Vascularized Bone Transplantation Research Articles

3D printing of bone and cartilage with polymer materials.

Damage and degeneration to bone and articular cartilage are the leading causes of musculoskeletal disability. Commonly used clinical and surgical methods include autologous/allogeneic bone and cartilage transplantation, vascularized bone transplantation, autologous chondrocyte implantation, mosaicplasty, and joint replacement. 3D bio printing technology to construct implants by layer-by-layer printing of biological materials, living cells, and other biologically active substances in vitro, which is expected to replace the repair mentioned above methods. Researchers use cells and biomedical materials as discrete materials. 3D bio printing has largely solved the problem of insufficient organ donors with the ability to prepare different organs and tissue structures. This paper mainly discusses the application of polymer materials, bio printing cell selection, and its application in bone and cartilage repair.

Standardized and axially vascularized calcium phosphate-based implants for segmental mandibular defects: A promising proof of concept

The reconstruction of massive segmental mandibular bone defects (SMDs) remains challenging even today; the current gold standard in human clinics being vascularized bone transplantation (VBT). As alternative to this onerous approach, bone tissue engineering strategies have been widely investigated. However, they displayed limited clinical success, particularly in failing to address the essential problem of quick vascularization of the implant. Although routinely used in clinics, the insertion of intrinsic vascularization in bioengineered constructs for the rapid formation of a feeding angiosome remains uncommon.In a clinically relevant model (sheep), a custom calcium phosphate-based bioceramic soaked with autologous bone marrow and perfused by an arteriovenous loop was tested to regenerate a massive SMD and was compared to VBT (clinical standard). Animals did not support well the VBT treatment, and the study was aborted 2 weeks after surgery due to ethical and animal welfare considerations. SMD regeneration was successful with the custom vascularized bone construct. Implants were well osseointegrated and vascularized after only 3 months of implantation and totally entrapped in lamellar bone after 12 months; a healthy yellow bone marrow filled the remaining space. Statement of significanceRegenerative medicine struggles with the generation of large functional bone volume. Among them segmental mandibular defects are particularly challenging to restore. The standard of care, based on bone free flaps, still displays ethical and technical drawbacks (e.g., donor site morbidity).Modern engineering technologies (e.g., 3D printing, digital chain) were combined to relevant surgical techniques to provide a pre-clinical proof of concept, investigating for the benefits of such a strategy in bone-related regenerative field.Results proved that a synthetic-biologics-free approach is able to regenerate a critical size segmental mandibular defect of 15 cm3 in a relevant preclinical model, mimicking real life scenarii of segmental mandibular defect, with a full physiological regeneration of the defect after 12 months.

English

BACKGROUND Nutrient foramen is a large opening that transfers the arteries that supply the bone to the bone cavity. During surgical procedures, it is very important to have precise and complete information about the location of the foramina to determine whether the fracture line passes close to the nutrient foramina. The purpose of this study was to determine the number and position of the femoral nutrient foramina together with morphometric measurements. METHODS A total of 93 dry adult femurs with unknown sexes were examined in this study. The direction, location and the total number of nutrient foramina of the femur were investigated by using an anthropometer (Lafayette instrument, Indiana). Also, foraminal index was calculated. RESULTS The analysis revealed that 28 (53.8 %) of the femurs with a single nutrient foramen were on the right side and 22 (53.7 %) were on the left side, respectively. Femurs with double nutrient foramina were 23 (44.2 %) and 18 (43.9 %) on right and left sides, respectively. Femurs with triple nutrient foramina were 1(1.9 %) and 1 (2.4 %) on right and left sides, respectively. The foraminal index of femurs was found as (41, 58 %) and (42, 23 %) on the right and left sides, respectively. The nutrient foramen was mostly 84 (90.3 %) located at the middle third of the femur. CONCLUSIONS The findings of this study provide information and details about nutrient foramen which have clinical importance, especially in surgical procedures like bone grafting and microsurgical vascularized bone transplantation. KEY WORDS Femur, Foraminal Index, Nutrient Artery, Nutrient Foramina

Essential Oils for Bone Repair and Regeneration-Mechanisms and Applications.

Although bone possesses a remarkable capacity for self-remodeling and self-healing of small defects, the continuously increasing growth of bone diseases in the elderly population is becoming a significant burden, affecting individual life quality and society. Conventional treatment options involve surgical procedures for repair and reconstruction, local debridement, autografts or allografts, bone transport, Masquelet’s two-stage reconstructions, and vascularized bone transplants. However, as such approaches often lead to disruptions of bone-regeneration processes and microbial contaminations and are often inefficient, researchers focus on developing bone-regenerative strategies and identifying novel therapeutic agents that could aid the bone-healing process. In this regard, plant-derived biocompounds, especially essential oils (EOs), have received great scientific attention in recent years, owing to their antioxidant, anti-inflammatory, and antimicrobial effects. Current studies focus on either the direct application of EOs on bone tissue or the introduction of EOs as bioactive compounds in bone scaffolds or as coatings for bone implants. Some of the EOs investigated involve St. John’s wort, rosemary, thyme, ylang, white poplar, eucalyptus, lavender, and grape seed. In this context, the present paper aims to provide an overview of the main mechanisms involved in bone repair and regeneration and the potential of EOs to address and enhance these mechanisms.

Anatomical study of nutrient foramina in humerus

Introduction: Knowledge of nutrient foramina is important in surgical procedures. Objective of present study is to know the number, location and direction of nutrient foramina in diaphysis of humerus and to test the significant difference of total length and foraminal index on right and left side separately. Materials and Methods: Total 100 dried humerii of unknown sex (52 of right and 48 of left side) were taken for present study. The identification of nutrient foramen was confirmed with the help of magnifying lens and metallic wire. The total length of humerus and distance of nutrient foramen from proximal end of humerus was measured by sliding caliper and osteometric board. Foraminal index was also calculated. Results: All the examined bones showed single diaphyseal nutrient foramen. Majority of foramina (81%) were present on middle 1/3 of anteromedial surface of shaft of humerus. The direction of these foramina was similarly found in all bones i.e. towards the elbow joint. There were no significant differences between right and left side for total length and foraminal index. Conclusion: An accurate knowledge of the location of nutrient foramina is important in surgical procedures like reduction of fracture, bone grafting and microsurgical vascularized bone transplantation. Keywords: Humerus, Nutrient foramina, Number, Location, Direction, Foraminal index.

Variation in number and position of nutrient foramen of clavicle – A morphological study in western Rajasthan

Introduction: The clavicle is a modified long bone. It is the most important bone for transmission of weight from upper limb to the axial skeleton. It supports the shoulder so that the arm can swing clearly away from the trunk. Materials and Methods: The study included 102 adult clavicles 52 right sides and 52 left side which were obtained from the department of the Anatomy Dr. S.N. Medical College Jodhpur. The age and sex of the clavicles were not determined. All the bones were grossly observed for the number, location and direction of the nutrient foramina. The data were collected and morphologically analysed. Results: In our Present study Nutrient foramina were present in 50 clavicles (Right) and 44 clavicles (left). Out of which single foramina in 41 clavicles (Right) and 36 clavicles (Left), double foramina in 9 clavicles (Right) and 6 clavicles (left) and three foramina in 2 clavicles (Left). Absence of nutrient foramina were found in 2 clavicles (Right) and 8 clavicles (Left). Maximum number was present in the medial 2/3 and on the posterior surface of 46 bones (Right) and 34 Bones (Left). All foramina were directed towards the acromial end. Conclusion: The knowledge of nutrient foramina in clavicles is important for surgical procedures such as bone grafting and in microsurgical vascularized bone transplantation. Keywords: Nutrient foramina, Clavicle, Bone graft.

A Study of Variation of Nutrient Foramen of Dry Adult Humerus

Introduction: Nutrient artery is the chief artery for the blood supply of the long bone and passes through the nutrient foremen which lie towards the medial border in the anteromedial surface below the midpoint in humerus. During the surgical procedures like bone grafting and microsurgical vascularized bone transplantation, the knowledge of nutrient foramen is important. The nutrient artery plays an important role in nonunion and delayed union of fracture bone.
 Aims and Objectives: The aim of this study is to determine the number, position and direction of the nutrient foramina of humerus.
 Materials and Methods: 50 humerus, 21 of right and 29 of left side were studied without any pathological disorders.
 Results: Single nutrient foremen was observed in 80% humerus. Double foramen in 16%. There was no foramen in 4% humerus. It was also concluded that 88% humerus had the nutrient foremen in anteromedial surface. Nutrient foremen were dominant in Zone II with 82%. All foramen were directed towards the lower end of humeri.
 Conclusion: The presence of single foramen in the zone II was dominant. The nutrient foramina were also dominant in the anteromedial surface of the humerus.

A Study on Variations of Nutrient Foramen of Fibula in Saurashtra Region with its Clinical Relevance

Introduction: Nutrient foramen is an opening into shaft of fibula which gives passage to the blood vessels of medullary cavity. The knowledge of nutrient foramen is important in surgical procedures like bone grafting and more recently in microsurgical vascularized bone transplantation. Objective: To determine the number, location and direction of nutrient foramen and whether the nutrient foramens obey the rule of ossification, that is directed away from the growing end of the bone or not.  Subjects and Methods: The present study consisted of 150 (75 right and 75 left) dried fibula bones excluding any fracture or pathological abnormalities Number and direction of nutrient foramen was observed in each fibula. Location of nutrient foramen in relation with surfaces and zones of fibula was determined. Results: It has been observed that 96.67% of the fibula had a single nutrient foramen, 3.33% double foramen and no bone had 0 nutrient foramen. It was concluded that 98.71% of the nutrient foramina were present on the posterior surface and 1.29 % on medial crest. It was also concluded that most (98.06%) of the foramina present in the zone II followed by zone III (1.29%) then by zone I (0.65%). All foramina were directed toward the upper end of fibula. Conclusion: By knowing the number and location of the nutrient foramina in fibula would be useful in preventing intra-operative injury of nutrient artery during orthopedic, plastic and reconstructive surgery and will also be relevant in medico legal practice.

Prefabrication of a large pedicled bone graft by engineering the germ for de novo vascularization and osteoinduction

Large and complex bone defects represent challenging clinical scenarios, typically requiring autologous vascularized bone transplants. In order to bypass the numerous associated limitations, here we aimed at ectopically prefabricating a bone graft surrogate with vascular pedicle.A hollow cylinder of devitalized cancellous bone was used to define the space of a large bone substitute. This space was filled with devitalized pellets of engineered hypertrophic cartilage as bone-inducing material, in combination or not with stromal vascular fraction (SVF) of adipose tissue as source of osteoprogenitors and endothelial cells. Vascularization of the space was targeted through axial insertion of an arterio-venous (AV) bundle. Constructs were subcutaneously implanted in nude rats for 12 weeks and analyzed for bone formation and vascularization by histology and microtomography.Retrieved constructs were extensively vascularized in all conditions, with vessels sprouting from the AV bundle and reaching a higher density in the axially central volume. Bone tissue was formed through remodeling of hypertrophic cartilage, and quantitatively correlated with de novo vascularization.Our study demonstrates feasibility to prefabricate large, pedicled bone grafts in predefined shapes. The combination of an AV bundle with engineered hypertrophic cartilage provided a germ for the coupled processes of vascularization and bone formation. The demonstrated osteoinductivity of devitalized hypertrophic cartilage offers the opportunity of implementing the proposed regenerative surgery strategy through off-the-shelf materials.

Strategy and discussion of hip joint preserving surgery treatments for adult osteonecrosis of the femoral head

As a common disease in orthopedics, osteonecrosis of the femoral head (ONFH) frequently occurs among young and middle-aged people. Hip joint preserving surgery has attracted more and more attention due to the fact that artificial joint prosthesis has a certain useful life and the rate of hip joint revision is high and the higher risk of many complications. There are a large number of operative methods for preserving hip joint in clinical practice without definitive effectiveness. How to choose appropriate surgical methods at the right time is also a continuous understanding. The pathological process of necrosis of the femur helps to choose the choice of the femoral head necrosis for the treatment of hip operation. Core decompression and impaction bone grafting with simple operative methods can relieve internal pressure of femoral head and pain symptoms, but they cannot remove necrotic bone completely. Hence, they are only used for ONFH in the early stage. Vascularized bone transplantation can fill defects of the former, as it can not only completely remove necrotic bone, but also provide bone graft with nourishing vessels for femoral head, being beneficial to reconstruct the bone structure of femoral head. Subsequently, the application of tantalum rod can provide mechanical support for femoral head to prevent the collapse of femoral head. Hip joint preserving surgery, in recent years, has been performed increasingly, and has obtained improvement in clinical effects. The multiple combination of a variety of its operative methods provides more effective treatments for ONFH. It is an essential notion that hip joint preserving surgery, however with any operative method, should as far as possible select a surgical plan with little trauma, simple methods, and little injury of hip joint bone structure based on ensuring the effectiveness.

The study of establishing the chimerism through vascularized ilium transplantation animal model

Objective To construct an animal model of vascularized iliac bone transplantation which could establish the immune chimerism. Methods The experiment was divided into three groups. In experiment group we slected the male SD rats as donors and the female SD rats as recipients. Then the experiment group was performed the improved vascularized ilium transplantation operation. The positive group was male SD rats without handling. The negative group was female SD rats without handling. On the twenty-eighth day after surgery, the rat SRY gene was detected by PCR. Dynamically monitoring the changes of the ratio of CD4+/CD8+ T cells by flow cytometry after operation. Dynamically monitoring the changes of the levels of serum IL-2 by enzyme linked immunosorbent assay after operation. Imaging and pathology were used to detect the transplanted iliac bone. Results Ten transplantations were performed in the experiment group and 7 flaps survived with a successful rate of 73 %.SRY gene was detected in female rats that receive the male rats' iliac bone transplantation by PCR in the experiment group. After Micro-CT scanning and three-dimensional reconstruction, it showed that the transplanted iliac bone mineral density was decreased. Comparing rats that establish the chimerism with normal rats, the ratio of CD4+/CD8+ T cells and the levels of serum IL-2 had no difference. Pathological results showed that the transplanted iliac bone of rats with chimerism were normal and the rats without chimerism were necrotic. Conclusions From the improved vascularized ilium transplantation operation, we successfully detected the SRY gene in female rats which received the male rats' iliac bone transplantation. It proved that the improved vascularized ilium transplantation operation could establish the chimerism. Through the immunosuppressant, the immune status of the rat after operation was well. Key words: Vascularized iliac bone transplantation; Animal model; Chimerism

Past decade on hip-preserving surgery for osteonecrosis of femoral head treatment in China

As a common disease in orthopedics, osteonecrosis of the femoral head (ONFH) frequently occurs among young and middle-aged people. Hip joint preserving surgery has attracted more and more attention due to the fact that artificial joint prosthesis has a certain useful life and the rate of hip joint revision is high and the higher risk of many complications. There are a large number of operative methods for preserving hip joint in clinical practice without definitive curative effects. Core decompression and impaction bone grafting with simple operative methods can relieve internal pressure of femoral head and pain symptoms, but they cannot remove necrotic bone completely. Hence, they are only used for ONFH in the early stage. Vascularized bone transplantation can fill defects of the former, as it can not only completely remove necrotic bone, but also provide bone graft with nourishing vessels for femoral head, being beneficial to reconstruct the bone structure of femoral head. Subsequently, the application of tantalum rod can provide mechanical support for femoral head to prevent the collapse of femoral head. The emergence of stem cell transplantation has created a new approach to preserve hip joint for ONFH, which promotes the regeneration of bone cells and assists femoral head in repair, often combined with other operative methods and using characteristics of superior proliferation and differentiation of stem cells. Hip joint preserving surgery, in recent years, has been performed increasingly, and has obtained improvement in clinical effects. The multiple combination of a variety of its operative methods provides more effective treatments for ONFH. It is an essential notion that hip joint preserving surgery, however with any operative method, should as far as possible select a surgical plan with little trauma, simple methods and little injury to bone structure of hip joint based on ensuring the efficacy.

Anatomical variation in position, direction, and number of nutrient foramina in clavicles

Background: The clavicle is a modified long bone. It is the most important bone for transmission of weight from upper limb to the axial skeleton and for muscle attachments and is significant source for bone grafting. Objective: To determine the position, direction, and number of nutrient foramina in human clavicles. Materials and Methods: The study comprised 50 clavicles of unknown sex, which were obtained from the Department of Anatomy, Smt. BK Shah Medical Institute & Research Centre, Piparia, Vadodara, Gujarat, India. The foramen index was calculated using the Hughes formula. Results: The nutrient foramen was observed in all 50 (100%) clavicles. Total 82 foramina were observed. In 18.3% clavicles, nutrient foramen was present at medial 1/3rd region, in 72% at the middle 1/3rd, and in 9.8% at the lateral 1/3rd. Single foramen was present in 21(42%) clavicles & double foramina in 26 (52%) clavicles. The nutrient foramen was found on inferior surface in 49.2% clavicles and on posterior surface in 50.8% clavicles. The average distance of the foramen from the sternal end was 69.8 mm (6.98 cm) and the mean foraminal index was 49.01. Conclusion: The knowledge of nutrient foramina in clavicles is important in surgical procedures such as bone grafting and in microsurgical vascularized bone transplantation.

Anatomical study of diaphyseal nutrient foramina in human adult humerus

Purpose: The objective of the following study is to determine the variation in diaphyseal nutrient foramen (NF) of humerus with respect to their number, location, direction and size. Materials and Methods: The present study was conducted on 100 humeri. The number and direction of diaphyseal NF were observed in all bones with the help of a hand lens. Position was described into horizontal and vertical zones; caliber was determined using hypodermic needles. Foraminal index was also calculated. Results: The mean length of humerus observed in the present study was 30.7 cm. The NF was situated at 17.8 cm from the proximal end, 12.4 cm from the distal end and ~2.9 cm below the mid length of humerus. The mean foramina index and circumference of NF was 57.7 and 6.2 cm respectively. Majority of the humeri (77%) had single NF while in 3% of humeri NF was absent. Middle one-third and on the antero-medial surface of the humerus was the most common location of the foramen. Majority of the dominant foramen was large in size and all were directing toward the distal end. Conclusion: The results of the present investigation indicate that there is variation in the number, location and size of NF in humeri among Indian population. An accurate knowledge of the location of the NF in long bones can be useful in certain surgical procedures such as bone grafting, microsurgical vascularized bone transplantation and in fractures.

Cell lineage in vascularized bone transplantation.

The biology behind vascularized bone allotransplantation remains largely unknown. We aim to study cell traffic between donor and recipient following bone auto-, and allografting. Vascularized femoral transplantation was performed with arteriovenous bundle implantation and short-term immunosuppression. Twenty male Piebald Virol Glaxo (PVG; RT1(c) ) rats received isotransplants from female PVG (RT1(c) ) rats and 22 male PVG rats received allografts from female Dark Agouti rats (DA, RT1(a) ), representing a major histocompatibility mismatch. Both groups were randomly analyzed at 4 or 18 weeks. Bone remodeling areas (inner and outer cortical samples) were labeled and laser capture microdissected. Analysis of sex-mismatch genes by real-time reverse transcription-polymerase chain reaction provided the relative Expression Ratio (rER) of donor (female) to recipient (male) cells. The rER was 0.456 ± 0.266 at 4 weeks and 0.749 ± 0.387 at 18 weeks (p = 0.09) in allotransplants. In isotransplants, the rER was 0.412 ± 0.239 and 0.467 ± 0.252 at 4 and 18 weeks, respectively (p = 0.21). At 4 weeks, the rER at the outer cortical area of isotransplants was significantly lower in isotransplants as compared with allotransplants (0.247 ± 0.181 vs. 0.549 ± 0.184, p = 0.007). Cells in the inner and outer cortical bone remodeling areas in isotransplants were mainly donor derived (rER < 0.5) at 18 weeks, whereas allotransplants contained mainly recipient-derived cells (rER > 0.5) at 18 weeks. Applying novel methodology, we describe detailed cell traffic in vascularized bone transplants, elaborating our comprehension on bone transplantation.

Long-term effects of vascularized pisiform transfer for Kienb(o)ck's disease

Objective To evaluate the long-term efficacy of vascularized pisiform transfer for patients with Kienb(o)ck's disease in Lichtman stages Ⅲ-Ⅳ. Methods Eleven patients were reviewed to analyze results after lunate resection and vascularized pisiform transfer for Lichtman stages Ⅲ and Ⅳ. There were six men and five women. Age ranged from 20 to 67 years with a average of 41.0±14.3 years. According to Lichtman stage. There were 4 cases in stage Ⅲa, 5 cases in stage Ⅲb, and 2 cases in stage Ⅳ. Assessment criteria included subjective assessment of pain, visual analogue scale (VAS), range of motion (ROM), grip power,Cooney wrist score and radiographic changes on each follow-up visit. The radiographic changes including pis iform bone location, shape, sclerosis change, osteoarthritis, carpal height ratio, Nattrass index, Radioscaphoid angle and ulnar variance were recorded. Results The follow-up periods of all of cases were 61-202 months,with an average of 104.1 months. Pain had improved in 10 patients and disappeared in 7 cases. The VAS score was 2.2±1.9 at follow-up visit. Range of motion of injured wristw as only 65.3% of opposite side. Grip power was 84.3% of the contralateral hand. According to Cooney score, the results were excellent in 1 case, good in 7cases, fair in 2 cases and poor in 1 case, with the excellent and good rate of 72.7%. Radiologically, 8 cases had normal position of the pisiform bone, 2 had volar displacement and 1 had ulnar displacement which leaded to widen scaphopisiform space. Six pisiform bones had normal trabecular structure, three had degenerative changes. Bone sclerosis was seen in 2 cases and osteoarthritis was found in 3 patients. Compared with radiographic parameter before surgery, carpal height ratio and Nattrass index significantly lowered and radioscaphoid angle significantly increased. Conclusion Lunate resection and vascularized pisiform transfer is an effective method for Kienb(o)k′s disease in stages Ⅲ-Ⅳ. Although carpal collapse appeared postoperatively,the results show high patient satisfaction and good function after vascularized bone transplantation. Key words: Lunate bone; Pisiform bone; Osteonecrosis; Bone transplantation

The Muscular and the New Osteomuscular Composite Peroneus Brevis Flap: Experiences from 109 Cases

Pedicled peroneus brevis muscles are proven flaps for defect coverage around the ankle, foot, and distal lower leg. Some of these defects--such as postosteitic hollowed out calcaneal bones--may profit from a simultaneous vascularized bone transplantation. The authors' experiences with 109 successive muscular and newly developed osteomuscular peroneus flaps are outlined for small to medium combined defects in this region. One hundred nine patients with various soft-tissue and skeletal defects underwent reconstruction with proximally (n = 10) or distally pedicled (n = 98) or free microvascular transplanted (n = 1) peroneus brevis flaps. Eight patients received a composite flap of the peroneus brevis muscle with an attached lateral split fibula segment. In 72.5 percent of the cases, a stable defect closure was achieved without significant secondary procedures. In 16.5 percent, further operations such as secondary wound closure or flaps were necessary, most often because of the avascular loss of the 1 to 3 cm of the distal flap tip. Nine flaps (8.3 percent) were lost completely. Seven of eight osteomuscular flaps demonstrated stable bony healing, and full weight bearing was achieved. No relevant donor-site complications were seen. The peroneus brevis is a valuable flap for defect closure around the ankle and lower leg. It can be harvested together with a vascularized split fibula segment, representing a simple alternative to several free composite flaps. Its complication rate can be lowered significantly if the proximal 3 cm of the muscle origin (i.e., the flap tip in distally pedicled flaps) is discarded during dissection and delicate hemostasis is performed.

Clavicula pro humero--a new surgical method for malignant tumors of the proximal humerus

In the majority of cases with malignant tumors in the proximal part of the humerus a limb saving tumor resection is possible. Reconstruction of the defect is necessary to maintain the length of the arm and to create a fulcrum for elbow flexion and extension. Several methods of reconstruction have been described in the literature including the fixation of distal humerus to the second rib or to the clavicle by means of Küntscher-nails, the implantation of a proximal humerus prosthesis without or with accompanying bone transplantation, a bridging of the defect using an allograft or an arthrodesis of the shoulder joint using free or vascularized bone transplants. The following paper describes a new surgical procedure whereby the vascularization of the clavicle is preserved and the clavicle used to bridge the defect. Although the follow-up period of the patients operated on so far in this way is relatively short, the functional advantages of this operation over the other forms of reconstruction can already be observed.

Transplantation of a vascularized rabbit femoral diaphyseal segment: Mechanical and histologic properties of a new living bone transplantation model

A new vascularized bone transplantation model is described, including the anatomy and surgical technique of isolating a rabbit femoral diaphyseal segment on its nutrient vascular pedicle. The histologic and biomechanical parameters of pedicled vascularized femoral autotransplants were studied following orthotopic reimplantation in the resulting mid-diaphyseal defect. Vascularized femur segments were isolated in 10 rabbits on their nutrient pedicle, and then replaced orthotopically with appropriate internal fixation. Postoperative weightbearing and mobility were unrestricted, and the contralateral femora served as no-treatment controls. After 16 weeks, the bone flaps were evaluated by x-ray (bone healing), mechanical testing (material properties), microangiography (quantification of intraosseous vasculature), histology (bone viability), and histomorphometry (bone remodeling). Bone healing occurred by 2 weeks, with further callus remodeling throughout the survival period. Eight transplants healed completely, while two had a distal pseudarthrosis. Microangiography demonstrated patent pedicles in all transplants. Intraosseous vessel densities were comparable to nonoperated (control) femora. We found ultimate strength and elastic modulus to be significantly reduced when compared to normal controls. Viable bone, increased mineral apposition rate, and bone turnover were demonstrated in all transplants. The method described, and the data provided will be of value for the further study of isolated segments of living bone, and in particular, for investigations of reconstruction of segmental bone loss in weight-bearing animal models. This study also provides important normative data on living autologous bone flap material properties, vascularity, and bone remodeling. We intend to use this method and data for comparison in subsequent studies of large bone vascularized allotransplantation.

Sequential Treatment with Intermittent Low-Dose Human Parathyroid Hormone (1-34) and Bisphosphonate Enhances Large-Size Skeletal Reconstruction by Vascularized Bone Transplantation

Vascularized bone transplantation enables reconstruction of large skeletal defects, but this process needs a long time. Since short-term intermittent parathyroid hormone (PTH) enhances rat fracture healing, we investigated the effects of 4-week intermittent low-dose (10 microg/kg/day) or high-dose (100 microg/kg/day) PTH followed by 4-week vehicle, low-dose or high-dose intermittent PTH, or zoledronic acid (ZOL, 2 micro/kg/week), a potent bisphosphonate, on large skeletal reconstruction by vascularized tibial grafting in rats. Compared to 8-week vehicle, 8-week low-dose PTH did not significantly increase the serum osteocalcin level as well as the urinary deoxypyridinoline level, while 4-week low-dose or high-dose PTH followed by 4-week ZOL decreased both of these levels. Eight-week PTH increased the bone mass of the graft and strength of the reconstructed skeleton in a dose-dependent manner; notably, the reconstructed skeleton showed an obviously higher response to PTH compared to the contralateral nonoperated femur. In contrast, 4-week PTH followed by 4-week vehicle reduced these effects and caused local bone loss at the host-graft junctions. Four-week PTH followed by 4-week ZOL did not induce such bone loss; however, 4-week high-dose PTH followed by 4-week ZOL caused a large callus in the distal cortical junction. Four-week PTH followed by 4-week ZOL increased the bone mass and strength similarly to 8-week PTH. These preliminary findings suggest, for the first time, that sequential treatment with short-term intermittent low-dose PTH and bisphosphonate as well as long-term intermittent low-dose PTH treatment enhance large skeletal reconstruction by vascularized bone transplantation, though early timing of sequential antiresorptive treatment could result in delay of bone repair.