Enzo Caruso

Recapitulation of signals regulating embryonic bone formation during postnatal growth and in fracture repair

A number of proteins have recently been identified which play roles in regulating bone development. One important example is Indian hedgehog (Ihh) which is secreted by the prehyprtrophic chondrocytes. Ihh acts as an activator of a second secreted factor, parathyroid hormone-related protein (PTHrP), which, in turn, negatively regulates the rate of chondrocyte differentiation. Here we examine the expression of these genes and their molecular targets during different stages of bone development. In addition to regulating PTHrP expression in the perichondrium, we find evidence that Ihh may also act on the chondrocytes themselves at particular stages. As bone growth continues postnatally in mammals and the developmental process is reactivated during fracture repair, understanding the molecular basis regulating bone development is of medical relevance. We find that the same molecules that regulate embryonic endochondral ossification are also expressed during postnatal bone growth and fracture healing, suggesting that these processes are controlled by similar mechanisms.

Meniscal repair using engineered tissue

In this study, devitalized meniscal tissue pre‐seeded with viable cultured chondrocytes was used to repair a bucket‐handle incision in meniscal tissue transplanted to nude mice. Lamb knee menisci were devitalized by cyclic freezing and thawing. Chips measuring four by two by one‐half millimeters were cut from this devitalized tissue to serve as scaffolds. These chips were then cultured either with or without viable allogeneic lamb chondrocytes. From the inner third of the devitalized meniscal tissue, rectangles were also cut approximately 8 × 6 mm. A 4 mm bucket‐handle type incision was made in these blocks. The previously prepared chips either with (experimental group) or without viable chondrocytes (control group) were positioned into the incisions and secured with suture. Further control groups included blocks of devitalized menisci with incisions into which no chips were positioned and either closed with suture or left open with no suture. Specimens were transplanted to subcutaneous pouches of nude mice for 14 weeks. After 14 weeks, seven of eight experimental specimens (chips with viable chondrocytes) demonstrated bridging of the incision assessed by gross inspection and manual distraction. All the control groups were markedly different from the experimental group in that the incision remained grossly visible. Histological analysis was consistent with the differences apparent at the gross level. Only the experimental specimens (chips with viable chondrocytes) with gross bridging demonstrated obliteration of the interface between incision and scaffold. None of the control specimens revealed any cells or tissue filling the incision. Tissue engineering using scaffolds and viable cells may have an application in meniscal repair in vivo.

Heterotopic Ossification Around the Elbow Following Burns in Children: Results After Excision

BACKGROUND Major burn injuries close to joints alter the function of the musculoskeletal system through tissue loss and limitation of joint motion. In children with involvement of the hand, wrist, and forearm, restriction of elbow motion secondary to heterotopic ossification following a burn injury severely limits the function of the upper extremity. The purpose of this study was to review elbow function following excision of heterotopic ossification around the elbow in children. METHODS Eight children (ten elbows) from a population of 3245 consecutive patients who were admitted to our pediatric burn center were found to have severe heterotopic ossification of the elbow, leading to an inability to reach the mouth for feeding and the head and the perineum for self-care. Excision of the heterotopic ossification was undertaken if the patient had this limitation of function and if movement was restricted to a total arc of motion of <50 degrees. Pain was not an indication for the operation. The procedure was performed at an average of 17.3 months following the injury. RESULTS Seven children (nine elbows) were available for follow-up at an average of fifty-six months after surgery. All nine elbows had an improved arc of motion (an average increase of 57 degrees ). Following excision, heterotopic ossification did not recur. All children were able to reach the face and the perineum following the operation. CONCLUSIONS Excision of heterotopic ossification around the elbow following a burn injury in children can improve the arc of motion and improve the function of the extremity. A relatively simple operative and postoperative regimen can achieve satisfactory results.