Abstract
Purpose
To perform a systematic review of postoperative rehabilitation protocols for third-generation autologous chondrocyte implantation (ACI) of the knee joint.
Methods
A systematic review was performed by searching PubMed, Cochrane Library, and EMBASE to locate randomized controlled trials that described a rehabilitation protocol following third-generation ACI of the knee joint. The search terms used were: “autologous” AND “chondrocyte” AND “randomized”. Data extracted from each study included various components of postoperative rehabilitation, such as initial weight-bearing (WB) status and time to full WB, the use of continuous passive motion (CPM), the time to return to sports, and physical therapy (PT) modalities used and the timing of their initiation.
Results
Twenty-five studies (22 Level I, 3 Level II) met inclusion criteria, including a total of 905 patients undergoing treatment with ACI. The average patient age ranged from 29.1 to 54.8 years, and the mean follow-up time ranged from 3 months to 10.0 years. The average lesion size ranged from 1.9 to 5.8 cm2, and the most common lesion location was the medial femoral condyle (n = 494). Twenty studies allowed partial WB postoperatively with all studies permitting full WB within 12 weeks. Twenty studies used CPM in their rehabilitation protocols and initiated its use within 24 hours postoperatively. Among 10 studies that reported time to return to sport, 9 (90%) allowed return by 12 months. While most protocols used strength training as well as the inclusion of proprioceptive training, there was disagreement on the timing and inclusion of specific PT modalities used during the rehabilitation process.
Conclusions
Based on the included studies, most rehabilitation protocols for third-generation ACI initiate CPM within 24 hours postoperatively and allow partial WB immediately following surgery with progression to full WB within 12 weeks. There is variation of the PT modalities used as well as the timing of their initiation.
Level of Evidence
Level II, systematic review of Level I-II studies.
Focal chondral defects (FCDs) of the knee joint can result in pain and swelling and may become especially disruptive to active patients and athletes.1 Cartilage defects are challenging to treat, given the avascularity of articular cartilage and the multiple factors that affect cartilage health, including meniscal status, limb alignment, and ligament stability.2 Current surgical treatments for FCDs of the knee joint include chondroplasty, microfracture (MFx), osteochondral autograft transfer (OAT), osteochondral allograft transplantation (OCA), and autologous chondrocyte implantation (ACI), among others.3 ACI, which is a 2-stage procedure, is now in its third-generation form, which is otherwise known as matrix-assisted ACI.4 Third-generation ACI involves taking a biopsy of healthy articular cartilage during the first-stage procedure, followed 6 to 8 weeks later by implantation of a matrix scaffold seeded with autologous chondrocytes.4
Given that third-generation ACI is a relatively novel procedure, postoperative rehabilitation following this procedure is not standardized.5 In a 2018 systematic review, Kraeutler et al.5 compared treatment failure rates and other clinical outcomes of matrix-assisted ACI based on the time to return to full weight-bearing (WB). However, this is just one aspect of postoperative rehabilitation, and other aspects, such as the use of continuous passive motion (CPM) and criteria for return-to-play (RTP), are equally important in determining a patient’s overall outcome and satisfaction. The purpose of this study was to perform a systematic review of postoperative rehabilitation protocols for third-generation ACI of the knee joint. The authors hypothesized that there would be heterogeneity in the postoperative rehabilitation protocols reported in the literature.
Methods
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Two independent reviewers (J.D., S.M.F.) searched PubMed, Embase, and the Cochrane Library up to January 17, 2022. The electronic search strategy used was: autologous AND chondrocyte AND randomized. A total of 652 studies were reviewed by title and/or abstract to determine study eligibility based on inclusion criteria. In cases of disagreement, a third reviewer (M.J.K.) made the final decision. Inclusion criteria included randomized controlled trials that reported their rehabilitation protocol after third-generation ACI for FCDs of the knee joint. Studies were excluded if they were nonrandomized, studies on first- or second-generation ACI, nonhuman studies, non-knee joint studies, the rehabilitation protocol was not reported, or no English full-text article was available. Data extraction from each study was performed independently by 2 authors (J.D., S.M.F.) and then reviewed by a third author (M.J.K.). There was no need for funding or a third party to obtain any of the collected data. Risk of bias was assessed according to the Cochrane Collaboration’s risk of bias tool,6 which incorporates an assessment of randomization, blinding, completeness of outcomes data, selection of outcomes reported, and other sources of bias.
Study Methodology Assessment
The Modified Coleman Methodology Score (MCMS)7 was used to evaluate study methodology quality. The MCMS has a scaled potential score ranging from 0 to 100. Scores ranging from 85 to 100 are excellent, 70 to 84 are good, 55 to 69 are fair, and less than 55 are poor. The primary outcomes assessed by the MCMS are study size and type, follow-up time, attrition rates, number of interventions per group, and proper description of study methodology.
Data Extraction
Data extracted from each study included the various components of postoperative rehabilitation, such as initial WB status and time to full WB, the use of CPM, the time to RTP, and physical therapy modalities used and the timing of their initiation.
Results
Twenty-five studies met inclusion and exclusion criteria (Fig 1), including a total of 905 patients undergoing treatment with ACI. The mean patient age ranged from 29.1 to 54.8 years and the mean follow-up ranged from 3 months to 10.0 years. The overall percentage of male subjects ranged from 44.4% to 74.2% and the mean body mass index ranged from 23.3 to 29.0 (Table 1). The mean lesion size ranged from 1.9 to 5.8 cm2. The most common lesion location was the medial femoral condyle (n = 494 cases) followed by the lateral femoral condyle (n = 167 cases). Six studies8, 9, 10, 11, 12, 13 presented 2 of the same patient populations and therefore only the studies with longer follow-up8,10,12 were included in the results of our systematic review.
Fig 1.
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. (ACI, autologous chondrocyte implantation.)
Table 1.
Patient Demographics
| Study | LOE | N | Male, % | Age at Surgery, y | BMI | Follow-up, y | Defect Size, cm2 | Lesion Location | Author Country | Type of ACI Product |
|---|---|---|---|---|---|---|---|---|---|---|
| Akgun et al., 201514 | I | 7 | 57 | 32.7 ± 10.4 | 24.3 ± 0.8 | 2 | 3.0 ± 0.8 | MFC: 5; LFC: 2 | Turkey | Chondro-Gide |
| Barié et al., 202015 | I | 9 | 44.4 | 30.4 ± 6.8 | 23.32 ± 1.15 | 9.6 ± 0.9 | 4.27 ± 0.2 | MFC: 8; LFC: 1 | Germany | BioSeed-C |
| Basad et al., 201016 | I | 40 | 63.0 | 33.0 | 25.3 | 2 | NR | C: 29; PT: 11 | Germany | ACI-Maix |
| Saris et al., 201411 Brittberg et al., 20188 |
I | 72 | 62.5 | 34.8 ± 9.2 | 26.2 ± 4.3 | 2 | 5.8 ± 5.1 | MFC: 48; LFC: 13; T: 4 | Netherlands/ Sweden | ACI-Maix |
| Clavé et al., 201617 | I | 30 | 66.7 | 29.2 ± 11.9 | 23.4 ± 3.1 | 2 | 3.1 ± 0.8 | NR | France | Cartipatch |
| Crawford et al., 201218 | I | 21 | 90.0 | 41 ± 9 | 29 ± 3 | 2 | 2.9 ± 1.4 | NR | U.S.A. | NeoCart |
| Ebert et al., 200824 | I | 62 | 64.5 | 38.3 | NR | 3 months | 3.3 | MFC: 45; LFC: 17 | Australia | ACI-Maix |
| Ebert et al., 201023 | I | 70 | 64.3 | 38.2 | NR | 2 | 3.3 | MFC: 52; LFC: 18 | Australia | ACI-Maix |
| Ebert et al., 201022 | I | 61 | 63.9 | 38.5 | NR | 1 | 3.3 | MFC: 46; LFC 15 | Australia | ACI-Maix |
| Ebert et al., 201120 | I | 69 | 63.8 | 38.2 | 26.6 | 2 | 3.3 | MFC: 52; LFC: 17 | Australia | ACI-Maix |
| Ebert et al., 201221 | I | 63 | 66.7 | 38.2 | 26.5 | 5 | 3.3 | MFC: 47; LFC: 16 | Australia | ACI-Maix |
| Ebert et al., 202019 | I | 60 | 65.0 | 37.6 | 27.5 | 10 | 3.27 | MFC: 44; LFC: 16 | Australia | ACI-Maix |
| Ebert et al., 202110 Ebert et al., 20179 |
I | 37 | 56.8 | 36.4 | 25.7 | 5 | 3.0 | MFC: 27; LFC: 10 | Australia | ACI-Maix |
| Edwards et al., 201325 | I | 28 | 60.7 | 35.8 | 25.6 | 1 | 2.9 | MFC: 20; LFC: 8 | Australia | ACI-Maix |
| Fossum et al., 201926 | II | 21 | 66.7 | 37.2 ± 10.8 | 25.7 ± 4.3 | 2 | 4.9 ± 4.4 | MFC: 7; LFC:2; T: 7; P: 1; PT: 2; T-MFC: 2 | Norway | Chondro-Gide |
| Hoburg et al., 202127 | I | 52 | 63.5 | 36 ± 10 | 25.7 ± 3.3 | 3 | 2.2 ± 0.7 | C: 52 | Germany | Spherox |
| Ibarra et al., 202128 | I | 24 | 70.8 | 33.7 ± 9.4 | 25.5 ± 3.1 | 6.2 ± 0.9 | 1.9 ± 0.9 | MFC: 7: LFC: 9; T: 1; P: 7 | Mexico | Neoveil |
| Liu et al., 202129 | I | 10 | 50 | 54.8 ± 18.0 | NR | 1.1 | 2.9 ± 0.8 | MFC: 10 | Taiwan | Kartigen |
| Niemeyer et al., 201931 | II | 52 | 63.4 | 36 ± 10 | 25.7 ± 3.3 | 2 | 2.2 ± 0.7 | C: 52 | Germany | Spherox |
| Niemeyer et al., 202030 | I | 75 | 70.7 | 33.5 ± 9.2 | 25.2 ± 3.1 | 4 | 5.0 ± 1.9 | C: 28; P: 47 | Germany | Spherox |
| Wondrasch et al 200913 Wondrasch et al. 201512 |
I | 31 | 74.2 | 33 | 24.7 | 2 | 4.8 | MFC: 22; LFC: 10 | Austria | HyalograftC |
| Zeifang et al., 201032 | II | 11 | 54.5 | 29.1 ± 7.5 | NR | 2 | 4.3 ± 1.1 | NR | Germany | BioSeed-C |
NOTE. Only the nonoverlapping patient samples are included to avoid redundancy. Sex is reported as a percentage. Age, BMI, follow-up, and defect size are reported as mean ± SD (if available).
ACI, autologous chondrocyte implantation; BMI, body mass index; C, nonspecified femoral condyle; LFC, lateral femoral condyle; LOE, Level of Evidence; MFC, medial femoral condyle; N, number of lesions; NR, not reported, P, patella; PT, patella-trochlea; SD, standard deviation; T, trochlea; T-MFC, trochlea and medial femoral condyle.
Postoperative WB
Twenty-two studies8,10,12,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 reported on postoperative WB (Table 2). All but 2 studies16,17 allowed partial WB immediately after operation. One study29 allowed full WB at 4 weeks, 9 studies10,12,15,18,25,26,28,30,32 allowed full WB at 6 weeks, 11 studies10,16,19, 20, 21, 22, 23, 24, 25,27,31 allowed full WB at 8 weeks, and 10 studies8,12,14,17,19, 20, 21, 22, 23, 24 allowed full WB at 10 to 12 weeks’ postoperatively. Three studies10,25,12 consisted of an initial 2-week period of WB at 20%, followed by a progressive increase to full WB at 6 weeks’ postoperatively. Eight studies10,19, 20, 21, 22, 23, 24, 25 consisted of a 2-week period of WB at 20%, with a progressive increase to full WB at 8 weeks’ postoperatively. One study12 described a 10-week rehabilitation protocol consisting of toe-touch WB for 4 weeks, followed by partial WB at 20% between weeks 4 and 6, 50% WB between weeks 6 and 8, and full WB by 10 weeks’ postoperatively. Five studies20, 21, 22, 23, 24 consisted of a 5-week period of WB at 20% with a progressive increase to full WB at 11 weeks’ postoperatively. One study19 consisted of a 2-week period of WB at 20%, with a progressive increase to full WB at 12 weeks’ postoperatively.
Table 2.
Postoperative WB
| Study | Initial WB Status | Progression to Full WB |
|---|---|---|
| Akgun et al., 201514 | Partial WB | 12 weeks |
| Barié et al., 202015 | Partial WB | 6 weeks |
| Basad et al., 201016 | Non-WB | 8 weeks |
| Brittberg et al., 20188 | Partial WB | 12 weeks |
| Clavé et al., 201617 | Non-WB | 10 weeks |
| Crawford et al., 201218 | Partial WB | 6 weeks |
| Ebert et al., 202019 | Partial WB | 8 weeks/12 weeks∗ |
| Ebert et al., 201120 | Partial WB | 8 weeks/11 weeks∗ |
| Ebert et al., 202110 | Partial WB | 6 weeks/8 weeks∗ |
| Ebert et al., 201221 | Partial WB | 8 weeks/11 weeks∗ |
| Ebert et al., 201022 | Partial WB | 8 weeks/11 weeks∗ |
| Ebert et al., 201023 | Partial WB | 8 weeks/11 weeks∗ |
| Ebert et al., 200824 | Partial WB | 8 weeks/11 weeks∗ |
| Edwards et al., 201325 | Partial WB | 6 weeks/8 weeks∗ |
| Fossum et al., 201926 | Partial WB | 6 weeks |
| Hoburg et al., 202127 | Partial WB | 8 weeks |
| Ibarra et al., 202128 | Partial WB | 6 weeks |
| Liu et al., 202129 | Partial WB | 4 weeks |
| Niemeyer et al., 202030 | Partial WB | 6 weeks |
| Niemeyer et al., 201931 | Partial WB | 8 weeks |
| Wondrasch et al., 201512 | Partial WB | 6 weeks/10 weeks∗ |
| Zeifang et al., 201032 | Partial WB | 6 weeks |
WB, weight-bearing.
These studies compared return to full WB at 2 different time points.
Continuous Passive Motion
Eighteen studies10,12,14, 15, 16,18, 19, 20, 21,23, 24, 25, 26, 27, 28,30, 31, 32 used CPM as part of the rehabilitation process for all patients included (Table 3). In most studies, CPM was initiated within 12 to 24 hours of surgery with an initial range of motion (ROM) of 0 to 30° of knee flexion.
Table 3.
Continuous Passive Motion (CPM)
| Study | Initiation of CPM (Postoperatively) | Initial ROM | Duration of CPM |
|---|---|---|---|
| Akgun et al., 201514 | 12-24 hours | 0°-30° | 1 hour/NR |
| Barié et al., 202015 | 24 hours | NR | NR/6 weeks |
| Basad et al., 201016 | NR | NR | NR |
| Crawford et al., 201218 | 24 hours | NR | NR |
| Ebert et al., 202019 | NR | 0°–30° | NR |
| Ebert et al., 201120 | NR | 0°–30° | NR/3 weeks |
| Ebert et al., 202110 | 12-24 hours | 0°–30° | 1 hour/NR |
| Ebert et al., 201221 | 12-24 hours | 0°–30° | NR |
| Ebert et al., 201023 | 12-24 hours | 0°–30° | NR |
| Ebert et al., 200824 | 12-24 hours | 0°–30° | 1 hour/NR |
| Edwards et al., 201325 | 12-24 hours | 0°–30° | 1 hour/NR |
| Fossum et al., 201926 | NR | NR | 4 hours/5 days |
| Hoburg et al., 202127 | 24 hours | 0°–60° | NR/6 weeks |
| Ibarra et al., 202128 | 72 hours | 0°–40° | 4 hours/NR |
| Niemeyer et al., 202030 | 24 hours | 0°–60° | NR/6 weeks |
| Niemeyer et al., 201931 | 24 hours | 0°–60° | NR/6 weeks |
| Wondrasch et al., 201512 | 48 hours | 0°–40° | 3 hours/NR |
| Zeifang et al., 201032 | 24 hours | NR | NR/6 weeks |
NOTE. Duration of CPM values are reported as hours per day/total number of days or weeks that CPM was used.
NR, not reported; ROM, range of motion.
Return-to-Play
Ten studies8,10,15,18,21,27,28,30, 31, 32 reported on the time to RTP following surgery. In 9 studies,8,10,15,21,27,28,30, 31, 32 RTP was allowed at 12 months after ACI. In one study,18 sports activity was allowed after 6 months.
Physical Therapy
Thirteen studies8,10,12,19, 20, 21,23, 24, 25,27,28,30,31 used isometric exercises as part of their postoperative rehabilitation protocol (Table 4). Ten studies10,17,20, 21, 22, 23, 24, 25, 26,28 described the use of a brace during rehabilitation. Thirteen studies8,10,12,17,20,21,25, 26, 27, 28, 29, 30, 31 stated time to full knee ROM. Three studies10,21,28 described the use of open-chain exercises. Four studies10,20,21,25 described the use of closed-chain exercises, with all 4 studies initiating these exercises at 7 weeks postoperatively. Thirteen studies8,10,12,19, 20, 21,23, 24, 25, 26, 27,30,31 described the use of progressive strengthening in their rehabilitation protocol. Eight studies8,10,20,21,25,27,30,31 described the use of neuromuscular (proprioceptive/balance) training. Eight studies8,10,20,21,25,27,30,31 addressed initiation of sports-specific movements. Eight studies10,14,19, 20, 21,23, 24, 25 used cryotherapy to control edema.
Table 4.
Rehabilitation Protocols
| Study | Isometric Exercise | Brace Duration | Time to Full ROM | Open-Chain Exercises | Closed-Chain Exercises | Progressive Strengthening | Neuromuscular Training | Sports-Specific Movements |
|---|---|---|---|---|---|---|---|---|
| Brittberg et al., 20188 | NR | – | 12 | – | – | 6 | 12 | 12 |
| Clavé et al., 201617 | – | 4 | 10 | – | – | – | – | – |
| Ebert et al., 202019 | NR | – | – | – | – | NR | – | – |
| Ebert et al., 201120 | 1 | 12 | 5 | – | 7 | 4 | 7 | 7 |
| Ebert et al., 202110 | 1 | 12 | 5 | 12 | 7 | 4 | 7 | 7 |
| Ebert et al., 201221 | 1 | 12 | 7 | 12 | 7 | 7 | 7 | 7 |
| Ebert et al., 201022 | – | 12 | – | – | – | – | – | – |
| Ebert et al., 201023 | NR | 12 | – | – | – | NR | – | – |
| Ebert et al., 200824 | NR | 11 | – | – | – | NR | – | – |
| Edwards et al., 201325 | 1 | 8 | 5 | – | 7 | 4 | 7 | 7 |
| Fossum et al., 201926 | – | 6 | NR | – | – | NR | – | – |
| Hoburg et al., 202127 | NR | – | 7 | – | – | 7 | 7 | 7 |
| Ibarra et al., 202128 | 1 | 6 | 6 | 16 | – | – | – | – |
| Liu et al., 202129 | – | – | 3 days | – | – | – | – | – |
| Niemeyer et al., 202030 | 1 | – | 7 | – | – | 7 | 7 | 7 |
| Niemeyer et al., 201931 | 1 | – | 7 | – | – | 7 | 7 | 7 |
| Wondrasch et al., 201512 | 1 | – | 4 | – | – | 6 | – | – |
NOTE. Values are reported as time of initiation following surgery (in weeks unless otherwise specified). Brace duration is reported as total number of weeks of brace use.
NR, study reported use of regimen but did not specify initiation time; ROM, range of motion; –, rehab modality was not mentioned.
Modified Coleman Methodology Score
Table 5 shows the MCMS scores from the 25 included studies. Six studies10,20,21,28,30,31 received an excellent score, 17 studies8,9,11, 12, 13, 14, 15, 16, 17, 18, 19,22, 23, 24,27,29,32 received a good score, and 2 studies25,26 received a fair score.
Table 5.
Modified Coleman Methodology Score (MCMS)
| Study | MCMS |
|---|---|
| Akgun et al., 201414 | 75 |
| Barie et al., 202015 | 76 |
| Basad et al., 201016 | 82 |
| Brittberg et al., 20188 | 81 |
| Clavé et al., 201617 | 82 |
| Crawford et al., 201218 | 79 |
| Ebert et al., 201221 | 91 |
| Ebert et al., 202110 | 88 |
| Ebert et al., 201120 | 85 |
| Ebert et al., 20179 | 82 |
| Ebert et al., 202019 | 82 |
| Ebert et al., 201023 | 81 |
| Ebert et al., 201022 | 80 |
| Ebert et al., 200824 | 80 |
| Edwards et al., 201325 | 69 |
| Fossum et al., 201926 | 69 |
| Hoburg et al., 202027 | 80 |
| Ibarra et al., 202128 | 85 |
| Liu et al., 202129 | 70 |
| Niemeyer et al., 201931 | 88 |
| Niemeyer et al., 202030 | 85 |
| Saris et al., 201411 | 78 |
| Wondrasch et al., 200913 | 82 |
| Wondrasch et al., 201512 | 81 |
| Zeifang et al., 201032 | 75 |
Methodologic Quality Assessment
The results of the methodologic quality assessment of included studies using the Cochrane Collaboration’s risk of bias tool are presented in Figure 2. Sequence generation and allocation were adequately reported by most studies,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,27,30, 31, 32 except in 4 studies,8,26,28,29 in which the concealment of allocation from the investigators was unclear (unclear risk of bias). Fourteen studies9, 10, 11, 12, 13, 14, 15,17, 18, 19, 20, 21,30,31 were deemed to be at low risk for detection bias because of the blinding of the outcome assessor, whereas 11 studies8,16,22, 23, 24, 25, 26, 27, 28, 29,32 did not use blinded outcome assessors (high risk of bias). Due to the nature of the study, all patients in all studies were aware of which treatment group they were in (high risk of bias). Three studies26,31,32 reported a minor loss of follow-up between 10 and 20% without proper explanation (unclear risk of bias), while no other studies reported significant loss of follow-up (low risk of bias).
Fig 2.
Risk of bias graph. Risk of bias is presented as a percentage across all included studies (green, low risk; yellow, unclear; red, high risk).
Discussion
The principal finding of this study was that most studies on third-generation ACI allowed partial WB postoperatively, with all studies progressing to full WB by 12 weeks following surgery. CPM was described in 20 studies and often initiated within 24 hours following the ACI procedure. Most studies allowed a full RTP at 12 months postoperatively. While most protocols used strength training as well as the inclusion of proprioceptive training, there was disagreement on the timing and inclusion of specific physical therapy modalities used during the rehabilitation process. In comparison, MACI (Vericel, Cambridge, MA) has published its own rehabilitation protocol.33 Patients are mobile with crutches within the first week, and obtain full WB and full knee ROM without a knee brace by 8 to 12 weeks’ postsurgery. Isometric exercises are started within 1 to 2 weeks, and sports-like movement and balancing exercises are initiated by 4 weeks. Patients can expect full RTP activity by 9 months. The evidence behind this protocol has been described in detail in one study.34 The first 6 weeks allow for implantation and protection, the next 6 weeks allow for transition and proliferation, with the subsequent 14 weeks allowing for remodeling and maturation. Ten studies8,10,16,19, 20, 21, 22, 23, 24, 25 followed the Vericel protocol.
Third-generation ACI has garnered significant attention in recent years based on its advantages of using autologous chondrocytes in a scaffold that may be cut to the precise shape of a focal defect. A recent systematic review35 demonstrated superior outcomes with third-generation ACI compared with MFx, despite a previous systematic review36 (which included first- and second-generation ACI) showing no outcome differences between ACI and MFx. Furthermore, although ACI is typically considered a second-line treatment option due to its greater cost compared with other cartilage repair options,3 recent evidence has shown that primary ACI results in improved outcomes compared with ACI following failed marrow stimulation techniques.37 This lends further credence to the thought of ACI as another first-line treatment option for FCDs. Given the increasing popularity of third-generation ACI, it is important to attempt to standardize the various aspects of perioperative care for these patients, in particular postoperative rehabilitation.
In a 2018 systematic review of 7 randomized controlled trials, Kraeutler et al.5 compared failure rates and patient-reported outcomes between patients undergoing third-generation ACI based on the time to return to full WB (6, 8, or 10/11 weeks). The authors found no significant differences in treatment failure rates between groups at a mean follow-up of 2.5 years, with significant improvements in Knee Injury and Osteoarthritis Outcome Scores, Short-Form Health Survey, and visual analog scale scores within each group. The present study builds upon this previous systematic review by reviewing additional features of postoperative rehabilitation such as the use of CPM devices and return to sport criteria.
In the basic science literature, cyclical articular joint loading has been shown to strengthen cartilage at the tissue and cellular level by increasing the amount of proteoglycan in the cartilage as well as promoting neochondrogenesis to significantly improve cartilage quality and knee motion.38,39 Furthermore, CPM may increase synovial fluid movement and joint surface articulation to help offset the complications that result from non–weight-bearing as well as affecting the nutritional transport system of the knee.40,41 Despite the benefits illustrated by animal models, clinical evidence is lacking in quality and homogeneity to support implementation of CPM following cartilage restoration procedures. One systematic review assessed the use of CPM following cartilage repair procedures and found that the majority of studies did not describe common variables such as the duration of CPM therapy, the initiation timing of CPM therapy, and the initial ROM used.42 The review found only 4 studies that directly examined the effect of CPM on postoperative results. In an animal model, one study43 compared the effects of CPM and immobilization on synovitis and cartilage degeneration. The study found that in the CPM group, there was greater synovitis at 2 weeks, but at 6 weeks articular cartilage was preserved in the knees treated with CPM compared to immobilization.
In comparison, a previous systematic review44 evaluated the rehabilitation protocols, RTP guidelines, and subsequent rates of RTP following MFx, OAT, OCA, and ACI. The study found that the majority of patients were able to RTP following cartilage restoration procedures in the knee, regardless of surgical procedure used. However, while the rate of RTP at the same level was similar to the overall rate of return following OAT, there was a large number of patients unable to return to the same level following MFx, OCA, and ACI. In addition, there was wide variety in the rehabilitation protocols, and scant literature on RTP protocols.
Limitations
The limitations of this study should be noted. There was heterogeneity in the third-generation ACI products used, the various aspects of postoperative rehabilitation across studies, patient groups, and lesion size. Furthermore, this study used stringent inclusion criteria, which limits generalizability. Also, the majority of the studies came from the same author groups, with several studies published by the same research team, which may have skewed the results. Lastly, the rehabilitation protocols found in scientific studies designed to control various characteristics might not be reflective of what occurs in a clinical setting outside of a research protocol.
Conclusions
Based on the included studies, most rehabilitation protocols for third-generation ACI initiate CPM within 24 hours postoperatively and allow partial WB immediately following surgery with progression to full WB within 12 weeks. There is variation of the PT modalities used as well as the timing of their initiation.
Footnotes
The authors report the following potential conflicts of interest or sources of funding: P.C.M. reports consultant for Arthrex and research support from Smith & Nephew, outside the submitted work. A.J.S. reports consultant for Mitek; stock/stock options from Biomet, CONMED Linvatec, Johnson & Johnson, Pfizer, Smith & Nephew, and Stryker; and research support from Isto Biologics, outside the submitted work. Full ICMJE author disclosure forms are available for this article online, as supplementary material.
Supplementary Data
References
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