Characterization of a new degradable polymer scaffold for regeneration of the dermis: In vitro and in vivo human studies.

Full thickness skin wounds in humans heal with scars, but without regeneration of the dermis. A degradable poly(urethane urea) scaffold (PUUR), Artelon(R) is already used to reinforce soft tissues in orthopaedics, and for treatment of osteoarthritis of the hand, wrist and foot. In this paper we have done in vitro experiments followed by in vivo studies to find out whether the PUUR is biocompatible and usable as a template for dermal regeneration. Human dermal fibroblasts were cultured on discs of PUUR, with different macrostructures (fibrous and porous). They adhered to and migrated into the scaffolds, and produced collagen. The porous scaffold was judged more suitable for clinical applications and 4 mm Ø, 2 mm-thick discs of porous scaffold (12% w/w or 9% w/w polymer solution) were inserted intradermally in four healthy human volunteers. The implants were well tolerated and increasing ingrowth of fibroblasts was seen over time in all subjects. The fibroblasts stained immunohistochemically for procollagen and von Willebrand factor, indicating neocollagenesis and angiogenesis within the scaffolds. The PUUR scaffold may be a suitable material to use as a template for dermal regeneration.

Construction of skeletal myoblast-based polyurethane scaffolds for myocardial repair.

Intramyocardial transplantation of skeletal myoblasts augments postinfarction cardiac function. However, poor survival of injected cells limits this therapy. It is hypothesized that implantation of myoblast-based scaffolds would result in greater cell survival. Rat skeletal myoblasts were seeded on highly porous polyurethane (PU) scaffolds (7.5 x 7.5 x 2.0 mm). The effect of several scaffold pretreatments, initial cell densities, and culture periods was tested by DNA-based cell count and viability assessment. Seeded PU scaffolds were implanted on infarcted hearts and immunohistology was performed 4 weeks later. Precoating with laminin allowed the most favorable cell attachment. An initial inoculation with 5 x 10(6) cells followed by a 15-day culture period resulted in optimal myoblast proliferation. Four weeks after their implantation in rats, numerous myoblasts were found throughout the seeded patches although no sign of differentiation could be observed. This myoblast seeding technique on PU allows transfer of a large number of living myoblasts to a damaged myocardium.

The inflammatory cell influx and cytokines changes during transition from acute inflammation to fibrous repair around implanted materials.

The inflammatory and fibrous responses in a subcutaneous rat model were evaluated around degradable polyurethane urea (PUUR; Artelon), with titanium and tissue culture polystyrene (PS) discs having different surface chemical properties but similar surface topography. Cytokines, viability, cellular response, differentiation of cells and fibrous capsule formation and vascularization was investigated after 1, 7 and 21 days of implantation. The exudates retrieved from the pockets were analysed with respect to the total cell numbers, the proportions of cell types, the differentiation of monocytes/macrophages (ED1, ED2), the DNA content and the viability (LD, Trypan blue). Tumour necrosis factor alpha ((h)TNF-alpha) and interleukin-10 ((h)IL-10) were quantified by ELISA. The number of blood vessels, blood vessel luminal area, blood vessel distribution and the fibrous capsule thickness were analysed. The highest number of cells in the exudates around all implants was detected during the early phase of healing (1-7 days). The proportion of ED2-positive cells in the exudates increased from 2-8% at 1 day to 43-56% at 21 days. The levels of TNF-alpha were low with a decrease at 7 days. After 21 days high amounts of IL-10 in the exudates were detected, in particular around PUUR. This study shows that the transition from inflammation to repair (1-21 days) around PUUR, Ti and PS materials was characterized by a decrease in inflammatory cell influx, an increasing proportion of ED2-expressing macrophages, a biphasic TNF-alpha secretion, an increase of IL-10 and a fibrous capsule formation similar to all materials tested.

Results from a degradable TMC joint Spacer (Artelon) compared with tendon arthroplasty.

PURPOSE: A new spacer for the trapeziometacarpal joint (TMC) based on a biological and tissue-preserving concept for the treatment of TMC osteoarthritis (OA) has been evaluated. The purpose was to combine a spacing effect with stabilization of the TMC joint. METHODS: Artelon (Artimplant AB, Sweden) TMC Spacer is synthesized of a degradable polyurethaneurea (Artelon), which has been shown to be biocompatible over time and currently is used in ligament augmentation procedures. Fibers of the polymer were woven into a T-shaped device in which the vertical portion separates the bone edges of the TMC joint and the horizontal portion stabilizes the joint. Fifteen patients with disabling pain and isolated TMC OA were included in the study. Ten patients received the spacer device and the remaining 5 (control group) were treated with a trapezium resection arthroplasty with abductor pollicis longus (APL) stabilization. The median ages of the 2 groups were 60 and 59 years, respectively. Pain, strength, stability, and range of motion were measured before and after surgery. Radiographic examination was performed in all patients before and after surgery. At follow-up evaluation 3 years after surgery an unbiased observer evaluated all patients. Biopsy specimens were obtained from 1 patient 6 months after surgery. RESULTS: All patients were stable clinically without signs of synovitis. In both groups all patients were pain free. The median values for both key pinch and tripod pinch increased compared with before surgery in the spacer group but not in the APL group. The biopsy examinations showed incorporation of the device in the surface of the adjacent bone and the surrounding connective tissue. No signs of foreign-body reaction were seen. CONCLUSIONS: This study showed significantly better pinch strength after Artelon TMC Spacer implantation into the TMC joint compared with APL arthroplasty.

Resorbable and nonresorbable hydroxyapatite granules as bone graft substitutes in rabbit cortical defects.

BACKGROUND: The use of various synthetic calcium phosphate compositions for the promotion of bone in bone defects is of potential interest because such materials may be tailor made and may bond to bone. There is yet an inadequate knowledge of the role of calcium phosphate composition and resorbability for the bone response. PURPOSE: The aim of the present study was to compare the ability of resorbable versus nonresorbable hydroxyapatite (HA) granules to promote new bone formation in cortical bone defects. Resorbable and nonresorbable HA granules, used as bone graft substitutes, were evaluated after 6 weeks and 3 months in the rabbit tibia. Circular defects (diameter 5.0 mm) were made in both tibias of 18 New Zealand white rabbits. The 36 defects were divided into three groups (six observations per group and time, respectively). The first group was augmented with resorbable HA granules, the second group was augmented with ceramic nonresorbable HA granules, and the third group was left without augmentation (control). The animals were killed after 6 weeks and 3 months, and the tissue was evaluated with light microscopic (LM) morphology and morphometry, scanning electron microscopy (SEM), and energy dispersive x-ray analysis (EDX). RESULTS: After 3 months LM morphometry revealed significantly more newly formed bone in the two HA augmented groups compared with that in the control. A close contact was found between both kinds of HA granules and new bone as viewed with light microscopy and SEM. A relatively slow degradation process was indicated by the small reduction of the total granule area in the cortical defects. However, LM observations showed a change of granule form. Pilot experiments using SEM-EDX indicate that Ca and P contents had decreased in the resorbable HA granules between 6 weeks and 3 months. Further, a higher content of Ca and P was found in the newly formed bone close to granules, in comparison with more distant newly formed bone. CONCLUSIONS: Our results suggest that both resorbable and nonresorbable HA granules promote new bone formation in rabbit cortical defects, which does not occur in control defects.

Studies of polyurethane urea bands for ACL reconstruction.

The present report describes the mechanical tests, in vitro and in vivo studies of a poly(urethane urea) (PUUR) intended for clinical use in anterior cruciate ligament (ACL) reconstruction. In the mechanical tests, no evidence of severe fatigue was observed after repeated cyclic loading. Testings for mutagenicity and delayed contact hypersensitivity were found negative. Three in vivo studies were performed in rabbits and minipigs. Altogether 35 rabbits were operated upon in (1) an intraarticular implantation study, performed to evaluate the soft tissue response to woven bands and fiber bundles of PUUR and (2) a rabbit ACL study, examining the function of the PUUR ACL replacement and the tissue response to the material. In a third study, PUUR ACL replacement in minipigs was evaluated. Taken together, ingrowth of connective tissue in close contact with the PUUR fibers was detected both in rabbits and minipigs. The first clear histological signs of degradation of the polymer was detected after 24 months. In conclusion, the evaluated mechanical properties of the PUUR band correspond to those of the mature, human ACL. Furthermore, both from a histological and functional point of view, the PUUR woven band show interesting properties for future clinical ACL reconstructions.