Restoring Osteochondral Defects through the Differentiation Potential of Cartilage Stem/Progenitor Cells Cultivated on Porous Scaffolds

Cartilage stem/progenitor cells (CSPCs) are cartilage-specific, multipotent progenitor cells residing in articular cartilage. In this study, we investigated the characteristics and potential of human CSPCs combined with poly(lactic-co-glycolic acid) (PLGA) scaffolds to induce osteochondral regeneration in rabbit knees. We isolated CSPCs from human adult articular cartilage undergoing total knee replacement (TKR) surgery. We characterized CSPCs and compared them with infrapatellar fat pad-derived stem cells (IFPs) in a colony formation assay and by multilineage differentiation analysis in vitro. We further evaluated the osteochondral regeneration of the CSPC-loaded PLGA scaffold during osteochondral defect repair in rabbits. The characteristics of CSPCs were similar to those of mesenchymal stem cells (MSCs) and exhibited chondrogenic and osteogenic phenotypes without chemical induction. For in vivo analysis, CSPC-loaded PLGA scaffolds produced a hyaline-like cartilaginous tissue, which showed good integration with the host tissue and subchondral bone. Furthermore, CSPCs migrated in response to injury to promote subchondral bone regeneration. Overall, we demonstrated that CSPCs can promote osteochondral regeneration. A monophasic approach of using diseased CSPCs combined with a PLGA scaffold may be beneficial for repairing complex tissues, such as osteochondral tissue.

An Overview of the Application of Poly(lactic-co-glycolic) Acid (PLGA)-Based Scaffold for Drug Delivery in Cartilage Tissue Engineering

Poly(lactic-co-glycolic) acid (PLGA) has attracted a considerable amount of interest for biomedical application due to its biocompatibility, tailored biodegradation rate (depending on the molecular weight and copolymer ratio), approval for clinical use in humans by the U.S. Food and Drug Administration (FDA), the potential to change surface properties to create better interaction with biological materials and being suitable for export to countries and cultures where planting products with animals is unusable. For commercial use and research, PLGA has been widely studied to control small molecule drugs, proteins, and other macromolecules. This study aims to review the studies that used PLGA scaffolding and its composites as a scaffold and drug delivery in cartilage tissue engineering. It is concluded from the results that the PLGA scaffold as a synthetic scaffold, when combined with natural scaffolds or hybrids, strengthens its biological properties and performs its function better.

Design of PLGA-based Scaffolds for Developing and Differentiating Mesenchymal Stem Cells (MSCs)

In recent years, bone tissue engineering using cells, biomolecules, and scaffolds have made significant progress in the acute treatment of bone defects. In this study, a PLGA polymeric scaffold (40/60) was fabricated by solvent casting/salt leaching method using porogen (NaCl). The results of the structural analysis of the PLGA scaffold showed moderate porosity with pore sizes of 50 to 200 μm. Degradation of PLGA scaffold was found to be 80% for 80 hours as submerged in water. Water absorption by the scaffold was about 268.81% for 24 h of immersion. Cell biocompatibility tests showed optimal growth of LNCaP cell line on the scaffold. The growth and differentiation of MSCs on the scaffold occurred over a period of 21 days, which was confirmed by evaluating the expression of alkaline phosphatase (Alp) and osteopontin (Ops) genes. The amount of calcification of differentiated cells also confirmed the differentiation of MSCs into osteoblasts. Taken together, PLGA-based polymer scaffolds could potentially be used for tissue engineering, implant design, and drug delivery systems.

Beneficial Therapeutic Approach of Acellular PLGA Implants Coupled With Rehabilitation Exercise for Osteochondral Repair: A Proof of Concept Study in a Minipig Model

Background: Osteochondral (OC) repair presents a significant challenge to clinicians. However, whether the use of acellular spongy poly(lactic-co-glycolic acid) (PLGA) scaffolding plus treadmill exercise as a rehabilitation program regenerates OC defects in a large-animal model has yet to be determined. Hypothesis: PLGA scaffolding plus treadmill exercise may offer improved OC repair for both high and low weightbearing regions in a minipig model. Study Design: Controlled laboratory study. Methods: A total of 9 mature minipigs (18 knees) were randomly divided into the treadmill exercise (TRE) group or sedentary (SED) group. All pigs received critically sized OC defects in a higher weightbearing region of the medial condyle and a lower weightbearing region of the trochlear groove. In each minipig, a PLGA scaffold was placed in the defect of the right knee (PLGA subgroup), and the defect of the left knee was untreated (empty defect [ED] subgroup). The TRE group performed exercises in 3 phases: warm-up, 3 km/h for 5 minutes; main exercise, 4 km/h for 20 minutes; and cool-down, 3 km/h for 5 minutes. The total duration was about 30 minutes whenever possible. The SED group was allowed free cage activity. Results: At 6 months, the TRE-PLGA group showed the highest gross morphology scores and regenerated a smooth articular surface covered with new hyaline-like tissue, while the defects of the other groups remained and contained nontransparent tissue. Histologically, the TRE-PLGA group also revealed sound OC integration, chondrocyte-like cells embedded in lacunae, abundant glycosaminoglycans, a sound collagen structure, and modest inflammatory cells with an inflammatory response (ie, tumor necrosis factor–α, interleukin-6). In addition, in the medial condyle region, the TRE-PLGA group (31.80 ± 3.03) had the highest total histological scores (TRE-ED: 20.20 ± 5.76; SED-PLGA: 10.25 ± 6.24; SED-ED: 11.75 ± 6.50; P = .004). In the trochlear groove region, the TRE-PLGA group (30.20 ± 6.42) displayed significantly higher total histological scores (TRE-ED: 19.60 ± 7.00; SED-PLGA: 10.00 ± 5.42; SED-ED: 11.25 ± 5.25; P = .006). In contrast, the SED-PLGA and SED-ED groups revealed an irregular surface with abrasion, fibrotic tissue with an empty void and inflammatory cells, disorganized collagen fibers, and less glycosaminoglycan deposition. Micro–computed tomography analysis revealed that the TRE-PLGA group had integrated OC interfaces with continued remodeling in the subchondral bone. Furthermore, comparing the 2 defect regions, no statistically significant differences in cartilage regeneration were detected, indicating the suitability of this regenerative approach for both high and low weightbearing regions. Conclusion: Implanting an acellular PLGA scaffold plus treadmill exercise promoted articular cartilage regeneration for both high and low weightbearing regions in minipigs. Clinical Relevance: This study suggests the use of a cell-free porous PLGA scaffold and treadmill exercise rehabilitation as an alternative therapeutic strategy for OC repair in a large-animal knee joint model. This combined effect may pave the way for biomaterials and exercise regimens in the application of OC repair.

Coating Medpor® Implant with Tissue-Engineered Elastic Cartilage

Inert biomaterials used for auricular reconstruction, which is one of the most challenging and diverse tasks in craniofacial or head and neck surgery, often cause problems such as capsule formation, infection, and skin extrusion. To solve these problems, scaffold consisting of inert biomaterial, high-density polyethylene (Medpor®) encapsulated with neocartilage, biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) was created using a tissue engineering strategy. PLGA scaffold without Medpor® was created to serve as the control. Scaffolds were vacuum-seeded with rabbit chondrocytes, freshly isolated from the ear by enzymatic digestion. Then, cell-seeded scaffolds were implanted subcutaneously in the dorsal pockets of nude mice. After 12 weeks, explants were analyzed by histological, biochemical, and mechanical evaluations. Although the PLGA group resulted in neocartilage formation, the PLGA–Medpor® group demonstrated improved outcome with the formation of well-surrounded cartilage around the implants with higher mechanical strength than the PLGA group, indicating that Medpor® has an influence on the structural strength of engineered cartilage. The presence of collagen and elastin fibers was evident in the histological section in both groups. These results demonstrated a novel method of coating implant material with engineered cartilage to overcome the limitations of using biodegradable scaffold in cartilage tissue regeneration. By utilizing the patient’s own chondrocytes, our proposed method may broaden the choice of implant materials while minimizing side effects and immune reaction for the future medical application.