Choongsoo S. Shin

Current approaches to electrospun nanofibers for tissue engineering

The ultimate goal of tissue engineering is to replace damaged tissues by applying engineering technology and the principles of life sciences. To successfully engineer a desirable tissue, three main elements of cells, scaffolds and growth factors need to be harmonized. Biomaterial-based scaffolds serve as a critical platform both to support cell adhesion and to deliver growth factors. Various methods of fabricating scaffolds have been investigated. One recently developed method that is growing in popularity is called electrospinning. Electrospinning is known for its capacity to make fibrous and porous structures that are similar to natural extracellular matrix (ECM). Other advantages to electrospinning include its ability to create relatively large surface to volume ratios, its ability to control fiber size from micro- to nano-scales and its versatility in material choice. Although early work with electrospun fibers has shown promise in the regeneration of certain types of tissues, further modification of their chemical, biological and mechanical properties would permit future advancements. In this paper, current approaches to the development of modular electrospun fibers as scaffolds for tissue engineering are discussed. Their chemical and physical characteristics can be tuned for the regeneration of specific target tissues by co-spinning of multiple materials and by post-modification of the surface of electrospun fibers. In addition, topology or structure can also be controlled to elicit specific responses from cells and tissues. The selection of proper polymers, suitable surface modification techniques and the control of the dimension and arrangement of the fibrous structure of electrospun fibers can offer versatility and tissue specificity, and therefore provide a blueprint for specific tissue engineering applications.

The effect of isolated valgus moments on ACL strain during single-leg landing: A simulation study

Valgus moments on the knee joint during single-leg landing have been suggested as a risk factor for anterior cruciate ligament (ACL) injury. The purpose of this study was to test the influence of isolated valgus moment on ACL strain during single-leg landing. Physiologic levels of valgus moments from an in vivo study of single-leg landing were applied to a three-dimensional dynamic knee model, previously developed and tested for ACL strain measurement during simulated landing. The ACL strain, knee valgus angle, tibial rotation, and medial collateral ligament (MCL) strain were calculated and analyzed. The study shows that the peak ACL strain increased nonlinearly with increasing peak valgus moment. Subjects with naturally high valgus moments showed greater sensitivity for increased ACL strain with increased valgus moment, but ACL strain plateaus below reported ACL failure levels when the applied isolated valgus moment rises above the maximum values observed during normal cutting activities. In addition, the tibia was observed to rotate externally as the peak valgus moment increased due to bony and soft-tissue constraints. In conclusion, knee valgus moment increases peak ACL strain during single-leg landing. However, valgus moment alone may not be sufficient to induce an isolated ACL tear without concomitant damage to the MCL, because coupled tibial external rotation and increasing strain in the MCL prevent proportional increases in ACL strain at higher levels of valgus moment. Training that reduces the external valgus moment, however, can reduce the ACL strain and thus may help athletes reduce their overall ACL injury risk.

Valgus Plus Internal Rotation Moments Increase Anterior Cruciate Ligament Strain More Than Either Alone

PURPOSE To test the influence of combined knee valgus and internal tibial rotation moment on anterior cruciate ligament (ACL) strain during single-leg landing. We tested the following hypotheses: the combination of the valgus and internal rotation moments observed during single-leg landing produces a higher ACL strain than either moment applied individually, the combined rotational moments at the physiological levels observed could theoretically increase strain in the ACL high enough to rupture the ACL, and the location of the peak contact force was at the posterior-lateral side for combined loading. METHODS The study was conducted by applying in vivo human loading data to a validated simulation model of the three-dimensional dynamic knee joint to predict ACL strains. RESULTS The peak ACL strain increased nonlinearly when either applied valgus moment or internal rotation moment was increased in the model. When the two rotational moments were applied individually, neither caused ACL strain >0.077. However, when applied in combination, the two rotational moments had a much larger effect, and the predicted peak ACL strain increased up to 0.105. During landing, the peak contact force occurred at the posterior-lateral side of the tibial cartilage in the model when the combined maximum valgus moment and tibial internal rotation moments were applied. CONCLUSIONS Combined knee valgus and internal rotation moments increases ACL strain more than either alone. The combination of a valgus and internal rotational moment at magnitudes that occurs in vivo during landing can cause ACL strains that may be high enough to cause ACL rupture. This predicted high ACL strain and the contact force location suggest that combined valgus and internal tibial rotational moments during single-leg landing are relevant to ACL injuries.

Effective Immobilization of BMP-2 Mediated by Polydopamine Coating on Biodegradable Nanofibers for Enhanced in Vivo Bone Formation

Although bone morphogenic proteins (BMPs) have been widely used for bone regeneration, the ideal delivery system with optimized dose and minimized side effects is still active area of research. In this study, we developed bone morphogenetic protein-2(BMP-2) immobilized poly(l-lactide) (PLLA) nanofibers inspired by polydopamine, which could be ultimately used as membranes for guided bone regeneration, and investigated their effect on guidance of in vitro cell behavior and in vivo bone formation. Surface chemical analysis of the nanofibers confirmed successful immobilization of BMP-2 mediated by polydopamine, and about 90% of BMP-2 was stably retained on the nanofiber surface for at least 28 days. The alkaline phosphatase activity and calcium mineralization of human mesenchymal stem cells (hMSCs) after 14 days of in vitro culture was significantly enhanced on nanofibers immobilized with BMP-2. More importantly, BMP-2 at a relatively small dose was highly active following implantation to the critical-sized defect in the cranium of mice; radiographic analysis demonstrated that 77.8 ± 11.7% of newly formed bone was filled within the defect for a BMP-2-immobilized groups at the concentration of 124 ± 9 ng/cm(2), as compared to 5.9 ± 1.0 and 34.1 ± 5.5% recovery, for a defect-only and a polydopamine-only group, respectively. Scanning and transmission electron microscopy of samples from the BMP-2 immobilized group showed fibroblasts and osteoblasts with nanofiber strands in the middle of regenerated bone tissue, revealing the importance of interaction between implanted nanofibers and the neighboring extracellular environment. Taken together, our data support that the presentation of BMP-2 on the surface of nanofibers as immobilized by utilizing polydopamine chemistry may be an effective method to direct bone growth at relatively low local concentration.

Three-Dimensional In Vivo Patellofemoral Kinematics and Contact Area of Anterior Cruciate Ligament–Deficient and –Reconstructed Subjects Using Magnetic Resonance Imaging

PURPOSE The purpose of this study was to test whether (1) the 3-dimensional in vivo patellofemoral kinematics and patellofemoral contact area of anterior cruciate ligament (ACL)-deficient knees are different from those of normal, contralateral knees and (2) ACL reconstruction restores in vivo patellofemoral kinematics and contact area. METHODS Ten ACL-deficient knees and twelve ACL-reconstructed knees, as well as the contralateral uninjured knees, were tested. Magnetic resonance imaging was performed at full extension and 40 degrees of flexion under simulated partial weight-bearing conditions. Six-degrees of freedom patellofemoral kinematics, patellofemoral contact area, and contact location were analyzed by use of magnetic resonance image-based 3-dimensional patellofemoral knee models. RESULTS The patella in the ACL-deficient knees underwent significantly more lateral tilt during flexion (P < .05) and tended to translate more laterally (P = .083) than the patella in contralateral knees. After ACL reconstruction, no kinematic parameters were significantly different from those in contralateral knees. The patellofemoral contact areas of ACL-deficient knees at both the extended and flexed positions (37 +/- 22 mm(2) and 357 +/- 53 mm(2), respectively) were significantly smaller than those of contralateral knees (78 +/- 45 mm(2) and 437 +/- 119 mm(2), respectively) (P < .05). After reconstruction, the patellofemoral contact area of ACL-reconstructed knees in the extended position (86 +/- 41 mm(2)) was significantly larger (P < .05) than that of contralateral knees (50 +/- 34 mm(2)), but no difference was detected in the flexed position. Reproducibility of all patellofemoral kinematic parameters, contact centroid translation, and contact area showed coefficients of variation of less than 6.8%. CONCLUSIONS ACL injuries alter patellofemoral kinematics including patellar tilt and patellar lateral translation, but ACL reconstruction with hamstring or allograft restores altered patellar tilt. ACL injuries reduce the patellofemoral contact area at both the extended and flexed positions, but ACL reconstruction enlarges the patellofemoral contact area at extension and restores the normal contact area at low angles of flexion. LEVEL OF EVIDENCE Level III, case-control study.

In vivo tibiofemoral cartilage-to-cartilage contact area of females with medial osteoarthritis under acute loading using MRI

To investigate the effect of acute loading on in vivo tibiofemoral contact area changes in both compartments, and to determine whether in vivo tibiofemoral contact area differs between subjects with medial knee osteoarthritis (OA) and healthy controls.

Release Kinetics and in vitro Bioactivity of Basic Fibroblast Growth Factor: Effect of the Thickness of Fibrous Matrices

In this study, we fabricated non-woven matrices using blends of polycaprolactone and gelatin with various spinning volumes to control the immobilized heparin content, which was ultimately intended to increase the immobilization efficiency of bFGF. The amount of bFGF on the heparin conjugated fibrous matrices depended on the thicknesses of the swollen matrices ranging from 35.4 ± 6.5 to 162.3 ± 14.0 ng and ≈90% of the bFGF was gradually released over a period of up to 56 d. The released bFGF enhanced the proliferation of human umbilical vein endothelial cells and human mesenchymal stem cells. In conclusion, our heparin-conjugated fibrous matrices have the potential to be used as a growth factor delivery system in tissue engineering applications.

Influence of patellar ligament insertion angle on quadriceps usage during walking in anterior cruciate ligament reconstructed subjects

Reduced quadriceps contraction has been suggested as an adaptation to prevent anterior tibial translation in anterior cruciate ligament (ACL)‐deficient knees. This theory has been supported by a recent study that peak knee flexion moment (thought to be created by a decrease of quadriceps contraction) during walking was negatively correlated with patellar ligament insertion angle (PLIA) in ACL‐deficient knees, but not in contralateral, uninjured knees. In addition, the PLIA was significantly smaller in ACL‐deficient knees than in contralateral, uninjured knees. However, it is unknown whether ACL reconstruction restores the PLIA or whether the relationship between the PLIA and knee flexion moments previously observed in ACL‐deficient knees disappears. This study tested the following hypotheses: (1) The PLIA of ACL‐reconstructed knees is significantly smaller than the PLIA of uninjured contralateral knees; (2) Peak knee flexion moment (balanced by net quadriceps moment) during walking is negatively correlated with the PLIA in ACL‐reconstructed knees. The PLIA of 24 ACL‐reconstructed and contralateral knees were measured using MRI, and peak knee flexion moments during walking were measured. Results showed that the PLIA of ACL‐reconstructed (22.9 ± 4.4°) knees was not significantly smaller (p = 0.09, power = 0.99) than the PLIA of contralateral (24.1 ± 4.8°) knees. Peak knee flexion moment was not correlated with the PLIA following ACL reconstruction (R2 = 0.016, power = 0.99). However, the magnitude of the knee flexion moment remained significantly lower in ACL‐reconstructed knees. In summary, this study has shown that the PLIA of ACL‐reconstructed knees returned to normal and that patients no longer adapt their gait in response to the PLIA, though quadriceps function did not return to normal levels.

Gender differences of sagittal knee and ankle biomechanics during stair-to-ground descent transition.

BACKGROUND Falls on stairs often result in severe injury and occur twice as frequently in women. However, gender differences in kinetics and kinematics during stair descent are unknown. Thus, this study aimed to determine whether gender differences of knee and ankle biomechanics exist in the sagittal plane during the stair-to-ground descending transition. It was hypothesized that 1) women would reveal higher ground-toe-trochanter angle and lower ground-toe length during stair-to-ground descent transition than men; and 2) women would reveal lower peak knee extension moment during stair-to-ground descent transition than men. METHODS Fifteen men and fifteen women were recruited and performed a stair descent activity. Kinetic and kinematic data were obtained using a force plate and motion capture system. FINDINGS The women performed the stair descent with a lower peak knee extension moment and a peak knee power at the early weight acceptance phase. The women also revealed a higher ground-toe-trochanter angle and a lower ground-toe length, which indicated a more forward position of the lower extremity relative to the toe contact point at both the initial contact and at the time of peak kinematic and kinetic events. INTERPRETATION This study found that knee and ankle kinematics and kinetics differed significantly between the genders due to differences in ground-toe-trochanter angle. Women have a different stair descending strategy that reduces the demand of the lower extremity muscle function, but this strategy seems to increase the risk of falls.

The Effect of Backpack Load Carriage on the Kinetics and Kinematics of Ankle and Knee Joints During Uphill Walking

The purpose of this study was to investigate the effect of load carriage on the kinematics and kinetics of the ankle and knee joints during uphill walking, including joint work, range of motion (ROM), and stance time. Fourteen males walked at a self-selected speed on an uphill (15°) slope wearing military boots and carrying a rifle in hand without a backpack (control condition) and with a backpack. The results showed that the stance time significantly decreased with backpack carriage (p < .05). The mediolateral impulse significantly increased with backpack carriage (p < .05). In the ankle joints, the inversion-eversion, and dorsi-plantar flexion ROM in the ankle joints increased with backpack carriage (p < .05). The greater dorsi-plantar flexion ROM with backpack carriage suggested 1 strategy for obtaining high plantar flexor power during uphill walking. The result of the increased mediolateral impulse and inversion-eversion ROM in the ankle joints indicated an increase in body instability caused by an elevated center of mass with backpack carriage during uphill walking. The decreased stance time indicated that an increase in walking speed could be a compensatory mechanism for reducing the instability of the body during uphill walking while carrying a heavy backpack.