Hu-ping Hsu - Academia.edu (original) (raw)

Papers by Hu-ping Hsu

PubMed, Sep 1, 1989

Clinical experience has shown that deformation of patella components can lead to loosening or exc... more Clinical experience has shown that deformation of patella components can lead to loosening or excessive particulate debris, requiring revision. Factors affecting patella performance are the degree of congruity, the shear forces occurring due to tracking variations, and the excessive patellofemoral forces, particularly at higher flexion angles. A method was devised to load the patella with a constant force against the femoral component. The load was applied through a range of flexion. The deformation and wear patterns resembled those of retrieved clinical specimens. All-plastic components suffered from local deformation and underlying bone failure, whereas metal backing led to eventual penetration of the metal onto the femoral flange. Increased conformity of the patella component onto the femoral flange improved the situation for all-plastic and metal-backed designs by increasing the contact area and the available thickness of plastic.

Journal of Arthroplasty, 1987

One thousand sixty-nine consecutive cemented Kinematic Condylar total knee arthroplasties perform... more One thousand sixty-nine consecutive cemented Kinematic Condylar total knee arthroplasties performed by one group of orthopaedists were studied. The maximum follow-up period was 7 years. Most patients had rheumatoid arthritis or osteoarthritis, and the average patient age was 67 years (range, 12-90 years). Aseptic revisions for loosening were required for only one tibial component and six patella components. Average postoperative flexion was 2.5-107 degrees. The preoperative to postoperative change in range of flexion was not affected by the tilt angle of the tibial component in the sagittal plane. With the use of external alignment guides, the average postoperative alignment was ideal but the standard deviation was high; the standard deviation and the extremes were lower when intramedullary guides were used. There was a 14% incidence of femoral radiolucency and a 30% incidence of tibial radiolucency, which increased only slightly with time. Most radiolucencies on the tibial side were small and restricted to the extreme edges; rarely did radiolucency occur around the central peg. More than one half of the thicker radiolucencies occurred adjacent to wedge-shaped bone defects that were filled with cement.

The Journal of Bone & Joint Surgery, 1997

Articular cartilage has a limited capacity for repair. In recent clinical and animal experiments,... more Articular cartilage has a limited capacity for repair. In recent clinical and animal experiments, investigators have attempted to elicit the repair of defects of articular cartilage by injecting cultured autologous chondrocytes under a periosteal flap (a layer of periosteum). The objective of the present study was to determine the effect of cultured autologous chondrocytes on healing in an adult canine model with use of histomorphometric methods to assess the degree of repair. A total of forty-four four-millimeter-diameter circular defects were created down to the zone of calcified cartilage in the articular cartilage of the trochlear groove of the distal part of the femur in fourteen dogs. The morphology and characteristics of the original defects were defined in an additional six freshly created defects in three other dogs. Some residual noncalcified articular cartilage, occupying approximately 2 per cent of the total cross-sectional area of the defect, was sometimes left in the defect. The procedure sometimes damaged the calcified cartilage, resulting in occasional microfractures or larger fractures, thinning of the zone of calcified cartilage, or, rarely, small localized penetrations into subchondral bone. The forty-four defects were divided into three treatment groups. In one group, cultured autologous chondrocytes were implanted under a periosteal flap. In the second group, the defect was covered with a periosteal flap but no autologous chondrocytes were implanted. In the third group (the control group), the defects were left empty. The defects were analyzed after twelve or eighteen months of healing. Histomorphometric measurements were made of the percentage of the total area of the defect that became filled with repair tissue, the types of tissue that filled the defect, and the integration of the repair tissue with the adjacent cartilage at the sides of the defects and with the calcified cartilage at the base of the defect. In histological sections made through the center of the defects in the three groups, the area of the defect that filled with new repair tissue ranged from a mean total value of 36 to 76 per cent, with 10 to 23 per cent of the total area consisting of hyaline cartilage. Integration of the repair tissue with the adjacent cartilage at the edges of the defect ranged from 16 to 32 per cent in the three groups. Bonding between the repair tissue and the calcified cartilage at the base of the defect ranged from 41 to 89 per cent. With the numbers available, we could detect no significant difference among the three groups with regard to any of the parameters used to assess the quality of the repair. In the two groups in which a periosteal flap was sutured to the articular cartilage surrounding the defect, the articular cartilage showed degenerative changes that appeared to be related to that suturing.

Journal of Orthopaedic Research, 2019

with the execution of the surgical procedures, tissue processing, evaluation and interpretation o... more with the execution of the surgical procedures, tissue processing, evaluation and interpretation of the data, histopathological assessments, and writing of the original draft. M.S. was part of the conceptualization and research design of the study, methodology, evaluation and interpretation of the data, writing of the revision draft, study coordination, administration, supervision of maintaining the integrity of the study, and fund acquisition. M.R.N. was part of the writing of the original draft and revision draft, manuscript preparation and submission, and editorial revisions management. J.W.S. was part of the This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

The Journal of Bone and Joint Surgery

ABSTRACT

Orthopedic Clinics of North America

Revision rates, complication rates, and the bone-cement interface reaction of 1,069 condylar tota... more Revision rates, complication rates, and the bone-cement interface reaction of 1,069 condylar total knee replacements were reviewed to help decide if conventional total knee replacement continues to be appropriate for the older low-demand patient. This knee replacement series was also compared with two published series of total hip replacements from the same institution. The conclusions are (1) in medium-term follow-up, total knee replacement is as good as or superior to total hip replacement and (2) based on bone-cement interface analysis, survival of total knee replacement is expected to be superior to conventional total hip replacement ten years postoperatively.

Clinical Orthopaedics and Related Research

The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro a... more The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro activity of the cells associated with the loosening process in seven dogs. The cells were isolated and maintained in culture for sufficient periods of time so that their biologic activity could be studied as well as the effect of different agents added to the cells in vivo or in vitro. The biologic response as determined by interleukin-1 and prostaglandin E2 activity paralleled the roentgenographic appearance of loosening and the technetium images and observations made at the time of revision surgery. The correlation between clinical, roentgenographic, histologic, and biochemical loosening indicates that the canine model is suitable for investigating the mechanisms of prosthetic failure. A canine model permits the study of possible nonsurgical therapeutic interventions with the ultimate hope of stopping or slowing the loosening process.

Clinical Orthopaedics and Related Research

The defect made to the level of the tidemark in a canine model has been used in several prior inv... more The defect made to the level of the tidemark in a canine model has been used in several prior investigations of various articular cartilage repair procedures. Direct comparison of the repair method, 15 weeks postoperatively, showed a significant correlation between the degree to which the calcified cartilage layer and subchondral bone were disrupted and the amount of tissue filling. Moreover, when it forms, hyaline cartilage most frequently occurs superficial to intact calcified cartilage. Many of the chondrocytic cells and fibroblasts expressed the gene for a contractile muscle actin, alpha-smooth muscle actin. However, the role of this actin isoform is yet in question. These findings may inform future strategies for cartilage repair.

Restorative neurology and neuroscience, 2001

The purpose of this study was to characterize the effects of implantation of a collagen tube on h... more The purpose of this study was to characterize the effects of implantation of a collagen tube on healing and scar formation following transection of tbc adult rat spinal cord. The spinal cords of adult rats were completely transected at the mid-thoracic level. At 30 days after injury, the cellular and extra-cellular components of repair tissue present within tubulated and non-tubulated (control) wounds were compared using qualitative and quantitative histological techniques. The presence of the tube reduced fibrocollagenous scar invasion into the gap, promoted astrocyte migration, and oriented axonal and connective tissue components of the repair tissue. Tube implants supported the regeneration of a substantial number of myelinated axons. A notable finding was the identification of cells containing a contractile actin isoform in the healing spinal cord. The tubulation model allows for the study of spinal cord wound healing and axon elongation in a controlled experimental environment ...

Wound Repair and Regeneration, 2000

The objective of this study was to evaluate the types of tissue resulting from spontaneous healin... more The objective of this study was to evaluate the types of tissue resulting from spontaneous healing of surgically created defects in adult canine articular cartilage up to 29 weeks postoperatively, with specific attention directed toward the presence and distribution of cells containing the contractile actin isoform, alpha-smooth muscle actin. Two 4-mm diameter defects were made in the trochlear groove to the depth of the tidemark in 20 adult mongrel dogs. The areal percentage of specific tissue types in the reparative material was determined histomorphometrically. Immunohistochemistry was employed to evaluate the percentage of alpha-smooth muscle actin-containing cells. The results showed that approximately 50% of the chondrocytes in the superficial zone of the uninvolved articular cartilage expressed alpha-smooth muscle actin. A significantly lower percentage of alpha-smooth muscle actin-positive chondrocytes appeared in the uninvolved deep zone. Notably, the deep zone adjacent to the defect contained a greater percentage of such cells than in the uninvolved deep zone. Also of interest was that a greater percentage of nonvascular cells in the hyaline cartilage and fibrocartilage of the reparative tissue contained alpha-smooth muscle actin-positive cells, compared to the fibrous tissue in the defects. The findings of this study revealed that canine articular cartilage has some potential for spontaneous regeneration, including integration with the calcified cartilage zone. By 29 weeks, up to 40% of an areal cross section of an untreated full-thickness chondral defect was found to fill with hyaline cartilage, with up to 19% judged histologically similar to articular cartilage. The results warrant further consideration of the role of alpha-smooth muscle actin in chondrocytes in normal articular cartilage and in reparative tissue.

Tissue Engineering Part A, 2013

The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineer... more The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration.

Tissue Engineering Part A, 2012

A multifaceted therapeutic approach involving biomaterial scaffolds, neurotrophic factors, exogen... more A multifaceted therapeutic approach involving biomaterial scaffolds, neurotrophic factors, exogenous cells, and antagonists to axon growth inhibitors may ultimately prove necessary for the treatment of defects resulting from spinal cord injury (SCI). The objective of this study was to begin to lay the groundwork for such strategies by implanting type I collagen scaffolds alone and incorporating individually a soluble Nogo receptor, chondroitinase ABC (ChABC), and mesenchymal stem cells (MSCs) into a standardized 3-mm-long hemiresection defect in the rat spinal cord. Statistically significant improvement in hindlimb motor function between the first and fourth weeks post-SCI was recorded for the scaffold-alone group and for the ChABC and MSC groups, but not the control group. Four weeks post-SCI, the scaffolds appeared intact with open pores, which were infiltrated with host cells. Of note is that in some cases, a few growth-associated protein 43 (GAP-43)-positive axons were seen reaching the center of the scaffold in the scaffold-alone and ChABC groups, but not in control animals. Angiogenic cells were prevalent in the scaffolds; however, the number of both macrophages and angiogenic cells in the scaffolds was significantly less than in the control lesion at 4 weeks. The results lay the foundation for future dose-response studies and to further investigate a range of therapeutic agents to enhance the regenerative response in SCI.

Tissue Engineering, 1998

... and Women's Hospital, Harvard Medical School, Boston, Massachusetts; presented at th... more ... and Women's Hospital, Harvard Medical School, Boston, Massachusetts; presented at the inaugural meeting of the Tissue Engineering Soci-ety, Orlando, Florida, December ... 22. Ohlsen, L., and Widenfalk, B. The early development of articular cartilage after perichondrial grafting ...

Tissue Engineering, 2001

Lapine and canine marrow stromal cells were found to contain a contractile actin isoform, alpha-s... more Lapine and canine marrow stromal cells were found to contain a contractile actin isoform, alpha-smooth muscle actin (SMA), by immunohistochemistry and Western blot analysis. The SMA was found to be incorporated into stress fibers that were prominently displayed by the cells in monolayer culture. The cell content of this actin isoform increased with passage number. The contractility of SMA-expressing stromal cells was demonstrated by their contraction of collagen-glycosaminoglycan analogs of extracellular matrix into which they were seeded. The demonstration that marrow-derived stromal cells express the SMA gene may explain recent findings of this expression in musculoskeletal connective tissue cells including osteoblasts, chondrocytes, and fibrochondrocytes that may be derived from this mesenchymal stem cell. The implications of these findings for tissue engineering strategies employing marrow stromal cells are also discussed.

Tissue Engineering, 1997

ABSTRACT In previous studies, we have examined the substrate preferences of peripheral nervous sy... more ABSTRACT In previous studies, we have examined the substrate preferences of peripheral nervous system (PNS) axons elongating within a 15-mm gap in the rat sciatic nerve. Gaps were bridged with tubes filled with one of several porous collagen-glycosaminoglycan (GAG) copolymers. In this study, we have attempted to determine if this method for PNS regeneration can be used to study regeneration of axons in the central nervous system (CNS). A 5-mm gap was created in the midthoracic spinal cord of adult rats. Animals were divided into groups in which the gap was bridged with a collagen tube filled with one of two experimental collagen-GAG copolymers or bridged with an unfilled collagen tube. Lesions that were not bridged by a tubular device were included as controls. Rats were sacrificed at 30 days, and spinal cords, including the lesion site, were removed and studied histologically. Large numbers of myelinated axons were observed regrowing within the gap in animals of all groups. The presence of collagen tubes modified the organization and orientation of the fibrous component of reparative tissue and the migration pattern of astrocytes in the wound site. The results suggest that entubulation of the transected spinal cord is a useful technique for studying the substrate preferences of regenerating CNS axons.

Tissue Engineering, 1997

... J. Neurosci. 15, 4109, 1995. 11. Li, S.-T., Archibald, SJ, Krarup, C, and Madison, RD Periphe... more ... J. Neurosci. 15, 4109, 1995. 11. Li, S.-T., Archibald, SJ, Krarup, C, and Madison, RD Peripheral nerve repair with collagen conduits. Clin. ... Exp. Neurol. 88, 762, 1985. 13. Rosen, JM, Padilla, JA, Nguyen, KD, Padilla, MA, Sabelman, EE, and Pham, HN Artificial nerve graft us-361 ...

Tissue Engineering, 1997

... Stone, KR, Rodkey, WR, Webber, RJ, McKinney, L., and Steadman, JR Future directions: Collagen... more ... Stone, KR, Rodkey, WR, Webber, RJ, McKinney, L., and Steadman, JR Future directions: Collagen-based prostheses for meniscal regeneration. ... T. Shearn , Gregory P. Boivin , Cynthia Gooch , Marc T. Galloway , John R. West , Victor S. Nirmalanandhan , Gino Bradica , David L ...

Seminars in Arthritis and Rheumatism, 1992

The formation of synovium-like tissue is a biological response to a loose joint replacement prost... more The formation of synovium-like tissue is a biological response to a loose joint replacement prosthesis. Histological examination of this tissue has shown a synovial lining with a predominance of fibroblasts and macrophages, some multinucleated giant cells, and dispersed particles from the implant. Previous studies have reported elevated interleukin 1 (IL-l), prostaglandin E, (PGE,), and collagenase in this tissue. We developed a canine model for the loose cemented femoral stem. Tissue harvested from the canine model was compared with human tissue retrieved at revision atthroplasty. Histology showed synovium, similar to that observed around loose human prostheses, adjacent to the canine cement sheath. Cells were isolated from this tissue and incubated in culture medium with or without naproxen for 3 days. Aliquots of the conditioned media were tested in the thymocyte

Journal of Orthopaedic Research, 2001

The objective of the study was to evaluate the tissue types filling 4-mm diameter defects in the ... more The objective of the study was to evaluate the tissue types filling 4-mm diameter defects in the canine trochlear groove 1.5, 3, and 6 months after autologous chondrocyte implantation (ACI). Untreated defects served as controls. Periosteum alone controls were also included at the 1.5-month time period. The results were compared with previously published findings obtained 12 and 18 months postoperative. After 3 months the ACI-treated defects contained significantly more reparative tissue than found in the untreated control group, including twice the amount of hyaline cartilage (HC). These findings, however, were the only significant effects of the ACI treatment when compared to the periosteum alone or empty control groups. The benefits of ACI found at 3 months did not persist to longer time periods. An evaluation of the inter-observer error associated with the histomorphometric method indicated that it was generally less than the inter-animal variation in the results.

PubMed, Sep 1, 1989

Clinical experience has shown that deformation of patella components can lead to loosening or exc... more Clinical experience has shown that deformation of patella components can lead to loosening or excessive particulate debris, requiring revision. Factors affecting patella performance are the degree of congruity, the shear forces occurring due to tracking variations, and the excessive patellofemoral forces, particularly at higher flexion angles. A method was devised to load the patella with a constant force against the femoral component. The load was applied through a range of flexion. The deformation and wear patterns resembled those of retrieved clinical specimens. All-plastic components suffered from local deformation and underlying bone failure, whereas metal backing led to eventual penetration of the metal onto the femoral flange. Increased conformity of the patella component onto the femoral flange improved the situation for all-plastic and metal-backed designs by increasing the contact area and the available thickness of plastic.

Journal of Arthroplasty, 1987

One thousand sixty-nine consecutive cemented Kinematic Condylar total knee arthroplasties perform... more One thousand sixty-nine consecutive cemented Kinematic Condylar total knee arthroplasties performed by one group of orthopaedists were studied. The maximum follow-up period was 7 years. Most patients had rheumatoid arthritis or osteoarthritis, and the average patient age was 67 years (range, 12-90 years). Aseptic revisions for loosening were required for only one tibial component and six patella components. Average postoperative flexion was 2.5-107 degrees. The preoperative to postoperative change in range of flexion was not affected by the tilt angle of the tibial component in the sagittal plane. With the use of external alignment guides, the average postoperative alignment was ideal but the standard deviation was high; the standard deviation and the extremes were lower when intramedullary guides were used. There was a 14% incidence of femoral radiolucency and a 30% incidence of tibial radiolucency, which increased only slightly with time. Most radiolucencies on the tibial side were small and restricted to the extreme edges; rarely did radiolucency occur around the central peg. More than one half of the thicker radiolucencies occurred adjacent to wedge-shaped bone defects that were filled with cement.

The Journal of Bone & Joint Surgery, 1997

Articular cartilage has a limited capacity for repair. In recent clinical and animal experiments,... more Articular cartilage has a limited capacity for repair. In recent clinical and animal experiments, investigators have attempted to elicit the repair of defects of articular cartilage by injecting cultured autologous chondrocytes under a periosteal flap (a layer of periosteum). The objective of the present study was to determine the effect of cultured autologous chondrocytes on healing in an adult canine model with use of histomorphometric methods to assess the degree of repair. A total of forty-four four-millimeter-diameter circular defects were created down to the zone of calcified cartilage in the articular cartilage of the trochlear groove of the distal part of the femur in fourteen dogs. The morphology and characteristics of the original defects were defined in an additional six freshly created defects in three other dogs. Some residual noncalcified articular cartilage, occupying approximately 2 per cent of the total cross-sectional area of the defect, was sometimes left in the defect. The procedure sometimes damaged the calcified cartilage, resulting in occasional microfractures or larger fractures, thinning of the zone of calcified cartilage, or, rarely, small localized penetrations into subchondral bone. The forty-four defects were divided into three treatment groups. In one group, cultured autologous chondrocytes were implanted under a periosteal flap. In the second group, the defect was covered with a periosteal flap but no autologous chondrocytes were implanted. In the third group (the control group), the defects were left empty. The defects were analyzed after twelve or eighteen months of healing. Histomorphometric measurements were made of the percentage of the total area of the defect that became filled with repair tissue, the types of tissue that filled the defect, and the integration of the repair tissue with the adjacent cartilage at the sides of the defects and with the calcified cartilage at the base of the defect. In histological sections made through the center of the defects in the three groups, the area of the defect that filled with new repair tissue ranged from a mean total value of 36 to 76 per cent, with 10 to 23 per cent of the total area consisting of hyaline cartilage. Integration of the repair tissue with the adjacent cartilage at the edges of the defect ranged from 16 to 32 per cent in the three groups. Bonding between the repair tissue and the calcified cartilage at the base of the defect ranged from 41 to 89 per cent. With the numbers available, we could detect no significant difference among the three groups with regard to any of the parameters used to assess the quality of the repair. In the two groups in which a periosteal flap was sutured to the articular cartilage surrounding the defect, the articular cartilage showed degenerative changes that appeared to be related to that suturing.

Journal of Orthopaedic Research, 2019

with the execution of the surgical procedures, tissue processing, evaluation and interpretation o... more with the execution of the surgical procedures, tissue processing, evaluation and interpretation of the data, histopathological assessments, and writing of the original draft. M.S. was part of the conceptualization and research design of the study, methodology, evaluation and interpretation of the data, writing of the revision draft, study coordination, administration, supervision of maintaining the integrity of the study, and fund acquisition. M.R.N. was part of the writing of the original draft and revision draft, manuscript preparation and submission, and editorial revisions management. J.W.S. was part of the This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

The Journal of Bone and Joint Surgery

ABSTRACT

Orthopedic Clinics of North America

Revision rates, complication rates, and the bone-cement interface reaction of 1,069 condylar tota... more Revision rates, complication rates, and the bone-cement interface reaction of 1,069 condylar total knee replacements were reviewed to help decide if conventional total knee replacement continues to be appropriate for the older low-demand patient. This knee replacement series was also compared with two published series of total hip replacements from the same institution. The conclusions are (1) in medium-term follow-up, total knee replacement is as good as or superior to total hip replacement and (2) based on bone-cement interface analysis, survival of total knee replacement is expected to be superior to conventional total hip replacement ten years postoperatively.

Clinical Orthopaedics and Related Research

The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro a... more The aseptically loosened prosthesis provided a means for investigating the in vivo and in vitro activity of the cells associated with the loosening process in seven dogs. The cells were isolated and maintained in culture for sufficient periods of time so that their biologic activity could be studied as well as the effect of different agents added to the cells in vivo or in vitro. The biologic response as determined by interleukin-1 and prostaglandin E2 activity paralleled the roentgenographic appearance of loosening and the technetium images and observations made at the time of revision surgery. The correlation between clinical, roentgenographic, histologic, and biochemical loosening indicates that the canine model is suitable for investigating the mechanisms of prosthetic failure. A canine model permits the study of possible nonsurgical therapeutic interventions with the ultimate hope of stopping or slowing the loosening process.

Clinical Orthopaedics and Related Research

The defect made to the level of the tidemark in a canine model has been used in several prior inv... more The defect made to the level of the tidemark in a canine model has been used in several prior investigations of various articular cartilage repair procedures. Direct comparison of the repair method, 15 weeks postoperatively, showed a significant correlation between the degree to which the calcified cartilage layer and subchondral bone were disrupted and the amount of tissue filling. Moreover, when it forms, hyaline cartilage most frequently occurs superficial to intact calcified cartilage. Many of the chondrocytic cells and fibroblasts expressed the gene for a contractile muscle actin, alpha-smooth muscle actin. However, the role of this actin isoform is yet in question. These findings may inform future strategies for cartilage repair.

Restorative neurology and neuroscience, 2001

The purpose of this study was to characterize the effects of implantation of a collagen tube on h... more The purpose of this study was to characterize the effects of implantation of a collagen tube on healing and scar formation following transection of tbc adult rat spinal cord. The spinal cords of adult rats were completely transected at the mid-thoracic level. At 30 days after injury, the cellular and extra-cellular components of repair tissue present within tubulated and non-tubulated (control) wounds were compared using qualitative and quantitative histological techniques. The presence of the tube reduced fibrocollagenous scar invasion into the gap, promoted astrocyte migration, and oriented axonal and connective tissue components of the repair tissue. Tube implants supported the regeneration of a substantial number of myelinated axons. A notable finding was the identification of cells containing a contractile actin isoform in the healing spinal cord. The tubulation model allows for the study of spinal cord wound healing and axon elongation in a controlled experimental environment ...

Wound Repair and Regeneration, 2000

The objective of this study was to evaluate the types of tissue resulting from spontaneous healin... more The objective of this study was to evaluate the types of tissue resulting from spontaneous healing of surgically created defects in adult canine articular cartilage up to 29 weeks postoperatively, with specific attention directed toward the presence and distribution of cells containing the contractile actin isoform, alpha-smooth muscle actin. Two 4-mm diameter defects were made in the trochlear groove to the depth of the tidemark in 20 adult mongrel dogs. The areal percentage of specific tissue types in the reparative material was determined histomorphometrically. Immunohistochemistry was employed to evaluate the percentage of alpha-smooth muscle actin-containing cells. The results showed that approximately 50% of the chondrocytes in the superficial zone of the uninvolved articular cartilage expressed alpha-smooth muscle actin. A significantly lower percentage of alpha-smooth muscle actin-positive chondrocytes appeared in the uninvolved deep zone. Notably, the deep zone adjacent to the defect contained a greater percentage of such cells than in the uninvolved deep zone. Also of interest was that a greater percentage of nonvascular cells in the hyaline cartilage and fibrocartilage of the reparative tissue contained alpha-smooth muscle actin-positive cells, compared to the fibrous tissue in the defects. The findings of this study revealed that canine articular cartilage has some potential for spontaneous regeneration, including integration with the calcified cartilage zone. By 29 weeks, up to 40% of an areal cross section of an untreated full-thickness chondral defect was found to fill with hyaline cartilage, with up to 19% judged histologically similar to articular cartilage. The results warrant further consideration of the role of alpha-smooth muscle actin in chondrocytes in normal articular cartilage and in reparative tissue.

Tissue Engineering Part A, 2013

The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineer... more The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration.

Tissue Engineering Part A, 2012

A multifaceted therapeutic approach involving biomaterial scaffolds, neurotrophic factors, exogen... more A multifaceted therapeutic approach involving biomaterial scaffolds, neurotrophic factors, exogenous cells, and antagonists to axon growth inhibitors may ultimately prove necessary for the treatment of defects resulting from spinal cord injury (SCI). The objective of this study was to begin to lay the groundwork for such strategies by implanting type I collagen scaffolds alone and incorporating individually a soluble Nogo receptor, chondroitinase ABC (ChABC), and mesenchymal stem cells (MSCs) into a standardized 3-mm-long hemiresection defect in the rat spinal cord. Statistically significant improvement in hindlimb motor function between the first and fourth weeks post-SCI was recorded for the scaffold-alone group and for the ChABC and MSC groups, but not the control group. Four weeks post-SCI, the scaffolds appeared intact with open pores, which were infiltrated with host cells. Of note is that in some cases, a few growth-associated protein 43 (GAP-43)-positive axons were seen reaching the center of the scaffold in the scaffold-alone and ChABC groups, but not in control animals. Angiogenic cells were prevalent in the scaffolds; however, the number of both macrophages and angiogenic cells in the scaffolds was significantly less than in the control lesion at 4 weeks. The results lay the foundation for future dose-response studies and to further investigate a range of therapeutic agents to enhance the regenerative response in SCI.

Tissue Engineering, 1998

... and Women's Hospital, Harvard Medical School, Boston, Massachusetts; presented at th... more ... and Women's Hospital, Harvard Medical School, Boston, Massachusetts; presented at the inaugural meeting of the Tissue Engineering Soci-ety, Orlando, Florida, December ... 22. Ohlsen, L., and Widenfalk, B. The early development of articular cartilage after perichondrial grafting ...

Tissue Engineering, 2001

Lapine and canine marrow stromal cells were found to contain a contractile actin isoform, alpha-s... more Lapine and canine marrow stromal cells were found to contain a contractile actin isoform, alpha-smooth muscle actin (SMA), by immunohistochemistry and Western blot analysis. The SMA was found to be incorporated into stress fibers that were prominently displayed by the cells in monolayer culture. The cell content of this actin isoform increased with passage number. The contractility of SMA-expressing stromal cells was demonstrated by their contraction of collagen-glycosaminoglycan analogs of extracellular matrix into which they were seeded. The demonstration that marrow-derived stromal cells express the SMA gene may explain recent findings of this expression in musculoskeletal connective tissue cells including osteoblasts, chondrocytes, and fibrochondrocytes that may be derived from this mesenchymal stem cell. The implications of these findings for tissue engineering strategies employing marrow stromal cells are also discussed.

Tissue Engineering, 1997

ABSTRACT In previous studies, we have examined the substrate preferences of peripheral nervous sy... more ABSTRACT In previous studies, we have examined the substrate preferences of peripheral nervous system (PNS) axons elongating within a 15-mm gap in the rat sciatic nerve. Gaps were bridged with tubes filled with one of several porous collagen-glycosaminoglycan (GAG) copolymers. In this study, we have attempted to determine if this method for PNS regeneration can be used to study regeneration of axons in the central nervous system (CNS). A 5-mm gap was created in the midthoracic spinal cord of adult rats. Animals were divided into groups in which the gap was bridged with a collagen tube filled with one of two experimental collagen-GAG copolymers or bridged with an unfilled collagen tube. Lesions that were not bridged by a tubular device were included as controls. Rats were sacrificed at 30 days, and spinal cords, including the lesion site, were removed and studied histologically. Large numbers of myelinated axons were observed regrowing within the gap in animals of all groups. The presence of collagen tubes modified the organization and orientation of the fibrous component of reparative tissue and the migration pattern of astrocytes in the wound site. The results suggest that entubulation of the transected spinal cord is a useful technique for studying the substrate preferences of regenerating CNS axons.

Tissue Engineering, 1997

... J. Neurosci. 15, 4109, 1995. 11. Li, S.-T., Archibald, SJ, Krarup, C, and Madison, RD Periphe... more ... J. Neurosci. 15, 4109, 1995. 11. Li, S.-T., Archibald, SJ, Krarup, C, and Madison, RD Peripheral nerve repair with collagen conduits. Clin. ... Exp. Neurol. 88, 762, 1985. 13. Rosen, JM, Padilla, JA, Nguyen, KD, Padilla, MA, Sabelman, EE, and Pham, HN Artificial nerve graft us-361 ...

Tissue Engineering, 1997

... Stone, KR, Rodkey, WR, Webber, RJ, McKinney, L., and Steadman, JR Future directions: Collagen... more ... Stone, KR, Rodkey, WR, Webber, RJ, McKinney, L., and Steadman, JR Future directions: Collagen-based prostheses for meniscal regeneration. ... T. Shearn , Gregory P. Boivin , Cynthia Gooch , Marc T. Galloway , John R. West , Victor S. Nirmalanandhan , Gino Bradica , David L ...

Seminars in Arthritis and Rheumatism, 1992

The formation of synovium-like tissue is a biological response to a loose joint replacement prost... more The formation of synovium-like tissue is a biological response to a loose joint replacement prosthesis. Histological examination of this tissue has shown a synovial lining with a predominance of fibroblasts and macrophages, some multinucleated giant cells, and dispersed particles from the implant. Previous studies have reported elevated interleukin 1 (IL-l), prostaglandin E, (PGE,), and collagenase in this tissue. We developed a canine model for the loose cemented femoral stem. Tissue harvested from the canine model was compared with human tissue retrieved at revision atthroplasty. Histology showed synovium, similar to that observed around loose human prostheses, adjacent to the canine cement sheath. Cells were isolated from this tissue and incubated in culture medium with or without naproxen for 3 days. Aliquots of the conditioned media were tested in the thymocyte

Journal of Orthopaedic Research, 2001

The objective of the study was to evaluate the tissue types filling 4-mm diameter defects in the ... more The objective of the study was to evaluate the tissue types filling 4-mm diameter defects in the canine trochlear groove 1.5, 3, and 6 months after autologous chondrocyte implantation (ACI). Untreated defects served as controls. Periosteum alone controls were also included at the 1.5-month time period. The results were compared with previously published findings obtained 12 and 18 months postoperative. After 3 months the ACI-treated defects contained significantly more reparative tissue than found in the untreated control group, including twice the amount of hyaline cartilage (HC). These findings, however, were the only significant effects of the ACI treatment when compared to the periosteum alone or empty control groups. The benefits of ACI found at 3 months did not persist to longer time periods. An evaluation of the inter-observer error associated with the histomorphometric method indicated that it was generally less than the inter-animal variation in the results.