Continuous Passive Motion Promotes and Maintains Chondrogenesis in Autologous Endothelial Progenitor Cell-Loaded Porous PLGA Scaffolds during Osteochondral Defect Repair in a Rabbit Model

Wang, Hsueh Chun; Lin, Tzu Hsiang; Chang, Nai-Jen; Hsu, Hsiang‐Chen; Yeh, Ming Long

doi:10.3390/ijms20020259

Cited by 11 publications

(12 citation statements)

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“…Previous animal studies have demonstrated the benefit of CPM use with improved chondrogenesis and reduced cartilage breakdown; however, there is a general lack of clinical data available to support this. 20,38,66,76 The studies evaluated predominantly used time-based protocols, with very few utilizing measurements or patient-specific metrics as checkpoints for progression. RTP timelines were reported inconsistently, and there was notable variation within the reported timelines.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The majority of studies had a timeline cutoff for removal of the brace, but 5 (8.1%) studies reported objective criteria for brace removal. 16,27,60,62,76 The objective criterion noted in all 5 studies was the return of quadriceps strength. This The Orthopaedic Journal of Sports Medicine Return-to-Play Criteria After OCA 3 was evaluated by the patient's ability to perform a straight leg raise without an extension lag as well as the demonstration of quadriceps strength adequate to support ambulation.…”

Section: Bracingmentioning

confidence: 99%

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Rehabilitation and Return-to-Play Criteria After Fresh Osteochondral Allograft Transplantation: A Systematic Review

Stark

Rao

Gleason

et al. 2021

Orthopaedic Journal of Sports Medicine

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Background: Fresh osteochondral allograft (OCA) is a treatment option that allows for the transfer of size-matched allograft cartilage and subchondral bone into articular defects of the knee. Although long-term studies show good functional improvement with OCA, there continues to be wide variability and a lack of consensus in terms of postoperative rehabilitation protocols and return to sport. Purpose: To systematically review the literature and evaluate the reported rehabilitation protocols after OCA of the knee, including weightbearing and range of motion (ROM) restrictions as well as return-to-play criteria. Study Design: Systematic review; Level of evidence, 4. Methods: PubMed, EMBASE, Cumulative Index of Nursing Allied Health Literature, SPORTDiscus, and Cochrane databases were searched according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies on knee OCA. Studies were included if they reported return-to-play data or postsurgical rehabilitation protocols. Results: A total of 62 studies met the inclusion criteria, with a total of 3451 knees in 3355 patients. Concomitant procedures were included in 30 of these studies (48.4%). The most commonly cited rehabilitation protocols included weightbearing restrictions and ROM guidelines in 100% and 90% of studies, respectively. ROM was most commonly initiated within the first postoperative week, with approximately half of studies utilizing continuous passive motion. Progression to weightbearing as tolerated was reported in 60 studies, most commonly at 6 weeks (range, immediately postoperatively to up to 1 year). Of the 62 studies, 37 (59.7%) included an expected timeline for either return to play or return to full activity, most commonly at 6 months (range, 4 months to 1 year). Overall, 13 studies (21.0%) included either objective or subjective criteria to determine return to activity within their rehabilitation protocol. Conclusion: There is significant heterogeneity for postoperative rehabilitation guidelines and the return-to-play protocol after OCA of the knee in the literature, as nearly half of the included studies reported use of concomitant procedures. However, current protocols appear to be predominantly time-based without objective criteria or functional assessment. Therefore, the authors recommend the development of objective criteria for patient rehabilitation and return-to-play protocols after OCA of the knee.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Bracingmentioning

confidence: 99%

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Rehabilitation and Return-to-Play Criteria After Fresh Osteochondral Allograft Transplantation: A Systematic Review

Stark

Rao

Gleason

et al. 2021

Orthopaedic Journal of Sports Medicine

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“…16-19 For instance, animal studies using continuous passive have shown earlier resumption of ROM results in improved chondrogenesis, proteoglycan and glycosaminogen synthesis in cartilage as well as decreasing collagen breakdown. 17,20,21 Additionally, early ROM prevents disuse atrophy and prevents knee stiffness, which improve early postoperative outcomes. 22 However, it remains to be seen clinically whether early resumption of ROM is superior to providing a limited-flexion brace, which is claimed to prevent shear forces in the early postoperative phase.…”

Section: Discussionmentioning

confidence: 99%

Return-to-Play and Rehabilitation Protocols following Cartilage Restoration Procedures of the Knee: A Systematic Review

et al. 2019

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Objective The purpose of this study is to systematically review the literature and to evaluate the reported rehabilitation protocols, return-to-play guidelines, and subsequent rates of return to play following cartilage restoration procedures in the knee. Design MEDLINE, EMBASE, and the Cochrane Library were searched according to the PRISMA guidelines to find studies on cartilage restoration procedures in the knee, including (1) microfracture (Mfx), (2) osteochondral autograft transfer (AOT), (3) osteochondral allograft implantation (OCA), and (4) autologous chondrocyte implantation (ACI). Studies were included if they reported return-to-play data or rehabilitation protocols. Results Overall, 179 studies fit our inclusion criteria, with 48 on Mfx, 34 on AOT, 54 on OCA, and 51 on ACI. The rate of return to play was reported as high as 88.2% with AOT, and as low as 77.2% following OCA, with rates of return to play at the same/higher level as high as 79.3% with AOT, and as low as 57.3% following ACI. The average reported time of return to play was as low as 4.9 months with AOT, and as high as 11.6 months following ACI. Conclusions The majority of patients are able to return to play following cartilage restoration procedures in the knee, regardless of surgical procedure utilized. However, while the rate of return to play at the same level was similar to the overall rate of return following AOT, there was a large number of patients unable to return to the same level following Mfx, OCA, and ACI. Additionally, there is wide variety in the rehabilitation protocols, and scant literature on return-to-play protocols.

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“…This implant creates a temporary shell for tissue regeneration in osteochondral (OC) defects in the knee joint. 4,34 Furthermore, PLGA has been approved by the US Food and Drug Administration for use as a biomaterial in medical devices in preclinical trials 3,31,35,39 and in the clinical orthopaedic setting, indicating that bench research translates to clinical applications. 36 Appropriate mechanical stimuli (eg, physical therapy exercises) provide joint homeostasis in the anabolic and catabolic cytokines of chondrocytes and directly affect the hyaline cartilage repair process.…”

mentioning

confidence: 99%

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

et al. 2020

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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.

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Continuous Passive Motion Promotes and Maintains Chondrogenesis in Autologous Endothelial Progenitor Cell-Loaded Porous PLGA Scaffolds during Osteochondral Defect Repair in a Rabbit Model

Cited by 11 publications

References 56 publications

Rehabilitation and Return-to-Play Criteria After Fresh Osteochondral Allograft Transplantation: A Systematic Review

Rehabilitation and Return-to-Play Criteria After Fresh Osteochondral Allograft Transplantation: A Systematic Review

Return-to-Play and Rehabilitation Protocols following Cartilage Restoration Procedures of the Knee: A Systematic Review

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

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