Gelatin-based resorbable sponge as a carrier matrix for human mesenchymal stem cells in cartilage regeneration therapy.

Adult mesenchymal stem cells (MSCs), found in the bone marrow, have the potential to differentiate into multiple connective tissue types, including cartilage. In this study, we examined the potential of a porous gelatin sponge, Gelfoam, for use as a delivery vehicle for MSCs in cartilage regeneration therapy. Adult human MSCs (hMSCs) were seeded throughout the gelatin sponge after a 2-h incubation period. When cultured for 21 days in vitro in a defined medium supplemented with 10 ng/mL of TGF-beta 3, hMSC/Gelfoam constructs produced a cartilage-like extracellular matrix containing sulfated glycosaminoglycans (s-GAGs) and type-II collagen, as evident upon histologic evaluation. Constructs loaded with a cell suspension of 12 x 10(6) cells/mL produced an extracellular matrix containing 21 microg of s-GAG/microg of DNA after 21 days of culture. This production was more efficient than constructs loaded at higher or lower cell densities, indicating that the initial seeding density influences the ability of cells to produce extracellular matrix. When implanted in an osteochondral defect in the rabbit femoral condyle, Gelfoam cylinders were observed to be very biocompatible, with no evidence of immune response or lymphocytic infiltration at the site. Based on these observations we conclude that Gelfoam resorbable gelatin sponge is a promising candidate as a carrier matrix for MSC-based cartilage regeneration therapies.

Fabrication of controlled release biodegradable foams by phase separation.

Highly porous biodegradable foams with controlled release function were fabricated by a phase separation technique. This technique involved inducing phase changes in a homogeneous solution of polymers with naphthalene or phenol used as solvents. A variety of foams with pore sizes ranging from 20 to 500 microm were made of poly(L-lactic acid) (PLLA), poly(bisphenol A-phenylphosphonate (BPA/PP), and its copolymer with poly[bis(2-ethoxy)- hydrophosphonic terephthalate] (PP/PPET). Controlled delivery capability was demonstrated by studying the release of sulforhodamine B and alkaline phosphatase (AP) from these highly porous structures. After an initial burst, AP was released from BPA/PP and PLLA foams at a near steady rate of 0.32 +/- 0.04 and 0.49 +/- 0.13 mg/day/g foam, respectively. These foams were intended for use as cell transplantation devices and tissue grafts such as synthetic bone grafts. Hydroxyapatite (HA) was added into the foams in an attempt to enhance interaction of these foams with bone. This composite was analyzed by energy dispersive spectroscopy, differential scanning calorimetry, and thermomechanical analysis. Since phosphates are known to have good affinity to calcium, poly(phosphoester) foams were treated with 1M calcium chloride solution in an attempt to study the possible interaction of the degrading poly(phosphoester) with calcium. After three weeks in 1 M calcium chloride solution, the complex modulus of the poly(phosphoester) foams changed from 40 to 1948 kPa, with a concurrent decrease in loss tangent from 0.349 to 0.170.