biphasic scaffold to generate osteochondral composites in a nude mice model.

This study proposed a novel scaffold with heterogeneous morphology that mimics the natural tissue. Its upper part contains a hollow cavity surrounded by a wall of poly(L-lactic-co-glycolic acid) (PLGA) porous membrane for injecting cartilage tissue and cells. An interconnecting porous structure located under the hollow cavity was made of composite materials that combined PLGA and beta-tricalcium phosphate (beta-TCP) to simulate the subchondral bone. Adult pig articular cartilage was cut and sieved into small fragments. The tissue fragments was partially digested by 0.1% collagenase for 0, 2, 4, and 6 h and injected into the hollow cavity of the biphasic scaffold. The biphasic scaffolds were then implanted into the subcutaneous pocket of nude mice for 4 weeks. No tissue bonding or new cartilaginous tissue formation was identified in the cartilage fragment without enzymatic treatment. The cartilage fragments digested with 2 h of collagenase digestion were partially integrated after implantation. The integrative properties of the cartilage fragment depended on the extent of enzymatic digestion. Releasing cells at the tissue surface enhanced confluence and bonding of the cartilage fragment matrix. Complete integration of the cartilage fragments and cartilage remodeling were achieved by digestion of the tissue fragments with 4 h of enzymatic treatment. The neocartilage grew from the upper hollow cavity into the lower PLGA/beta-TCP porous structure, forming an interface similar to that formed between cartilage and subchondral bone. This study combined the osteochondral scaffold and limited cartilage tissues to generate cartilage tissue in vivo intending for repairing full-thickness articular cartilage defects.

Microcontact printing of laminin on oxygen plasma activated substrates for the alignment and growth of Schwann cells.

Microenvironment mimicking biological situation is a vital issue in tissue regeneration. With much progress being made, one of the major challenges remains to develop a convenient method to fabricate the scaffold microenvironment suitable for cell attachment and proliferation. This article demonstrates the efficacy of microcontact printed laminin, an extracellular matrix protein, on three different oxygen plasma treatment substrates-tissue culture polystyrene, poly(methyl methacrylate) films, and chitosan films-for alignment and growth of the Schwann cells in in vitro culturing. Replica molding of polydimethylsiloxane elastomeric stamps, fabricated from patterned SU-8 structure on silicon master, was used to print laminin on the three substrates. Pattern and growth of Schwann cells for low (10(3) cells/cm(2)) and increased cell density (2 x 10(4) cells/cm(2)) on the varied substrates with and without microcontact printed laminin were characterized. Results of in vitro cell culture of Schwann cells showed a high degree of cell orientation on the laminin-micropatterned substrates for both cell densities. However, different cell seeding densities will strongly impact the morphology and orientation of Schwann cells. Microcontact printing proves to be a convenient means to pattern cell-recognition molecules on scaffold for cell-guilded growth in tissue regeneration.

Characteristics of Intratendinous Microcirculation Shortly After an Achilles Rupture and Subsequent Treatment Outcomes.

BACKGROUND: Early microcirculatory responses after experimental tenotomy are critical to the healing of tendons and their ultimate tensile strength. The effects of changes in microcirculation on the outcomes of tendon healing, however, have not been determined. OBJECTIVES: To assess microcirculation values in injured Achilles tendons in the first 3 months after surgical repair and to correlate the inter-limb microcirculatory changes with functional outcomes at 3 and 6 months after surgery. DESIGN: Case-control study. SETTING: A university sports physiotherapy laboratory. PARTICIPANTS: Thirteen subjects (median age: 45 years; range: 34.8-51.9 years) with a repaired Achilles tendon were recruited. METHODS OR INTERVENTION: Surgical repair. MAIN OUTCOME MEASUREMENTS: Measurements were obtained at 1, 2, 3, and 6 months after surgery. Bilateral measurements of tendon microcirculation (total hemoglobin [THb] and oxygen saturation [StO2]) were recorded at the first 3 time points, whereas outcome measures of a Taiwan Chinese version of the Victorian Institute of Sport Assessment Scale-Achilles questionnaire, one-leg hopping distance, the star excursion balance test, and the heel raise index were conducted at the third and fourth time points. Correlations between the inter-limb microcirculatory changes, eg, between the measurements at 2 months and 1 month (2-1) after surgery, at 3 months and 2 months (3-2) after surgery, and at 3 months and 1 month (3-1) after surgery, and the outcome measures were investigated. RESULTS: Compared with the noninjured tendons, the repaired Achilles demonstrated greater THb (at 1, 2, and 3 months; P = .017, .008, and .012 respectively) and StO2 (at 3 months; P = .017). Furthermore, the THb2-1 and THb3-2, StO2 2-1, and StO2 3-2 showed correlations with the heel raise index, differences in the star excursion balance test and one-leg hopping distance between the noninjured leg and injured leg, and Taiwan Chinese version of the Victorian Institute of Sport Assessment Scale-Achilles questionnaire scores (rho -0.921 to 0.855). CONCLUSIONS: Changes in the inter-limb microcirculation shortly after Achilles repair were correlated with subsequent symptoms and functional symmetry. LEVEL OF EVIDENCE: III.